Is There Still a Role for Transplant for Patients with Mantle Cell Lymphoma (MCL) in the Era of CAR-T Cell Therapy?

Opinion statement For years, upfront autologous hematopoietic cell transplant (auto-HCT) has been the standard of care for younger and physically fit mantle cell lymphoma (MCL) patients after chemoimmunotherapy (CIT) induction. Bruton's tyrosine kinase (BTK) inhibitors have proven to be excellent salvage therapies, but their durability remains a question, especially in high-risk (HR) MCL. Allogeneic HCT (allo-HCT) was the only option for long-term remission and possibly cure for MCL relapse after auto-HCT and sometime as upfront consolidation for a young patient with HR MCL (debatable). We have seen a paradigm shift since the FDA approval in July 2020 of the brexucabtagene autoleucel chimeric antigen receptor T (CAR-T) cell therapy for relapsed and refractory (R/R) MCL with an preliminary evidence suggesting CAR-T may overcome known biological risk factors in MCL. Given its safety profile and excellent efficacy, the role of CAR-T among other approved therapies and HCT may need to be better defined. Based on the current evidence, auto-HCT remains a standard frontline consolidation therapy. CAR-T therapy is a preferred option for patients with relapsed/refractory (R/R) MCL, particularly those who failed BTK inhibitors. In certain high-risk MCL patients (such as high ki 67, TP53 alterations, complex karyotype, blastoid morphology, early relapse after initial diagnosis), CAR-T cell therapy may be considered before BTK inhibitors (preferably on a clinical trial). The role of allo-HCT is unclear in the CAR-T era, but remains a viable option for eligible patients who have no access or who have failed CAR-T therapy. Our review discusses current standards and the shifting paradigms in the indications for HCT and the role of CAR-T cell therapy for MCL. Prospective studies tailored based on risk factors are needed to better define the optimal sequences of HCT and cellular therapy and other approved novel therapies.

Automated summary

Autologous hematopoietic cell transplant (auto-HCT) has been the standard care for younger and physically fit mantle cell lymphoma (MCL) patients after chemoimmunotherapy (CIT) induction. Bruton's tyrosine kinase (BTK) inhibitors have shown good outcomes as salvage therapies, but their long-term efficacy remains uncertain, especially in high-risk MCL cases. Allogeneic HCT (allo-HCT) has been the primary option for long-term remission and possible cure in MCL relapse and some upfront consolidation cases. The recent approval of chimeric antigen receptor T (CAR-T) cell therapy for relapsed and refractory (R/R) MCL has brought about a paradigm shift, with preliminary evidence suggesting that CAR-T therapy may overcome known biological risk factors in MCL. The role of CAR-T therapy among other approved therapies and HCT needs to be further defined. Based on current evidence, auto-HCT remains the standard frontline consolidation therapy, while CAR-T therapy is preferred for R/R MCL patients, especially those who failed BTK inhibitors. In certain high-risk MCL cases, CAR-T cell therapy may be considered prior to BTK inhibitors, preferably as part of a clinical trial. The role of allo-HCT in the CAR-T era remains unclear but remains a viable option for eligible patients who have no access or have failed CAR-T therapy.