Current and emerging treatments for R/R MCL

The development of novel targeted therapies and immunotherapeutic approaches has improved outcomes for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). However, long-term prognosis in patients with R/R MCL refractory to Bruton’s kinase inhibitors (BTKi) remains poor.  

Silkenstedt and Dreyling published a review of current and emerging treatment options for R/R MCL in Blood. The review focused on the use of combined targeted treatment strategies such as BTKi and immunotherapeutic approaches such as chimeric antigen receptor T cells and bispecific antibodies.

Key learnings

A retrospective cohort study of R-BAC showed an ORR of 83% in patients failing BTKi treatment. Additionally, a UK-based study in patients with R/R MCL (n = 211) showed high response rates and improved survival with post-ibrutinib R-BAC. 

Pirtobrutinib showed an ORR of 49.3% in patients with R/R MCL (n = 152) previously treated with covalent BTKi in the phase I/II BRUIN trial. Pirtobrutinib has the potential to be an alternative option for patients with low-risk MCL.  

Brexu-cel and liso-cel have demonstrated durable remissions with ORRs of 91% and 83.1%, respectively. CAR T-cell therapies should be considered as first-line therapy in high-risk patients refractory to BTKi, and as second-line therapy in patients with TP53 mutations. 

The CR rates of glofitamab + obinutuzumab, epcoritamab, odronextamab, and mosunetuzumab in patients with MCL were 73%, 25%, 33%, and 23%, respectively, suggesting promising early efficacy of BsAbs.