Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

Abstract

The increasing number of approved therapies for relapsed mantle cell lymphoma (MCL) provides patients effective treatment options, with increasing complexity in prioritization and sequencing of these therapies. Chemo-immunotherapy remains widely used as frontline MCL treatment with multiple targeted therapies available for relapsed disease. The Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule. Lenalidomide and bortezomib are likewise approved for relapsed MCL and are active as monotherapy or in combination with other agents. Venetoclax has been used off-label for the treatment of relapsed and refractory MCL, however data are lacking regarding the efficacy of this approach particularly following BTKi treatment. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have emerged as highly effective therapy for relapsed MCL, with the CAR-T treatment brexucabtagene autoleucel now approved for relapsed MCL. In this review the authors summarize evidence to date for currently approved MCL treatments for relapsed disease including sequencing of therapies, and discuss future directions including combination treatment strategies and new therapies under investigation.

Keywords: cellular therapies; early progression of disease; novel agents; relapsed or refractory mantle cell lymphoma.

Figure 1

Authors’ Approach to Management of Mantle Cell Lymphoma at First Relapse. BTKi—acalabrutinib, ibrutinib, or zanubrutinib, CR- complete response, PR- partial response, SD- stable disease, PD- progressive disease, *- in select patients who favor time limited therapy and achieved prolonged duration of remission to frontline chemo-immunotherapy, would also consider chemo-immunotherapy as alternative option.

Figure 2

Author’s Approach to Management of Relapsed/Refractory Mantle Cell Lymphoma Following BTK inhibitor Treatment. BTKi—acalabrutinib, ibrutinib, or zanubrutinib, CAR-T- chimeric antigen receptor T cell therapy, brexucabtagene autoleucel is the only approved CAR-T treatment for mantle cell lymphoma at time of publication, R-BAC- rituximab, bendamustine, and cytarabine, *- patients with progression on BTKi require bridging therapy while awaiting CAR-T with either continuation of BTKi in cases with slow tempo of progression or with alternative therapies such as chemo-immunotherapy or venetoclax.