Targeting CD47: many misses; hopeful for a hit
Lindsay Wilde, Margaret Kasner
Abstract
Third, given that effective options for R/R TP53-mutated MCL are limited, maximizing the duration of initial response is key to achieving improved outcomes.In this study, 3 of the 6 patients with disease progression have already died due to their disease.There are varying results of the efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in R/R TP53-mutated MCL, 9-11 and the comparative efficacy of bispecific antibodies in this specific subgroup of patients with MCL is unknown.Given that BOVen is a highly active regimen with the majority of patients experiencing a complete remission with high rates of undetectable MRD, future directions should explore how to extend the durability of remission.Consolidation with CAR T-cell therapy, or bispecific antibodies, either alone or in combination with other novel agents including antibody drug conjugates, could be an effective strategy.Such an approach of early escalation to anti-CD19 CAR T-cell therapy is under investigation in generally high-risk patients in the ongoing WINDOW-3 study (NCT05495464).In conclusion, the authors deserve congratulations for conducting the first dedicated clinical trial in this high-risk MCL population.We look forward to the future data with longer follow-up and additional patients treated.Results from the ongoing trial of acalabrutinib, venetoclax, and obinutuzumab in a cohort enriched for TP53mutated disease (NCT04855695) could provide additional support for this triplet approach to become a new SOC.