Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study.

# Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study *The Lancet 2026* Articles Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study M Lia Palomba, Stephen J Schuster, Reem Karmali, Alan P Skarbnik, Jeremy S Abramson, Kirit Ardeshna, Peter Borchmann, Brian T Hill, Alejandro Martin García-Sancho, Gianpaolo Marcacci, Aaron P Rapoport, Guillaume Cartron, Isabelle Fleury, Koji Izutsu, Manali Kamdar, Stephan Mielke, Anna Maria Barbui, Juan Luis Reguera Ortega, Loretta J Nastoupil, Sairah Ahmed, Merav Bar, Lizbeth Diaz, Ulrika Furustrand, Victoria Diab, Min Vedal, Ariel Avilion, Jinender Kumar, Rina Nishii, Silvia Colicino, Franck Morschhauser Summary Background Eective treatments with deep and durable responses for relapsed or refractory marginal zone lymphoma Lancet 2026; 407: 963–75 (MZL) are lacking. The objective of the primary analysis from the MZL cohort of TRANSCEND FL was to evaluate the Published Online ecacy and safety of the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel. February 12, 2026 https://doi.org/10.1016/ S0140-6736(25)02435-3 Methods In this phase 2, single-arm, multicohort study, patients from 30 sites in the USA, Canada, Europe, and Japan See Comment page 917 with relapsed or refractory MZL who had at least two previous lines of systemic therapy were eligible to receive Memorial Sloan Kettering lisocabtagene maraleucel (100 × 10⁶ CAR+ T cells). Bridging therapy was allowed. The primary endpoint was overall Cancer Center, New York, NY, response rate per independent review committee by CT by use of Lugano 2014 criteria (null hypothesis ≤50%). This USA (Prof M L Palomba MD); study is registered with ClinicalTrials.gov, NCT04245839, and is ongoing. Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Findings Of 77 leukapheresed patients recruited between November 11, 2020, and August 24, 2023, 67 received Philadelphia, PA, USA lisocabtagene maraleucel and 66 were ecacy evaluable. MZL subtypes included nodal (n=32 [48%]), splenic (Prof S J Schuster MD); (n=18 [27%]), and extranodal–mucosa-associated lymphoid tissue (n=17 [25%]). Median (IQR) previous lines of Northwestern University systemic therapy was 3 (2–4). Median on-study follow-up was 24·1 months. The primary endpoint was met, with an Feinberg School of Medicine, Robert H Lurie Comprehensive overall response rate of 95% (n=63; 95% CI, 87·3–99·1; one-sided p<0·0001). All patients experienced a treatment- Cancer Center, Chicago, IL, USA related adverse event. Grade 3 cytokine release syndrome or neurological events occurred in three (4%) patients each (R Karmali MD); Novant Health (no grade 4–5 events). 11 (16%) patients had grade ≥3 infections: six (9%) patients during the 90-day treatment- Cancer Institute, Charlotte, NC, emergent period and seven (10%) during the post-treatment-emergent period. USA (A P Skarbnik MD); Lymphoma Program, Massachusetts General Interpretation In patients with relapsed or refractory MZL, lisocabtagene maraleucel showed high rates of durable Hospital Cancer Center, responses. The safety profile was manageable, with no new safety signals. These results support lisocabtagene Harvard Medical School, maraleucel as a new treatment option for patients with relapsed or refractory MZL. Boston , MA, USA (Prof J S Abramson MD); University College London Funding Celgene, a Bristol-Myers Squibb Company. Hospitals Biomedical Research Centre, London, UK Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar (K Ardeshna MD); Universität zu Köln, Albertus-Magnus-Platz, technologies. Cologne, Germany (Prof P Borchmann MD); Introduction (eg, zanubrutinib), can be used to treat MZL from first Cleveland Clinic, Cleveland, OH, Marginal zone lymphoma (MZL) is an indolent B-cell relapse,8,9 patients with relapsed or refractory MZL in USA (B T Hill MD); Hospital Universitario de Salamanca, malignancy that accounts for 7% of mature non-Hodgkin their third line or later of therapy represent a high-risk IBSAL, CIBERONC, Universidad lymphomas.1–4 MZL is characterised by slow growth, and subset of patients for whom more eective therapies de Salamanca, Salamanca, it does not always require immediate therapy. A with deep and durable responses are needed.2 Spain (A M García-Sancho MD); National Cancer Institute, proportion of patients will eventually require treatment, Promising outcomes have been observed with Fondazione ‘G Pascale’, IRCCS, which typically includes a CD20 monoclonal antibody as axicabtagene ciloleucel chimeric antigen receptor (CAR) Naples, Italy (G Marcacci MD); first-line therapy. Although patients with MZL generally T-cell therapy in patients with relapsed or refractory MZL University of Maryland respond to initial treatment, repeated relapses are (n=31) in the third line or later setting.10 Nevertheless, Marlene and Stewart Greenebaum Comprehensive common.2 Patients with progression of disease up to this therapy is not approved for the treatment of relapsed Cancer Center, Baltimore, MD, 24 months (POD24) after diagnosis or initial treatment or refractory MZL, is associated with considerable USA (Prof A P Rapoport MD); have inferior outcomes, with higher risk of disease toxicity, and its ecacy in splenic MZL was not evaluated Montpellier University Hospital transformation and shorter survival.2,5–7 Although some in the ZUMA-5 study. Center, UMR CNRS, Montpellier, France systemic therapies, including lenalidomide plus Lisocabtagene maraleucel, an autologous, CD19- (Prof G Cartron MD); Hôpital rituximab (R²) and Bruton tyrosine kinase inhibitors directed, 4-1BB CAR T-cell product, has previously shown Maisonneuve–Rosemont, Articles Montreal, QC, Canada Research in context (I Fleury MD); National Cancer Center Hospital, Chuo City, Evidence before this study patients with relapsed or refractory MZL to date. The study Tokyo, Japan (K Izutsu MD); University of Colorado Cancer We searched PubMed for clinical studies published from included patients with all three subtypes of MZL (nodal, Center, Aurora, CO, USA March 20, 2005, to March 20, 2025, using the terms “chimeric extranodal–mucosa-associated lymphoid tissue, and splenic). In (M Kamdar MD); Departments antigen receptor” and “marginal zone lymphoma”. Our search TRANSCEND FL, lisocabtagene maraleucel showed deep and of Laboratory Medicine and identified two manuscripts reporting clinical study results of durable responses with high survival rates at 24 months in Medicine at Huddinge, Center of Allogeneic Stem Cell chimeric antigen receptor (CAR) T-cell therapy in marginal zone patients with relapsed or refractory MZL. The clinical benefit of Transplantation and Cellular lymphoma (MZL). Both manuscripts were based on ZUMA-5, lisocabtagene maraleucel was observed in a broad population Therapy, Karolinska Institutet a single-arm, multicentre, phase 2 study of axicabtagene of patients, showing high response rates across all subgroups. and University Hospital, ciloleucel in patients with relapsed or refractory indolent non- The safety profile was manageable, and no new safety signals Karolinska Comprehensive Cancer Center, Karolinska Hodgkin lymphoma, representing results from the primary were identified beyond those observed in lisocabtagene ATMP Center, H5 Laboratories analysis and the 3-year follow-up. Although axicabtagene maraleucel studies in other B-cell malignancies. These data Medicine, Stockholm, Sweden ciloleucel showed high response rates and durable responses in support a one-time infusion of lisocabtagene maraleucel as an (Prof S Mielke MD); Azienda Socio Sanitaria Territoriale patients with relapsed or refractory MZL, the number of effective treatment option for patients with relapsed or Papa Giovanni XXIII, Bergamo, patients with relapsed or refractory MZL was low (n=31 at refractory MZL after at least two previous lines of systemic Italy (A M Barbui MD); Hospital 3-year follow-up) and only included patients with nodal or therapy, a population with poor outcomes for which effective Universitario Virgen del Rocío, extranodal MZL. Furthermore, axicabtagene ciloleucel was and tolerable treatments are needed. Instituto de Biomedicina de Sevilla, Universidad de Sevilla, associated with substantial toxicities; grade 3 or higher Implications of all the available evidence Seville, Spain (J L R Ortega MD); cytokine release syndrome in two (8%) patients, grade 3 or TRANSCEND FL represents the most recent and extensive effort Southwest Oncology, higher neurological events in nine (38%) patients, and grade 3 CommonSpirit Mercy, to explore CAR T-cell therapy in the largest cohort of patients or higher infections occurred in seven (29%) patients. Findings Durango, CO, USA with relapsed or refractory MZL to date, building on the initial (L J Nastoupil MD); MD from ZUMA-5 remain to be validated in larger studies. observations from ZUMA-5. These results show that the CAR Anderson Cancer Center, Added value of this study T-cell therapy lisocabtagene maraleucel can provide meaningful Houston, TX, USA (S Ahmed MD); Bristol Myers TRANSCEND FL is a multicentre, clinical study, which evaluated clinical benefit, driving advances in the treatment of relapsed or Squibb, Seattle, WA, USA CD19-directed CAR T-cell therapy in the largest number of refractory MZL. (A Avilion PhD); Bristol Myers Squibb, Boudry, Switzerland (M Bar MD, L Diaz MD, U Furustrand PhD, M Vedal PhD, deep and durable responses with a manageable safety received at least two previous lines of systemic therapy, S Colicino PhD); Bristol Myers profile in patients with relapsed or refractory large B-cell including at least one line of combination systemic Squibb, Princeton, NJ, USA (V Diab BSN, J Kumar MS, lymphoma, chronic lymphocytic leukaemia (CLL)–small therapy with an anti-CD20 antibody and an alkylating R Nishii PhD); Département lymphocytic lymphoma (SLL), mantle cell lymphoma, and agent, or had relapsed disease after haematopoietic d’Hématologie, Université de follicular lymphoma.11–16 TRANSCEND FL is a phase 2, stem cell transplantation. Full eligibility criteria are Lille, Centre Hospitalier pivotal study that aimed to assess the ecacy and safety of available in the appendix (pp 6–8, 90–95). Protocol Universitaire de Lille, Groupe de Recherche sur les formes lisocabtagene maraleucel in adults with relapsed or changes since study initiation are noted in the appendix Injectables et les Technologies refractory follicular lymphoma or MZL. Results in the (p 10). This study is registered with ClinicalTrials.gov, Associées, Lille, France follicular lymphoma cohorts were previously reported.13,17 NCT04245839. (Prof F Morschhauser MD) Here, we report the primary analysis for patients in the The study was done in accordance with the Declaration Correspondence to: relapsed or refractory MZL cohort. of Helsinki, International Conference on Harmonisation Dr M Lia Palomba, Memorial Sloan Kettering Cancer Center, Good Clinical Practice guidelines, and applicable New York, NY 10065, USA Methods regulatory requirements. Institutional review boards or palombam@mskcc.org Study design ethics committees at participating institutions approved See Online for appendix The MZL cohort of the global, phase 2, open-label, the study protocol and amendments (appendix p 5). All single-arm, multicohort TRANSCEND FL study patients provided written informed consent before any assessed the ecacy and safety of lisocabtagene study-related procedures. maraleucel in patients aged at least 18 years with diagnosis of MZL in 30 sites in the USA (14 sites), Procedures Canada (1 site), Europe (14 sites), and Japan (1 site). All patients underwent leukapheresis for lisocabtagene Patients must have had histologically confirmed MZL in maraleucel manufacturing. Bridging therapy for disease the 6 months before screening, as assessed by local control was allowed at the investigator’s discretion pathology; additionally, samples were sent for during manufacturing. If bridging therapy was retrospective central pathology assessment for all administered, reconfirmation of measurable disease enrolled patients. Patients must have had measurable per CT was required before receiving lymphodepleting disease per CT assessment. PET assessment was also chemotherapy (fludarabine 30 mg/m² and mandated at screening. Patients must have had relapsed cyclophosphamide 300 mg/m² intravenously daily for or refractory disease per investigator discretion and had 3 days). Patients received a single intravenous infusion 964 Articles of lisocabtagene maraleucel at a target dose of except cytokine release syndrome (CRS; graded per 100 × 10⁶ CAR+ T cells 2–7 days after lymphodepleting Lee and colleagues 2014 criteria21) and tumour lysis chemotherapy; retreatment with lisocabtagene syndrome (graded per Cairo–Bishop criteria22). Sex maraleucel was not allowed. Per protocol, patients with (biological attribute) was reported by clinicians. hypo gamma globulinaemia (serum IgG <500 mg/dL) should have been considered for intravenous IgG Statistical analysis therapy per institutional guidelines. Lisocabtagene Ecacy assessments were done in the lisocabtagene maraleucel infusion and monitoring in the outpatient maraleucel-treated ecacy analysis set, including all setting was allowed at the investigator’s discretion. patients who received lisocabtagene maraleucel and had Patients were to be followed up for up to 5 years in measurable disease as assessed by CT per IRC. The TRANSCEND FL. On completion or early 95% CIs for response rates were two-sided and based on discontinuation, all patients treated with lisocabtagene the exact Clopper–Pearson method. Time-to-event maraleucel are asked to enrol in a separate long-term endpoints were summarised with medians and 95% CIs follow-up study (NCT03435796) for up to 15 years after by use of the Kaplan–Meier method. Safety analyses lisocabtagene maraleucel infusion for assessments of were done in the lisocabtagene maraleucel-treated safety and survival. analysis set, including all patients who received lisocabtagene maraleucel. Patients who received non- Outcomes conforming product, defined as any product wherein The primary endpoint was overall response rate one of the CD8 or CD4 cell components did not meet per independent review committee (IRC) by CT based on one of the requirements to be considered lisocabtagene Lugano 2014 criteria (appendix pp 11, 144).18 Secondary maraleucel, but could be considered appropriate for ecacy endpoints were complete response rate, duration infusion, were not included in the lisocabtagene of response, duration of response in patients with a best maraleucel–treated analysis set or in the lisocabtagene overall response of complete response, progression-free maraleucel–treated ecacy analysis set. The cellular survival, and overall survival. Additional secondary kinetics set included patients in the lisocabtagene endpoints were safety measured as type, frequency, and maraleucel–treated analysis set who had at least severity of adverse events and laboratory abnormalities; one available measurement of cellular kinetics by PCR cellular kinetics measured by PCR; and patient-reported assessment. PROs were summarised descriptively and outcomes (PROs). The primary domains of interest in evaluated in the PRO analysis set, which included PRO assessments and corresponding thresholds are patients in the lisocabtagene maraleucel–treated reported in the appendix (pp 9, 12).19,20 Peripheral B-cell analysis set who completed a pre-lymphodepleting aplasia was assessed as an exploratory endpoint. chemotherapy baseline visit and at least one post- Additional prespecified analyses included DOR in baseline PRO measurement. Details on handling of patients with a best overall response of partial response missing data and intercurrent events are provided in the and prespecified ecacy subgroup analyses. Sensitivity appendix (p 9). analyses of primary and secondary ecacy endpoints, With a sample size of 60 patients with MZL treated with including ORR, complete response rate, duration of lisocabtagene maraleucel, by use of exact binomial one- response, progression-free survival, and overall survival, sample tests unadjusted for the hierarchical testing were done on the basis of the leukapheresed set procedure, there would be 90% power to test overall (intention-to-treat set). Post-hoc analyses included time to response rate and complete response rate endpoints next treatment and responses derived from investigator- versus null hypotheses (H) with one-sided 0·025 level assessed PET data in patients with PET-avid disease at testing. The H was up to 50% for overall response rate baseline. and up to 5% for complete response rate based on Disease assessment was done at screening and, for available clinical data at the time of study design.23 To patients who received bridging therapy, also before control the type I error rate, primary (overall response lymphodepleting chemotherapy. Response assessments rate) and secondary (complete response rate) endpoints were done at days 29 and 90; at months 6, 9, 12, 18, were tested hierarchically, with overall response rate and 24; and every 12 months thereafter until month 60 tested first at a one-sided 0·025 level. If the H for overall after infusion. Treatment-emergent adverse events were response rate was rejected, then complete response rate defined as adverse events that started any time from was subsequently tested at a one-sided 0·025 level lisocabtagene maraleucel infusion through and (appendix p 9). All statistical analyses were done with including 90 days after infusion. Neurological events SAS (version 9.4). were defined as investigator-identified neurological adverse events related to lisocabtagene maraleucel. Role of the funding source Adverse events, including neurological events, were The funder of the study led the study design, data graded per the National Cancer Institute Common collection, data analysis, data interpretation, and the Terminology Criteria for Adverse Events, version 5.0, writing of the report. Articles included rituximab (15 [22%] of 67), cyclophosphamide 77 leukapheresed intention-to-treat set (nine [13%] of 67), or prednisone (seven [10%] of 67), radiation therapy only (three [4%] of 67), and both systemic and radiation therapy (one [1%] of 67). Median 10 not infused with lisocabtagene maraleucel 4 died* (IQR) on-study follow-up in the lisocabtagene 3 no longer met eligibility criteria† maraleucel–treated analysis set was 24·1 months 2 received non-conforming product‡ 1 disease progression (18·1–30·0). In the lisocabtagene maraleucel–treated analysis set (table 1), median (IQR) age was 62 years (57–71). MZL 67 lisocabtagene maraleucel-treated subtypes included nodal (32 [48%] of 67), splenic analysis set (safety set) (18 [27%] of 67), and extranodal–mucosa-associated lymphoid tissue (17 [25%] of 67). 57 (85%) of 67 patients 1 efficacy not evaluable had Ann Arbor stage III–IV disease at screening, 1 CT imaging not repeated after bridging 53 (79%) of 67 had high-risk MZL-International therapy Prognostic Index (IPI), 24 (36%) of 67 had progression of disease before 24 months (POD24) from initiation of 66 lisocabtagene maraleucel-treated first-line immunochemotherapy, 26 (39%) of 67 had efficacy analysis set§ refractory disease to last systemic therapy, 41 (61%) of 67 had relapsed disease after last systemic therapy, and Figure 1: CONSORT diagram *Including three deaths due to disease progression and one to suicide; for these 15 (22%) of 67 had bulky disease on the basis of four patients, death was the reason for study discontinuation. †Including modified Groupe d’Etude des Lymphomes Folliculaires one patient who did not have marginal zone lymphoma histologically confirmed criteria. Median (IQR) previous lines of systemic within 6 months of screening, one patient with a substantial medical condition, therapy was 3 (2–4). Patient characteristics of the and one patient with worsening Eastern Cooperative Oncology Group performance status. ‡Non-conforming product was defined as any product leukapheresed set are reported in the appendix wherein one of the CD8 or CD4 cell components did not meet one of the (pp 14–15) and are consistent with the patient requirements to be considered lisocabtagene maraleucel, but could be characteristics of the lisocabtagene maraleucel–treated considered appropriate for infusion. §Patients who received lisocabtagene analysis set. maraleucel and had positive disease present before lisocabtagene maraleucel infusion per independent review committee. Patients without baseline In the 66 patients in the lisocabtagene maraleucel– assessment repeated after anticancer therapy for disease control and before treated ecacy analysis set, the primary endpoint of lisocabtagene maraleucel infusion were excluded. IRC-assessed overall response rate was met at 95% (63 of 66; 95% CI 87·3–99·1; p<0·0001), rejecting Results the H of up to 50% (figure 2A). The secondary endpoint The key results of this study are summarised in plain of complete response rate was met at 62% (41 of 66; language (appendix p 4). A total of 77 patients with 95% CI 49·3–73·8; p<0·0001), rejecting the H of up relapsed or refractory MZL were enrolled in the study to 5%. and underwent leukapheresis across the 30 sites The median duration of response was not reached (appendix p 3); patients were recruited between (NR) in the overall population and in patients with a best Nov 11, 2020, and Aug 24, 2023. Protocol deviations are overall response of partial response or complete noted in the appendix (p 13). Of the 77 leukapheresed response (figure 2; appendix p 16). The 24-month patients, 67 received lisocabtagene maraleucel and were (95% CI) duration of response rate was 89% (72·4–95·6) included in the lisocabtagene maraleucel–treated in the overall responder population, 89% (66·6–96·7) in analysis set; 66 were ecacy-evaluable (lisocabtagene patients with BOR of complete response, and 89% maraleucel–treated ecacy analysis set; figure 1). (62·2–97·2) in patients with best overall response of Reasons for not receiving lisocabtagene maraleucel were partial response (figure 2B). The complete response rate death (n=4; three due to disease progression and one due at 24 months for patients with best overall response of to suicide), no longer meeting eligibility criteria (n=3), complete response was 52% (95% CI 38·9–64·0) per disease progression (n=1), and receiving a non- IRC assessment. The median progression-free survival conforming product (n=2). 13 (19%) of 67 patients were and overall survival were NR (95% CI 34·8 months–NR) monitored in the outpatient setting. For leukapheresed and NR, respectively, with 24-month (95% CI) rates patients, the median (IQR) time from leukapheresis to of 86% (72·2–92·9) and 90% (79·8–95·6). The median lisocabtagene maraleucel availability was 29 days time to next treatment was NR; 24-month free of next (24–30), and the median (IQR) time from leukapheresis therapy rate was 87% (95% CI 75·9–93·4; appendix to lisocabtagene maraleucel infusion was 50 days p 31). Ecacy outcomes in the leukapheresed (intention- (43–56). 30 (45%) of 67 patients received bridging therapy to-treat) set, which included eight patients who did not during lisocabtagene maraleucel manufacturing. receive CAR T-cell therapy and two patients who received Bridging therapies included systemic therapy only non-conforming product, are reported in the appendix (26 [39%] of 67), most commonly with regimens that (p 17). 966 Articles Lisocabtagene Lisocabtagene maraleucel– maraleucel– treated analysis treated analysis set (n=67)* set (n=67)* Age, years 62 (57–71) (Continued from previous column) <65 years 37 (55%) Mucosa-Associated Lymphoid Tissue International Prognostic Index for ≥65 years 30 (45%) patients with extranodal–mucosa-associated lymphoid tissue MZL (n=17) ≥70 years 20 (30%) Low risk (0) 1 (6%) ≥75 years 10 (15%) Intermediate risk (1) 11 (65%) Sex High risk (2–3) 5 (29%) Male 39 (58%) Lactate dehydrogenase > upper limit of normal before 32 (48%) lymphodepleting chemotherapy Female 28 (42%) Bone marrow involvement at screening 28 (42%) Race ≥20% lymphoma cells in bone marrow 20 (30%) White 38 (57%) CNS involvement at screening 1 (1%) Asian 4 (6%) Splenomegaly at screening 21 (31%) Black or African American 1 (1%) Previous splenectomy 6 (9%) Not collected or unknown† 24 (36%) Previous lines of systemic therapy|| 3 (2–4) Ethnicity Previous haematopoietic stem cell transplantation 11 (16%); Hispanic or Latinx 1 (1%) all ASCT Not Hispanic or Latinx 45 (67%) Received previous rituximab and lenalidomide 15 (22%) Not reported 21 (31%) Received previous bendamustine 52 (78%) MZL subtype Received previous Bruton tyrosine kinase inhibitor 26 (39%) Nodal 32 (48%) Refractory to last systemic therapy** 26 (39%) Splenic 18 (27%) Relapsed after last systemic therapy** 41 (61%) Extranodal–mucosa-associated lymphoid tissue 17 (25%) Progression of disease ≤24 months from initiation of 24 (36%) Eastern Cooperative Oncology Group performance status at screening first-line chemoimmunotherapy 0 37 (55%) Received bridging therapy 30 (45%) 1 30 (45%) Time from initial MZL diagnosis to first progression, 2 (1–5) Ann Arbor stage at screening years Stage I 3 (4%) Time from initial MZL diagnosis to infusion, years 7 (4–10) Stage II 7 (10%) Data are n (%) or median IQR. mGELF=modified Groupe d’Etude des Lymphomes Stage III 8 (12%) Folliculaires. ASCT=autologous stem cell transplantation. MZL=marginal zone lymphoma. MZL-IPI=Marginal Zone Lymphoma International Prognostic Index. Stage IV 49 (73%) *Percentages may not add up to 100% due to rounding. †Due to some European mGELF criteria‡ 41 (61%) country regulations. ‡Met the following criteria at study screening: presence of Bulky disease at screening§ 15 (22%) B symptoms, cytopenias (leukocyte count <1 × 10/L or platelet count <100 × 10/L), bulky disease (single mass >7 cm or at least three masses >3 cm), or Follicular Lymphoma International Prognostic Index at screening splenomegaly.24 §On the basis of mGELF criteria, bulky disease was defined as any Low risk (0–1) 11 (16%) mass greater than 7 cm, or at least three masses (each >3 cm), per investigator’s Intermediate risk (2) 13 (19%) assessment. ¶For MZL-IPI, disseminated MZL was not assessed in this study and, therefore, patients were assigned a point for MZL subtype only if they had nodal High risk (3–5) 41 (61%) MZL; the proportion of patients with high-risk MZL-IPI might be under-reported Not available 2 (3%) in this study. ||Including chemotherapy, immunotherapy, and MZL-IPI¶ radioimmunotherapy. **Refractory disease was defined as a best response of stable disease or progressive disease after previous therapy. Relapsed disease was Low risk (0) 0 defined as relapse after initial complete response or partial response to previous Intermediate risk (1–2) 14 (21%) therapy. High risk (3–5) 53 (79%) Table 1: Demographics and baseline characteristics (lisocabtagene (Table 1 continues in next column) maraleucel–treated analysis set; n=67) Overall response rate, complete response rates, and with more recent (≤24 months) or earlier (>24 months) 24-month rates of duration of response and progression- bendamustine exposure before leukapheresis (appendix free survival among subgroups were consistent with pp 18, 36–37). those of the overall population, with all three MZL In the post-hoc analysis of PET-based response per subtypes and high-risk feature subgroups showing investigator’s assessment in 56 patients with PET-avid numerically similar responses (figure 3; appendix disease at baseline, lisocabtagene maraleucel showed an pp 32–35). Outcomes were consistent regardless of overall response rate of 98% (55 of 56) and a complete previous bendamustine exposure (figure 3; appendix response rate of 91% (51 of 56). Consistent with CT-based pp 18, 32–35) with no major dierences between patients assessment, median (95% CI) duration of response and Articles 100 Overall response rate 95% n=63 (95% CI* 87·3–99·1) p<0·0001† 90 Complete response rate 62% n=41 (95% CI* 49·3–73·8) p<0·0001† 70 62% 50 40 33% 30 n=41 n=22 2% 2% 2% 10 n=1 n=1 n=1 Complete Partial Stable Progressive NE response response disease disease Figure 2: Efficacy outcomes per independent review committee assessment by CT by use of Lugano 2014 criteria18 (efficacy analysis set; n=66) (A) Response rates. (B) Duration of response. (C) Progression-free survival. (D) Overall survival. NE=not evaluable. NR=not reached. *Two-sided 95% CI based on exact Clopper–Pearson method. †One-sided p value based on the exact binomial test (H of overall response rate ≤50%; H of complete response rate ≤5%). ‡Based on Kaplan–Meier estimates. §Based on the reverse Kaplan–Meier 0 0 method. progression-free survival per PET were NR was 23·0 months (22·3–23·4) for duration of response (33·9 months–NR) and NR (34·8 months–NR), and 24·0 months (23·4–24·5) for progression-free respectively, with 24-month rates (95% CI) of 84% survival. (66·3–92·5) and 87% (74·9–93·7), respectively. In this All 67 (100%) lisocabtagene maraleucel–treated patients post-hoc analysis, the complete response rate at had at least one TEAE of any grade and 59 (88%) had 24 months per PET by investigators was 80% TEAEs of grade 3 or higher (appendix p 19). The most (95% CI 67·6–89·8). The median (95% CI) follow-up common any-grade TEAEs were CRS (51 [76%] of 67), 968 rep esnopser llarevo tseB )%( eettimmoc weiver tnednepedni A Efficacy analysis set (n=66) C (95% CI) 90 70 50 30 10 Median follow-up§: 23·8 months (95% CI 19·4–24·1) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 Time from lisocabtagene maraleucel infusion (months) Number at risk (censored) Third-line or 66 63 61 61 59 51 45 37 23 12 10 10 3 0 later marginal (0) (0) (0) (0) (1) (8) (5) (8) (13) (9) (2) (0) (6) (3) zone lymphoma Complete response 41 41 40 40 38 33 30 27 16 9 7 7 2 0 (0) (0) (0) (0) (1) (5) (3) (3) (10) (6) (2) (0) (4) (2) Partial response 22 22 21 21 21 18 15 10 7 3 3 3 1 0 (0) (0) (0) (0) (0) (3) (2) (5) (3) (3) (0) (0) (2) (1) lavivrus eerf-noissergorP )%( eettimmoc weiver tnednepedni rep D Partial response NR (26·4 months–NR)‡ Complete response NR (34·8 months–NR)‡ Third-line or later marginal zone NR (34·8 months–NR)‡ lymphoma 90 70 24-month progression-free survival‡ 60 86% (95% CI 72·2–92·9) 24-month progression-free survival in complete response‡ 90% (95% CI 70·3–96·9) 40 24-month progression-free survival in partial response‡ 30 90% (95% CI 65·9–97·5) 10 Median follow-up§: 24·5 months (95% CI 23·7–29·5) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Time from lisocabtagene maraleucel infusion (months) Number at risk (censored) Third-line or 66 64 64 64 63 54 51 42 35 23 16 15 7 4 3 0 later marginal (0) (0) (0) (0) (0) (7) (2) (9) (7) (10) (7) (1) (7) (3) (1) (3) zone lymphoma Complete response 41 41 41 41 40 35 35 29 25 17 11 11 6 4 3 0 (0) (0) (0) (0) (0) (4) (0) (6) (4) (7) (6) (0) (4) (2) (1) (3) Partial response 22 22 22 22 22 19 16 13 10 6 5 4 1 0 (0) (0) (0) (0) (0) (3) (2) (3) (3) (3) (1) (1) (3) (1) )%( lavivrus llarevO B 90 70 50 30 10 0 3 6 9 12 15 18 21 24 27 30 33 36 Number at risk (censored) Complete response 63 62 60 60 51 44 34 31 12 9 8 7 0 and partial response (0) (1) (0) (0) (8) (6) (10) (3) (18) (1) (1) (1) (6) Complete response 41 40 39 39 34 31 26 24 10 8 7 7 0 (0) (1) (0) (0) (4) (3) (5) (2) (13) (1) (1) (0) (6) Partial response 22 22 21 21 17 13 8 7 2 1 1 0 (0) (0) (0) (0) (4) (3) (5) (1) (5) (0) (0) (1) (95% CI) Partial response NR (26·4 months–NR)‡ Complete response NR‡ Third-line or later marginal zone NR‡ lymphoma 24-month overall survival‡ 90% (95% CI 79·8–95·6) 24-month overall survival in complete response‡ 95% (95% CI 80·9–98·7) 24-month overall survival in partial response‡ 95% (95% CI 68·1–99·2) rep esnopser fo noitaruD )%( eettimmoc weiver tnednepedni (95% CI) Partial response 25·6 (25·6 months–NR)‡ Complete response NR (24·5 months–NR)‡ Complete response and partial response NR (25·6 months–NR)‡ 24-month duration of response‡ 89% (95% CI 72·4–95·6) 24-month duration of response in complete response‡ 89% (95% CI 66·6–96·7) 24-month duration of response in partial response‡ 89% (95% CI 62·2–97·2) Median follow-up§: 21·6 months (95% CI 17·3–22·8) Time from response (months) Articles Evaluable patients Progression-free survival rate n at 24 months (95% CI) Overall 66 8855··77 ((7722··22––9922··99)) Age, years <65 36 8833··22 ((6622··99––9933··00)) ≥65 and <75 20 9900··00 ((6655··66––9977··44)) ≥75 10 9900··00 ((4477··33––9988··55)) Sex (biological attribute) Male 38 8855··22 ((6622··00––9944··88)) Female 28 8855··77 ((6666··33––9944··44)) Race White 38 8877··33 ((6688··11––9955··33)) Non-White 5 110000 (100·0–100·0) Ethnicity Not Hispanic or Latinx 45 8877··00 ((7700··33––9944··66)) Marginal zone lymphoma subtype Extranodal–mucosa-associated lymphoid tissue lymphoma 17 8888··22 ((6600··66––9966··99)) Nodal 32 9900··44 ((7733··11––9966··88)) Splenic 17 7733··55 ((3322··66––9911··99)) Relapsed vs refractory Relapsed 41 8844··22 ((6633··22––9933··77)) Refractory 25 8877··66 ((6666··33––9955··88)) Bulky disease at screening† Yes 14 9922··99 ((5599··11––9999··00)) No 52 8833··44 ((6666··44––9922··33)) Progression of disease within 24 months from initial immunochemotherapy Yes 23 7733··44 ((3388··22––9900··55)) No 43 9900··77 ((7777··11––9966··44)) Number of previous systemic lines of therapies 2 29 7777··66 ((5500··33––9911··11)) 3 16 8877··55 ((5588··66––9966··77)) ≥4 21 9944··44 ((6666··66––9999··22)) Previous autologous stem cell transplantation Yes 11 8800··88 ((4422··44––9944··99)) No 55 8866··44 ((6699··99––9944··22)) Previous Bruton tyrosine kinase inhibitor at any time Yes 26 9900··00 ((4477··33––9988··55)) No 40 8822··11 ((6666··00––9911··11)) Previous lenalidomide plus rituximab Yes 15 8866··77 ((5566··44––9966··55)) No 51 8844··99 ((6677··00––9933··55)) Previous bendamustine Yes 51 8899··99 ((7777··33––9955··77)) No 15 6644··66 ((1177··66––8899··66)) Bridging therapy Yes 29 8855··22 ((5588··77––9955..33)) No 37 8866··44 ((7700··44––9944··11)) 0 10 20 30 40 50 60 70 80 90 100 Figure 3: Forest plots of subgroup analysis: 24-month rates of progression-free survival per independent review committee based on CT assessment (efficacy analysis set; n=66)* mGELF=modified Groupe d’Etude des Lymphomes Folliculaires. *95% CIs (represented as bars) were based on Kaplan–Meier estimates in the efficacy-evaluable population. Analyses were done in subgroups with at least five patients. †Based on mGELF criteria, bulky disease was defined as any mass greater than 7 cm, or at least three masses (each >3 cm) per investigator’s assessment. neutropenia (50 [75%] of 67), and thrombocytopenia on day 47 and one event of T-cell lymphoma on day 32). (26 [39%] of 67; table 2). The most common grade 3 or Lisocabtagene maraleucel transgene testing and higher TEAEs were neutropenia (48 [72%] of 67), integration site analysis suggested that the T-cell thrombocytopenia (14 [21%] of 67), and leukopenia lymphoma was not derived from CAR T cells. (13 [19%] of 67). Grade 5 TEAEs occurred in Any-grade CRS occurred in 51 (76%) of 67 patients with two (3%) of 67 patients (one event of neutropenic sepsis a median time to onset of 4 days (IQR 2–7) and median Articles p 24). Of patients with grade 3 or higher cytopenia at day 29 Any grade Grade ≥3 and laboratory results available after day 29, most had Any 67 (100%) 59 (88%) recovered to grade no more than 2 by day 90. Of patients Most common (≥10% in any grade) with grade ≥3 cytopenia at day 90 and laboratory results Cytokine release syndrome 51 (76%) 3 (4%) available after day 90, all recovered up to grade 2 by day 365 Neutropenia 50 (75%) 48 (72%) (table 3; appendix p 24). The proportion of patients with Thrombocytopenia 26 (39%) 14 (21%) hypogammaglobulinaemia (serum IgG <500 mg/dL) did Anaemia 21 (31%) 12 (18%) not change substantially over time, with an incidence of Diarrhoea 19 (28%) 1 (1%) 24 (41%) of 59 at baseline, 35 (57%) of 61 at month 1, and Hypokalaemia 16 (24%) 2 (3%) 21 (53%) of 40 at month 24 (appendix p 38). Fatigue 15 (22%) 1 (1%) Nine (13%) of 67 patients received concomitant intravenous Leukopenia 15 (22%) 13 (19%) IgG therapy. Grade 3 or higher infections were reported in Headache 14 (21%) 1 (1%) 11 (16%) of 67 patients (six [9%] of 67 patients during the Tremor 13 (19%) 0 treatment-emergent period and seven [10%] of 67 patients Nausea 12 (18%) 1 (1%) during the post-treatment-emergent period). Second Increased aspartate aminotransferase 9 (13%) 2 (3%) primary malignancies occurred in eight (12%) of 67 patients Dizziness 8 (12%) 0 (appendix pp 25–27; four patients had non-melanoma skin Hypophosphataemia 8 (12%) 3 (4%) cancer, two patients had acute myeloid leukaemia, Lymphopenia 8 (12%) 7 (10%) one patient had myelodysplastic syndrome, and one patient Increased alanine aminotransferase 7 (10%) 4 (6%) had T-cell lymphoma [mentioned above as grade 5 TEAE]); Decreased appetite 7 (10%) 2 (3%) further details are reported in the appendix (p 25). Pyrexia 7 (10%) 0 Macrophage activation syndrome–haemophagocytic Hypotension 7 (10%) 0 lympho histiocytosis occurred in three (4%) of 67 patients; all events were grade 3 and all resolved (appendix p 27). Data are n (%). TEAE=treatment-emergent adverse event. *TEAE was defined as One (1%) patient had grade 1 tumour lysis syndrome. any adverse event that occurred from initiation of lisocabtagene maraleucel infusion and up to 90 days after infusion. Any adverse event that occurred after Among 77 leukapheresed patients, 16 (21%) of 77 deaths the initiation of another anticancer treatment was not considered a TEAE. occurred on-study; six deaths occurred before infusion (among these six patients, four discontinued the study Table 2: Most common TEAEs* (≥10%; lisocabtagene maraleucel–treated analysis set; n=67) due to death [three due to disease progression and one due to suicide] and two discontinued before death [one due to disease progression and one due to worsening time to resolution of 4 days (IQR 3–8; table 3); all CRS Eastern Cooperative Oncology Group performance events resolved. 48 (72%) of 67 patients had grade 1 or 2 status]) and ten deaths occurred after CAR T-cell infusion CRS (grade 1 31 [46%] of 67; grade 2 17 [25%] of 67). (two each due to MZL or complication due to MZL, new Grade 3 CRS occurred in three (4%) of 67 patients and no malignancy or complication due to new malignancy, grade 4 or 5 CRS occurred. CRS was managed with pneumonia, and COVID-19, and one each due to tocilizumab alone in 20 (30%) of 67 patients, neutropenic sepsis and cardiac event; appendix p 28). corticosteroids alone in two (3%) of 67, and both Among the 13 patients monitored in the outpatient tocilizumab and corticosteroids in 17 (25%) of 67. setting, ten (77%) of 13 patients had CRS (all grade 1 Any-grade neurological events occurred in or 2), and six (46%) of 13 patients had neurological events 22 (33%) of 67 patients, with a median time to onset of (all grade 1 or 2). 11 (85%) of 13 patients were hospitalised 8·5 days (IQR 5–13) and median time to resolution of owing to adverse events. Median time from lisocabtagene 8 days (3–17); all neurological events resolved. maraleucel administration to first hospitalisation was 19 (28%) of 67 patients had grade 1 or 2 neurological 5 days (IQR 2–8) with a median duration of hospitalisation events (grade 1 ten [15%] of 67; grade 2, nine [13%] of 67). of 7 days (4–8). No patients were admitted to the intensive Grade 3 neurological events occurred in care unit. three (4%) of 67 patients and no grade 4 or 5 events In the cellular kinetic set, lisocabtagene maraleucel occurred (table 3). Neurological events were managed exhibited rapid expansion in 66 evaluable patients with with corticosteroids in 14 (21%) of 67 patients and with median (IQR) time to maximum expansion of 10 days anakinra in two (3%) of 67 patients. Among the 52 patients (10–13) after infusion (appendix p 29). Median (IQR) who had CRS or neurological events, onset of the first maximum expansion in 66 evaluable patients was event (CRS or neurological event) was within 15 days of 81 390 copies per µg (31 146–198 376) and median (IQR) lisocabtagene maraleucel infusion for all patients. area under the curve from 0 to 28 days in 59 evaluable Grade 3 or higher cytopenia at day 29 was reported in patients after infusion was 657 799 day*copies per µg 28 (42%) of 67 patients, including six (9%) of 67 with (213 897–1 579 477). Most patients (47 [71%] of 66 evaluable anaemia, 18 (27%) of 67 with neutropenia, and patients) had B-cell aplasia at baseline. B-cell aplasia 17 (25%) of 67 with thrombocytopenia (table 3; appendix incidence increased to 63 (100%) of 63 patients 15 days 970 Articles after lisocabtagene maraleucel infusion, then decreased Lisocabtagene steadily from month 2, with an incidence of 48 (83%) of 58 maraleucel–treated at month 6, 40 (67%) of 60 at month 12, 31 (61%) of 51 at analysis set (n=67) month 18, and 26 (68%) of 38 at month 24 (appendix p 39). CRS* Among patients with available PRO data, completion Any grade 51 (76%) rates for both EORTC QLQ-C30 and FACT-LymS Grade 1 31 (46%) assessments were greater than 83% up to 18 months Grade 2 17 (25%) (appendix p 38). For EORTC QLQ-C30 primary domains, Grade 3 3 (4%) the mean baseline scores among patients analysed in this Grade 4/5 0 study were generally similar to the EU general population Time to first onset of CRS, days 4 (2–7) mean scores, except for pain, which was lower. The mean Time to resolution of first CRS, days 4 (3–8) baseline scores were generally better than those of the US Treatment for CRS general population (appendix p 30). After an initial Tocilizumab only 20 (30%) transient deterioration between day 1 and day 15, the mean Corticosteroids only 2 (3%) scores on most EORTC QLQ-C30 primary domains of Both tocilizumab and corticosteroids 17 (25%) interest started to improve between day 15 and day 60 Tocilizumab or corticosteroids, or both 39 (58%) (global health status–quality of life, role functioning, and Neurological events† pain) and between day 15 and day 90 (physical functioning and fatigue) and were generally maintained throughout Any grade 22 (33%) subsequent visits (appendix p 38). The mean changes in Grade 1 10 (15%) these five domains exceeded the contemporary threshold Grade 2 9 (13%) for clinically meaningful improvement at some visits. Grade 3 3 (4%) Cognitive functioning remained stable, maintaining the Grade 4/5 0 high baseline score (appendix p 41). After a transient Time to first onset of neurological event, days 8·5 (5–13) worsening between day 1 and day 15, the mean scores on Time to resolution of first neurological event, days 8 (3–17) FACT-LymS also started to improve between day 15 and Treatment for neurological events day 60 and remained consistent thereafter (appendix p 42). Corticosteroids only 14 (21%) Tocilizumab alone or in combination with corticosteroids 0 Discussion Grade ≥3 cytopenia at day 29 visit‡ 28 (42%) In this primary analysis of the MZL cohort of Recovered to grade ≤2 by day 90§ 21/28 (75%) TRANSCEND FL, a single infusion of lisocabtagene Recovered to grade ≤2 by day 365§ 27/28 (96%) maraleucel showed deep, durable responses in patients Grade ≥3 cytopenia at day 90 visit‡ 16 (24%) with relapsed or refractory MZL after at least two previous Recovered to grade ≤2 by day 180§ 7/16 (44%) lines of systemic therapy. The study’s primary and Recovered to grade ≤2 by day 365§ 16/16 (100%) secondary ecacy endpoints were met. Second primary malignancy¶ 8 (12%) Lisocabtagene maraleucel showed durable responses Grade ≥3 infection|| 11 (16%) with high survival rates at 24 months; outcomes by best During the 90-day treatment-emergent period** 6 (9%) overall response showed high survival rates in both During the post-treatment-emergent period†† 7 (10%) patients who achieved complete response and those who Macrophage activation syndrome–haemophagocytic lymphohistiocytosis (all 3 (4%) achieved partial response per CT assessment. The clinical grade 3 and all resolved) benefit of lisocabtagene maraleucel was observed across a Tumour lysis syndrome 1 (1%) broad population, which included all three MZL subtypes. Infusion-related reaction 0 Although limited by the small number of patients in Data are n (%), n/N (%), or median (IQR). CRS=cytokine release syndrome. *Graded according to the Lee 2014 criteria.21 certain subgroups, subgroup analyses showed consistent †Defined as investigator-identified neurological adverse events related to lisocabtagene maraleucel and graded per the results with the overall population, including in subgroups National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. ‡Grade 3 or higher laboratory results based on local laboratory assessments of decreased haemoglobin, neutrophil, or platelet count at the day 29 by MZL subtype or high-risk features such as POD24, (±2 days) or day 90 (±14 days) visit. §Recovery data are presented for patients with grade 3 or higher cytopenia at refractory disease, or high tumour burden. Ecacy day 29 or day 90. ¶Including four patients with non-melanoma skin cancer, two patients with acute myeloid outcomes were similar and consistently high regardless of leukaemia, one patient with T-cell lymphoma, and one patient with myelodysplastic syndromes. ||Some patients timing of previous bendamustine exposure before might have grade 3 or higher infections in both treatment-emergent and post-treatment-emergent periods. **Five patients had grade 3 infections: pneumonia, COVID-19 infection, sepsis, sinusitis, and staphylococcal sepsis leukapheresis. (n=1 each); all grade 3 infections resolved. One patient had grade 5 neutropenic sepsis (mentioned in manuscript as The safety profile of lisocabtagene maraleucel was grade 5 treatment-emergent adverse event). ††Seven patients had nine events of grade 3 or higher infection: manageable with low rates of grade 3 CRS and COVID-19 (n=4; including pneumonia [n=1]) and other pneumonia (n=5). All events resolved. neurological events and no grade 4 or 5 CRS and Table 3: Adverse events of special interest (lisocabtagene maraleucel–treated analysis set; n=67) neurological events; no new safety signals emerged in the MZL population.11–15,25–28 Although any-grade CRS was commonly reported in the MZL patient population (76%); the frequency of these events was within the variations Articles observed with lisocabtagene maraleucel across indications FL), there was no upper age limit for enrolment and (44% in large B-cell lymphoma, 59% in follicular 30% of lisocabtagene maraleucel–treated patients were lymphoma, 61% in mantle cell lymphoma, and 85% in aged 70 years and older with an upper age range of CLL–SLL). The incidence of CRS observed in MZL could 81 years. Furthermore, the median (range) of previous be related to circulating disease, potentially in patients lines of therapy was 3 (2–12) in TRANSCEND FL, 2 (1–6) with splenic MZL, similar to CLL–SLL. It is important to in MAGNOLIA, 1 (1–12) in AUGMENT, and 2 (1–8) in note that rates of severe CRS were similar and consistently MAGNIFY, indicating that patients with MZL in the low across the dierent indications, including MZL with TRANSCEND FL study were more heavily pretreated three (4%) patients who had grade 3 CRS and no grade 4 than those in the other studies. Additionally, 39% patients or 5 events. CRS and neurological events were managed in TRANSCEND FL were previously exposed to BTKi by use of the protocol-specified and standard-of-care and 22% to R². ZUMA-5 was a single-arm, multicentre, guidelines, and all events resolved. The rates of grade 3 or phase 2 study that evaluated axicabtagene ciloleucel in higher infections (9% in the treatment-emergent period) patients with third-line or later relapsed or refractory and grade 3 or higher cytopenias at day 29 (42%; most follicular lymphoma or MZL (nodal or extranodal).10,38 In resolved by day 90) were similar to the incidences reported the 3-year follow-up of patients with relapsed or with lisocabtagene maraleucel in other B-cell refractory MZL in ZUMA-5 (n=31; median age for MZL, malignancies.11–16 Although 68% had B-cell aplasia at 64 years), the response assessment by investigator per 24 months and 53% of patients had hypo- PET–CT showed an overall response rate of 77% and CR gammaglobulinaemia at 24 months, the rate of grade 3 or rate of 65% after a median follow-up of 32 months,10 higher infections was low (10% during the post-treatment- whereas in the MZL cohort of TRANSCEND FL, the emergent period). The incidence of second primary overall response rate was 98% and complete response malignancies (12%) was consistent with that published in rate was 91% in a post-hoc analysis based on investigator- the general MZL population.29–32 assessed PET data. The 18-month rates of This study also assessed PROs, including measures of progression-free survival and overall survival with quality of life, disease-related symptoms, and functioning. axicabtagene ciloleucel in patients with MZL from PRO completion rates were high during the 18-month ZUMA-5 were 43% and 83% per IRC, respectively,10 and study visit. Following a transient decline immediately were 89% and 90% per IRC, respectively, with after treatment, PRO scores were either maintained or lisocabtagene maraleucel in this study. In the MZL showed improvement over time. Treatment with cohort of TRANSCEND FL, grade 3 CRS or neurological lisocabtagene maraleucel was associated with sustained events occurred in 4% of patients each, with no grade 4 or enhanced quality of life over the 18-month period. or 5 events, whereas among patients with MZL in These PRO findings oer valuable insight into patients’ ZUMA-5, grade 3 or higher CRS occurred in 8% of direct experience with one-time lisocabtagene maraleucel patients, and grade 3 or higher NEs in 38%.38 The treatment in relapsed or refractory MZL, mirroring the incidence of grade 3 or higher infection was 16% with study outcomes showing clinical ecacy and manageable lisocabtagene maraleucel (treatment-emergent period, safety. 9%; post-treatment-emergent period, 10%) versus 29% Although direct cross-trial comparisons of ecacy and with axicabtagene ciloleucel, further underscoring the safety are not feasible owing to variation in study design well established safety profile of lisocabtagene and patient population, it is important to note certain maraleucel with low rates of severe infections in the observations that underscore the high ecacy and low treatment emergent and post-treatment emergent toxicity profile of lisocabtagene maraleucel in this study. periods.38 The ecacy observed with lisocabtagene maraleucel in We acknowledge that this study has some limitations. patients with relapsed or refractory MZL is encouraging A single-arm, open-label design was used because of the and appears to be substantially improved over that lack of established standard of care for patients with shown by the currently approved therapies in this third-line or later relapsed or refractory MZL, the low setting. In the MAGNOLIA study, the overall response incidence of MZL, and the high unmet need for rate, complete response rate, and 2-year progression-free treatment in this setting. No prespecified criteria were survival rate with zanubrutinib were 68%, 26%, and 71%, defined for race or ethnicity enrolment, and the majority respectively.33,34 In the AUGMENT and MAGNIFY of patients for whom data are available were White. studies, the overall response rate, complete response Subgroup analysis had low statistical power owing to the rate, and median progression-free survival with R² were small number of patients in some subgroups. The H for 64%–65%, 29%–39%, and 20·2–41·2 months, overall response rate and complete response rate were respectively.35–37 Although median age (62 years) in based on data from therapies available at the time that TRANSCEND FL was somewhat younger than in studies the study was designed and initiated (July, 2020) before with other agents for relapsed or refractory MZL (median results with zanubrutinib or R² became available. age of 70 years in MAGNOLIA for MZL, 68 years in Nonetheless, as noted above, substantially higher overall AUGMENT for MZL, 66 years in MAGNIFY for MZL or response rate, complete response rate, and 972 Articles progression-free survival were observed in our study Bristol Myers Squibb, C4 Therapeutics, Caribou Biosciences, Cellectar compared with those reported for currently approved Biosciences, Century Therapeutics, EMD Serono, Epizyme, Foresight Diagnostics, Genmab, Incyte, Interius Biotherapeutics, Janssen, therapies in relapsed or refractory MZL. Additionally, Karyopharm Therapeutics, Kite, Kymera Therapeutics, Lilly, MorphoSys, there were high rates of ongoing responses (89%) and Mustang Bio, Novartis, Ono Pharmaceutical, Roche, SeaGen, EMD progression-free survival (86%) with lisocabtagene Serono, and Takeda; honoraria from AbbVie, AstraZeneca, Bristol Myers maraleucel at 24 months, whereas corresponding rates Squibb, Janssen, Kite, and Regeneron; and research funding via institution from Bristol Myers Squibb, Cellectis, Merck, Mustang Bio, Regeneron, and were 73% and 71% with zanubrutinib in the MAGNOLIA SeaGen. KA discloses support for travel and attending meetings from study (rates not reported in MAGNIFY and AUGMENT). Bristol Myers Squibb, Gilead, and Novartis. PB discloses institutional However, longer follow-up will be needed to further grants from Incyte, Merck Sharp & Dohme, Miltenyi Biotec, and Takeda evaluate response durability and survival outcomes in Oncology; consulting fees from Bristol Myers Squibb, Gilead, Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology; honoraria from this population with indolent lymphoma. The AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Incyte, TRANSCEND FL study provides up to 5 years of Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology; and follow-up after lisocabtagene maraleucel infusion and a support for travel and attending meetings from Bristol Myers Squibb, separate long-term follow-up ancillary study will oer up Gilead, Incyte, Miltenyi Biotec, Roche, and Takeda Oncology. BTH discloses consulting fees and research funding from Bristol Myers to 15 years of follow-up. Squibb. AMG-S discloses consulting fees from AbbVie, AstraZeneca, TRANSCEND FL explored the ecacy and safety of Bristol Myers Squibb, Genmab, Gilead–Kite, GlaxoSmithKline, CAR T-cell therapy in the largest cohort of patients with IDEOGEN, Incyte, Janssen, Lilly, Miltenyi Biotec, Regeneron, Roche, and relapsed or refractory MZL. The primary analysis results Sobi; honoraria from AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead–Kite, IDEOGEN, Incyte, Janssen, Kyowa Kirin, Lilly, of the MZL cohort from TRANSCEND FL show that a Roche, Sobi, and Takeda; support for travel and attending meetings from one-time infusion of lisocabtagene maraleucel is a highly AbbVie, Bristol Myers Squibb, Gilead–Kite, Lilly, and Roche; data safety eective treatment option for patients with relapsed or monitoring or advisory board participation for AstraZeneca, Bristol Myers refractory MZL, providing meaningful clinical benefit to Squibb, and Regeneron; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the GELTAMO a patient population with a high unmet need. Foundation. GM discloses no conflict of interest. APR discloses data safety Contributors monitoring board participation for National Heart, Lung and Blood MLP, APS, and FM contributed to study concept or design and data Institute, Rapa Therapeutics, and University of Pennsylvania Abramson acquisition. SJS, RK, JSA, KA, PB, BTH, AMG-S, APR, GC, IF, KI, MK, Cancer Center. GC discloses consulting fees for Bristol Myers Squibb, SM, AMB, JLRO, GM, and SA contributed to data acquisition. LJN Mabqi, Onward Therapeutics, and Roche; honoraria from AbbVie, contributed to study concept or design. MLP, APS, FM, MB, LD, UF, Janssen, Novartis, and Takeda; and support for travel and attending VD, and JK contributed to data interpretation. MV, AA, RN, and SC meetings from Janssen and Roche. IF discloses consulting fees from contributed to data analysis and data interpretation. MLP, MB, LD, UF, AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Incyte, Janssen, VD, MV, AA, JK, RN, SC, and FM directly accessed and verified the data. Gilead–Kite, Merck, Novartis, Roche, SeaGen, and Takeda; speakers All authors contributed to writing of the manuscript, approved the final bureaus from AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, version, and agree to be accountable for all aspects of the work. Incyte, Janssen, Gilead–Kite, Novartis, Roche, and SeaGen; and support for travel and attending meetings from AbbVie, AstraZeneca, BeiGene, Declaration of interests Gilead–Kite, Roche, and SeaGen. KI discloses consulting fees from MLP discloses consulting fees from Bristol Myers Squibb, Kite, Novartis, AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Carna Biosciences, and Synthekine; and data safety monitoring or advisory board participation Chugai, Eisai, Genmab, Kyowa Kirin, Merck Sharp & Dohme, Mitsubishi for Bristol Myers Squibb and BeiGene. SJS discloses honoraria from Tanabe Pharma Corporation, Otsuka, Nippon Shinyaku, Novartis, Ono Janssen and Novartis; consulting or advisory roles for AbbVie, Pharma, Symbio, Takeda, Yakult, and Zenyaku; honoraria from AbbVie, AstraZeneca, BeiGene, BioNTech, Bristol Myers Squibb, Caribou Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Biosciences, Fate Therapeutics, Genentech, Genmab, Gilead–Kite, Incyte, Genmab, Gilead, Janssen, Kyowa Kirin, Lilly, Meiji Seika Pharma, Novartis, Janssen, Legend Biotech, Loxo Oncology, MorphoSys, Mustang Biotech, Nihon Kayakueutical, Ono Pharma, Pfizer, SymBio, Takeda; and Novartis, Regeneron, Roche, and viTToria Biotherapeutics; research institutional research funding from AbbVie, AstraZeneca, Bayer, BeiGene, funding from AbbVie, Adaptive Biotechnologies, Bristol Myers Squibb, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Genmab, Gilead, Incyte, DTRM Biopharma, Genentech, Incyte, Merck, Novartis, Pharmacyclics, Janssen, Kyowa Kirin, LOXO Oncology, Merck Sharp & Dohme, Novartis, and Roche; steering committee membership for Caribou Biotech and Otsuka, Pfizer, Regeneron, and Yakult. MK discloses consulting fees from Novartis; and patents for Methods for Treating CLL (autologous AbbVie, AstraZeneca, Bristol Myers Squibb, BeiGene, and Genentech; and co-stimulated T cells). RK discloses consulting fees from AbbVie, BeiGene, data safety monitoring board participation from Bristol Myers Squibb and Bristol Myers Squibb, Genentech–Roche, Genmab, Gilead–Kite, Lilly Genentech. SM discloses support for the present manuscript from Bristol Oncology, and Miltenyi Biotec; payment or honoraria for lectures, Myers Squibb; institutional grants or contracts from Gilead–Kite; presentations, speakers bureaus, manuscript writing, or educational events honoraria from Bristol Myers Squibb, Janssen, and Novartis; data safety for AstraZeneca, BeiGene, Bristol Myers Squibb, and Incyte–MorphoSys; monitoring board participation from Immunicum–Mendus and Miltenyi data safety monitoring or advisory board participation for AvenCell Biotec; leadership or fiduciary role, paid or unpaid, for SWECARNET; and Therapeutics and Calithera Biosciences; and committee or advocacy group other financial or non-financial interests from Scientify Research. participation, paid or unpaid, for American Society of Hematology AMB discloses grants or contracts from Incyte, Pierre Fabre, and Roche. committee on quality and ASCO National Comprehensive Cancer Network JLRO discloses consulting fees from Johnson & Johnson and Kite; guideline committee for histiocytic disorders. APS discloses support for honoraria from Amgen, Bristol Myers Squibb, Johnson & Johnson, and the current manuscript from Bristol Myers Squibb; consulting fees from Kite; and support for travel and attending meetings from Johnson & AbbVie, Alexion, AstraZeneca, BeiGene, Bristol-Myers Squibb, Epizyme, Johnson. LJN discloses support for the present manuscript from Bristol Genentech, Genmab, Jazz Pharmaceuticals, Janssen, Kite, Lilly, Myers Squibb; honoraria from AstraZeneca, Daiichi Sankyo, Genentech, MorphoSys, Novartis, and SeaGen; honoraria from AbbVie, ADC Gilead–Kite, Incyte, Janssen, Merck, Novartis, Regeneron, and Takeda; and Therapeutics, AstraZeneca, Bristol Myers Squibb, Genentech, Genmab, research support from Daiichi Sankyo, Genentech, Gilead–Kite, Incyte, Janssen, Jazz Pharmaceuticals, Kite, Lilly, and SeaGen; and data safety Janssen, Novartis, and Takeda. SA discloses consulting fees from Gilead– monitoring or advisory board participation for Alexion Pharmaceuticals Kite and Myeloid Therapeutics; honoraria from ADC Therapeutics, and Bristol Myers Squibb. JSA discloses consulting fees from AbbVie, Genmab, and Gilead–Kite; and research funding from Chimagen ADC Therapeutics, Alimera Sciences, AstraZeneca, BeiGene, bluebird bio, Articles Biosciences, Caribou Sciences, Genmab–Seattle Genetics, Janssen 15 Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene Oncology, Merck, and Nektar Therapeutics. MB, LD, UF, VD, MV, AA, JK, maraleucel for patients with relapsed or refractory large B-cell RN, and SC disclose employment and stock ownership in Bristol Myers lymphomas (TRANSCEND NHL 001): a multicentre seamless Squibb. FM discloses consulting fees from AbbVie, Bristol Myers Squibb, design study. Lancet 2020; 396: 839–52. Gilead, Janssen, and Roche; honoraria from AstraZeneca, Chugai, and 16 Abramson JS, Solomon SR, Arnason J, et al. Lisocabtagene Takeda; and data safety monitoring or advisory board participation for maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood 2023; AstraZeneca, Miltenyi Biotec, ModeX Therapeutics, and Roche. 141: 1675–84. Data sharing 17 Nastoupil L, Dahiya S, Palomba ML, et al. Lisocabtagene maraleucel Bristol Myers Squibb policy on data sharing can be found at https:// (liso-cel) in patients (pts) with relapsed or refractory (R/R) follicular www.bms.com/researchers-and-partners/independent-research/data- lymphoma (FL): Transcend FL 2-year follow-up. Blood 2024; sharing-request-process.html. Bristol Myers Squibb will honour 144 (suppl 1): 4387–90. legitimate requests for our clinical trial data from qualified researchers. 18 Cheson BD, Fisher RI, Barrington SF, et al. 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