Phase II study of MRD-driven ALR or ALO in previously untreated MCL

Results from a phase II study (NCT03863184), evaluating acalabrutinib + lenalidomide in combination with either rituximab (ALR) or obinutuzumab (ALO) in 34 patients with previously untreated mantle cell lymphoma (MCL), were published in Blood Advances by Ruan et al. Patients with undetectable measurable residual disease (<10⁻⁶) (uMRD6) in the peripheral blood (PB) were eligible to discontinue acalabrutinib + lenalidomide after 24 cycles; all patients received a minimum of 36 cycles of anti‑CD20 antibody treatment. The primary endpoint of this study was the molecular complete response (CR) rate after 12 cycles of induction, defined by Lugano criteria and uMRD6. Key secondary endpoints included safety, response rates, and survival. 

Key data: In the ALR cohort (n = 24), the overall response rate (ORR) was 100% (90% confidence interval [CI], 88–100) and the CR rate was 83% (90% CI, 66–94). uMRD6 in the PB was demonstrated in 67% of patients after 12 cycles of induction. At a median follow-up of 53 months, the 4‑year overall survival (OS) and progression-free survival (PFS) rates in patients receiving ALR were 91% and 76%, respectively. In the ALO cohort (n = 10), both the ORR and CR rate were 90% (90% CI, 61–100). uMRD6 in the PB was demonstrated in 90% of patients after 12 cycles of induction. At a median follow-up of 25 months, the 2‑year OS and PFS rates were both 100%. During induction, Grade 3/4 hematologic toxicities included asymptomatic neutropenia (ALR, 33%; ALO, 40%), anemia (ALR, 4%; ALO, 0%), and thrombocytopenia (ALR, 4%; ALO, 30%). 

Key learning: ALR and ALO demonstrated high rates of durable molecular responses in patients with previously untreated MCL, warranting further evaluation in response-adapted treatment strategies.