Relapsed Mantle Cell Lymphoma: Treatment Strategies After CAR T-Cell Therapy

By: Noah Levine
Posted: Tuesday, February 18, 2025

Disease progression after chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory mantle cell lymphoma (MCL) remains a significant clinical challenge. At the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, Zachary D. Epstein-Peterson, MD, of Memorial Sloan Kettering Cancer Center, and colleagues presented the results of a multicenter study on treatment patterns and survival outcomes after CAR T-cell therapy in this patient population.

“Our data, the largest reported cohort of patients with disease progression after CAR T-cell therapy with resistant MCL, confirm the poor prognosis in this patient population, with a median overall survival of 5.4 months,” the investigators wrote.

The study authors analyzed data from 306 patients across 9 institutions who received CD19-directed CAR T-cell therapy for resistant MCL. Of them, 104 patients (34%) experienced disease progression after CAR T-cell therapy.

Patients who developed disease progression were predominantly male (73%), with a median age of 67 years at CAR T-cell infusion. Most had previously received Bruton’s tyrosine kinase (BTK) inhibitors. High-risk tumor features were prevalent before immunotherapy, including TP53 mutations (69%), Ki67 index ≥ 50% (71%), and blastoid/pleomorphic morphology (46%).

The median time to disease progression was 6 months after infusion. At the time of disease progression, high-risk MCL features remained common. Additionally, CD19-negative disease was observed in 12% of cases.

Following disease progression, 15 patients received no antilymphoma therapy, 11 patients underwent excision or radiation therapy, and 78 patients received systemic therapy. Among those patients, bispecific antibodies yielded the highest overall response rate at 60%, followed by small-molecule combinations. The BTK inhibitor pirtobrutinib (overall response rate of 31%), chemoimmunotherapy (overall response rate of 25%), and venetoclax (overall response rate of 20%) were also used. The median progression-free survival was 2.3 months, and overall survival was 5.4 months, with a 1-year overall survival rate of 33%.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.

2024 ASH Annual Meeting & Exposition