‘Sandwich’ Therapy Approach Yields High ORR, CR in Patients with MCL

Acalabrutinib plus rituximab, followed by chemotherapy and autologous hematopoietic stem cell transplant, is a safe and effective approach for MCL, according to a study presented at the 65th ASH Annual Meeting & Exposition.

Eliza Hawkes, MD, of the Olivia-Newton John Cancer Research Institute of Austin Health in Melbourne, Australia, and colleagues reported data from the phase II WAMM trial that included 44 patients with treatment-naïve MCL who received acalabrutinib plus rituximab in a “sandwich” approach.

Patients received two cycles of oral acalabrutinib 100 mg twice daily and intravenous rituximab 375mg/m² every four weeks. Following this window, patients received rituximab, dexamethasone, cytarabine, and oxaliplatin chemotherapy (RDHAOx) for four cycles. Patients then received fixed-duration acalabrutinib plus rituximab maintenance to improve therapy response and minimize additional toxicity.

The complete response (CR) rate and overall response rate (ORR) were 57% and 93% after acalabrutinib plus rituximab, respectively, and 88% and 95% after RDHAOx. Measurable residual disease (MRD) negativity was achieved in 18% of patients after acalabrutinib plus rituximab, and 94% after RDHAOx. Following a median follow-up of 22 months, the two-year overall survival was 89%.

“An [acalabrutinib plus rituximab] window yields a high ORR, and compared to historical studies, improves post-chemotherapy induction CR rates and MRD negativity,” reported Dr. Hawkes and colleagues.

Most patients (81%) experienced grade ≥3 adverse events (AEs) during induction or maintenance phases, most commonly neutropenia, febrile neutropenia, thrombocytopenia, and diarrhea. Serious AEs included COVID-19, febrile neutropenia, and fever. Five deaths occurred: four in patients with progressive disease and one from COVID-19 pneumonitis during acalabrutinib plus rituximab maintenance).

According to the researchers, analysis of survival, quality of life, and biomarkers will be reported during a follow-up.

Reference

Hawkes E, Lee S, Churilov L, et al. A window study of acalabrutinib & rituximab, followed by chemotherapy & autograft (ASCT) in fit patients with treatment naïve mantle cell lymphoma (MCL): first report of the investigator-initiated Australasian leukaemia & lymphoma group NHL33 ‘Wamm’ trial. Abstract #735. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.