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Review
. 2024 Jul;19(4):495-510.
doi: 10.1007/s11523-024-01070-z. Epub 2024 Jun 19.

Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review

Nathan Hale Fowler  1 , Julio C Chavez  2 , Peter A Riedell  3
Affiliations
Review

Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review

Nathan Hale Fowler et al. Target Oncol. 2024 Jul.

Erratum in

Abstract

Patients with follicular lymphoma, an indolent form of non-Hodgkin lymphoma, typically experience multiple relapses over their disease course. Periods of remission become progressively shorter with worse clinical outcomes after each subsequent line of therapy. Currently, no clear standard of care/preferred treatment approach exists for patients with relapsed or refractory follicular lymphoma. As novel agents continue to emerge for treatment in the third-line setting, guidance is needed for selecting the most appropriate therapy for each patient. Several classes of targeted therapeutic agents, including monoclonal antibodies, phosphoinositide 3-kinase inhibitors, enhancer of zeste homolog 2 inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and bispecific antibodies, have been approved by regulatory authorities based on clinical benefit in patients with relapsed or refractory follicular lymphoma. Additionally, antibody-drug conjugates and other immunocellular therapies are being evaluated in this setting. Effective integration of CAR-T cell therapy into the treatment paradigm after two or more prior therapies requires appropriate patient selection based on transformation status following a rebiopsy; a risk evaluation based on age, fitness, and remission length; and eligibility for CAR-T cell therapy. Consideration of important logistical factors (e.g., proximity to the treatment center and caregiver support during key periods of CAR-T cell therapy) is also critical. Overall, an individualized treatment plan that considers patient-related factors (e.g., age, disease status, tumor burden, comorbidities) and prior treatment types is recommended for patients with relapsed or refractory follicular lymphoma. Future analyses of real-world data and a better understanding of mechanisms of relapse are needed to further refine patient selection and identify optimal sequencing of therapies in this setting.

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Conflict of interest statement

Nathan Hale Fowler reports receiving grants or contracts from Novartis and TG Therapeutics and participation on a data safety monitoring board or advisory board for Gilead, BMS, and Roche. Julio C. Chavez reports a consulting/advisory role for Kite Pharma/Gilead, Novartis, Bayer, Karyopharm Therapeutics, Verastem, Pfizer, MorphoSys, TeneoBio, Juno Therapeutics, and Celgene; speaker’s bureau participation with Kite Pharma/Gilead, Genentech, AstraZeneca, and BeiGene; and research funding to the institute from Merck. Peter A. Riedell reports consulting for Novartis, BeiGene, and Celgene/BMS; research funding from Kite Pharma/Gilead, Novartis, Celgene/BMS, Calibr, Xencor, Tessa Therapeutics, and MorphoSys; receiving honoraria from Novartis; speaker’s bureau participation with Kite Pharma/Gilead; and membership as a board of directors or advisory committee for Novartis, Takeda, Janssen, Celgene/BMS, Bayer, and Karyopharm Therapeutics.

Figures

Fig. 1
Fig. 1
Logistics of chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed or refractory follicular lymphoma (r/r FL). Key steps and considerations for patients undergoing CAR-T cell therapy for r/r FL. Caregiver support varies by treatment center. AEs adverse events, CRS cytokine release syndrome
Fig. 2
Fig. 2
Practical guidance for chimeric antigen receptor (CAR) T-cell therapy in patients with with relapsed or refractory follicular lymphoma (r/r FL). Recommended strategy for identifying patients with r/r FL who are appropriate for receiving CAR-T cell therapy. These recommendations are based on the results from clinical trials of CAR-T cell therapy in patients with r/r FL and the authors’ clinical experience treating patients with r/r FL. BsAb bispecific antibody, CD cluster of differentiation, DLBCL diffuse large-B-cell lymphoma, ISRT involved-site radiation therapy, mAbs monoclonal antibodies, POD24 progression of disease within 2 years of initial chemotherapy, SCT stem cell transplant
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