Treatment Landscape for Newly Diagnosed and Relapsed/Refractory MCL

A review published in Therapeutic Advances in Hematology summarized the treatment landscape of newly diagnosed and relapsed and refractory mantle cell lymphoma (MCL) and explores existing data on chimeric antigen receptor T-cell (CAR-T) in MCL (2022; 13:20406207221080738). 

Newly Diagnosed MCL

Initial treatment of MCL varies based on patient age and comorbidities. Younger, fit patients receive induction with intensive chemotherapy containing high-dose cytarabine followed by consolidation with autologous stem cell transplant (autoSCT). 

Induction regimens include the Nordic regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (maxi-CHOP) alternating with high-dose cytarabine and rituximab, R-CHOP alternating with rituximab, dexamethasone, cytarabine and a platinum-derivative (R-DHAP), and rituximab and bendamustine either alternating or sequentially given with rituximab and high-dose cytarabine.

Older patients and those with poor functional status may receive less-intensive chemotherapy and maintenance therapy with rituximab. In this population, regimens like bendamustine plus rituximab or bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) are preferred. In addition, lenalidomide and rituximab can be considered in those not eligible for intensive induction.

Relapsed and Refractory MCL

Among patients with refractory relapsed MCL, targeted agents are commonly used, with Bruton’s tyrosine kinase (BTK) inhibitors becoming the favored choices for second-line therapy. There are 3 BTK inhibitors approved by the FDA for the treatment of relapsed/refractory MCL: ibrutinib, acalabrutinib, and zanubrutinib.

Effective therapy for patients who relapse after BTK inhibitor therapy is an unmet clinical need. Considerations include chemoimmunotherapy, venetoclax, and CAR-T therapy. There are 4 anti-CD19 CAR-T approved by the FDA for B-cell lymphomas, including brexucabtagene autoleucel for refractory and relapsed MCL.

“Despite multiple advancements, MCL remains an incurable disease. Future directions in the treatment of MCL are moving toward utilizing combinations of different targeted agents such as the concurrent inhibition of BTK, BCL2, and targeting of CD19,” concluded the authors.