Bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy for indolent lymphoma


  • Isabelle Fleury, MD University of Montreal, Maisonneuve-Rosemont Hospital
  • Eva Laverdure, MD University of Montreal, Maisonneuve-Rosemont Hospital



Classic follicular (FL) and marginal zone (MZL) lymphomas are the primary indolent non-Hodgkin lymphomas (iNHL). Once first-line therapy is initiated, the majority of patients eventually experience treatment failure and face progressively shorter disease-free periods following subsequent lines of conventional chemotherapy. Patients with progressive disease within 24 months of first-line therapy (POD24) represent a significant unmet need. The five-year overall survival (OS) for patients with FL and POD24 is only 50% vs 90% for those without POD24. The three-year OS for patients with MZL is 53% and 95% respectively.

Author Biographies

Isabelle Fleury, MD, University of Montreal, Maisonneuve-Rosemont Hospital

Dre Isabelle Fleury is a hematologist and a medical oncologist working at Maisonneuve‑Rosemont Hospital in Montreal. She is a Clinical Associate Professor at the University of Montreal and is the Program Director of the fellowship in lymphoma and immune effector cells at University of Montreal. Her main interest is improving the care of patients with lymphoma. She is the Medical Lead of the lymphoma clinic at Maisonneuve Rosemont Hospital. She contributes to clinical research in lymphoma through participating in phase 1 to 3 trials. She is the instigator of the C3i Lymphoma Registry collecting clinical and bio clinical data to better understand lymphoma in the real-world setting. She participates in clinical trials of immune effector cells, is actively involved in the implementation of CAR-T in clinical practice in Quebec and is the medical lead of the Quebec immunocellular therapy network.

Eva Laverdure, MD, University of Montreal, Maisonneuve-Rosemont Hospital

Dre Eva Laverdure is a hematologist from the University of Sherbrooke with an interest in lymphoma and CAR-T cell therapy. She is currently consolidating her expertise through a fellowship in lymphoma and immune effector cells at Maisonneuve-Rosemont Hospital with the University of Montreal. 


Link BK, Day BM, Zhou X, et al. Second-line and subsequent therapy and outcomes for follicular lymphoma in the United States: data from the observational National LymphoCare Study. Br J Haematol. 2019;184(4):660-663. doi:

Casulo C, Byrtek M, Dawson KL, et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516-2522. doi:

Luminari S, Merli M, Rattotti S, et al. Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study. Blood. 2019;134(10):798-801. doi:

Sterner RC, Sterner RM. CAR-T Cell therapy: Current Limitations and Potential Strategies. Blood Cancer Journal. 2021;11(4):1-11. doi:

Amini L, Silbert SK, Maude SL, et al. Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nature Reviews Clinical Oncology. 2022;19(5):342-355. doi:

Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nature Reviews Immunology. 2021;22(2). doi: .

Hines MR, Knight TE, et al.. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Transplant Cell Ther. 2023 Jul;29(7):438.e1-438.e16.

Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. The Lancet Oncology. 2022;23(1):91-103. doi:

Chavez J, Sehgal AR, et al. 3-year follow-up analysis of ZUMA-5: a phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Blood (2022) 140 (Supplement 1): 10380–10383.

Fowler NH, Dickinson M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med 2022 Feb;28(2):325-332.

Dreyling M, Dickinson M, Martinez Lopez J, et al. Long-Term Clinical Outcomes and Correlative Efficacy Analyses in Patients (Pts) with Relapsed/Refractory Follicular Lymphoma (r/r FL) Treated with Tisagenlecleucel in the Elara Trial. Blood. 2022;140(Supplement 1):1459-1463. doi:

Morschhauser F, Dahiya S, et al. TRANSCEND FL: Phase 2 study results of lisocabtagene maraleucel (LISO-CEL) in patients (PTS) with relapsed/refractory (R/R) follicular lymphoma (FL). Hematol Oncol. 2023;41(S2):877-880.

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. The Lancet Oncology. 2022;23(8):1055-1065. doi:

Bartlett NL, Sehn LH, Matasar MJ, et al. Mosunetuzumab monotherapy demonstrates durable efficacy with a manageable safety profile in patients with relapsed/refractory follicular lymphoma who received ≥2 prior therapies: updated results from a pivotal phase II study. Blood. 2022;140(Supplement 1):1467-1470. doi:

Dean EA, Mhaskar RS, Lu H, et al. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Advances. 2020;4(14):3268-3276. doi:

Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. The Lancet Haematology. 2022;9(5):e327-e339. doi:

Novelli S, S. Luminari, M. Taszner, et al. Odronextamab in patients with relapsed/refractory follicular lymphoma (FL) Grade 1-3A: results from a prespecified analysis of the pivotal phase II study ELM-02. Hematol Oncol. 2023 June 9;41(S2):121-122.

Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. The Lancet. 2021;398(10306):1157-1169. doi:

Merryman R, Belada D, Sureda A, et al. 2023 ASCO Annual Meeting; Abstract. J Clin Oncol;41(16 suppl):750.

Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell–engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39(18):1959-1970. doi:

Ghione P, Palomba ML, Patel AR, et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022;140(8):851-860. doi:

Salles G, Schuster SJ, Dreyling M, et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Advances. 2022;6(22):5835-5843. doi:

Kymriah. [cited 2023 Oct 12]. Available from:

Yescarta. [cited 2023 Oct 12]. Available from:

Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231. doi:

Wang M, Munoz J, Goy A, et al. Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. J Clin Oncol. 2022;41(3). doi:



How to Cite

Fleury I, Laverdure E. Bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy for indolent lymphoma. Can Hematol Today [Internet]. 2023 Nov. 6 [cited 2024 Jun. 19];2(3):5-11. Available from: