First-line acotinib/acabrutinib plus chemoimmunotherapy improves PFS in elderly patients with MCL

Adding acalabrutinib to bendamustine and rituximab (BR) can significantly improve progression-free survival (PFS) in older patients with previously untreated mantle cell lymphoma (MCL), according to submitted data from the phase 3 ECHO trial. With a median follow-up of 45 months, median PFS was 66.4 months for acotinib plus BR (ABR) compared with 49.6 months for placebo plus BR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P=0.0160). Adding acotinib to older patients with MCL reduced the risk of disease progression or death by 27%.

Multi-center, double-blindThe ECHO trial enrolled 598 patients aged 65 years or older with previously untreated MCL and randomly assigned them to the second-generation BTK inhibitor acotinib plus BR or placebo plus BR. Akitinib/placebo was administered until disease progression or unacceptable toxicity occurred. Patients received 6 cycles of BR, with those in partial response or better receiving an additional two years of rituximab maintenance therapy. After progression in the placebo group, crossover to acotinib or other BTK inhibitors was allowed.

The overall response rate (ORR) in the acotinib group was 91.0%, while that in the placebo group was 88.0%. The complete response (CR) rate was 66.6% in the acotinib group and 53.5% in the placebo group. These differences did not reach statistical significance. Ninety-nine patients assigned to the placebo group developed progressive disease, 69% of whom received subsequent BTK inhibitor therapy. Although patients switched to ABR after disease progression, overall survival (OS) data showed a positive trend in favor of ABR (HR, 0.86; 95% CI, 0.65-1.13; P=0.27), although this was not statistically significant.

ECHO provides the first evidence that the addition of a BTK inhibitor to first-line standard chemoimmunotherapy in older patients with MCL results in a positive trend in overall survival. The OS curve shows that concurrent treatment is superior to subsequent treatment. Treatment-emergent adverse events (AEs) were balanced between arms, with a slightly higher incidence of serious AEs in the acotinib arm (69% vs. 62%). Treatment-emergent AEs leading to discontinuation occurred in 42.8% of the acotinib group and 31.0% of the placebo group. Atrial fibrillation (6.1% vs. 4.4%) and infections (78.1% vs. 71.0%) were more frequent in the acotinib group.

The study also looked at adverse events related to and foundAny adverse events, grade 3 or worse adverse events, and serious adverse events were higher in the ABR group. Specifically, COVID-19-related deaths occurred in 9.4% of patients treated with ABR compared with 6.7% of patients treated with placebo. After censoring for COVID-19-related deaths, median PFS improved in both treatment groups, with median PFS not reached in the ABR group compared with 61.6 months in the placebo BR group (HR, 0.64; 95% CI, 0.48-0.84; P=0.017). A similar effect was observed in OS (HR, 0.78; 95% CI, 0.56-1.07; P=0.12).

In this context, emerging data highlight the difficulties of BR beforeCAR-T cell therapy as a salvage option. It's important to see that the incorporation of acotinib reduced patients' progression by approximately 10% within 6-9 months of starting treatment. But this trial did not result in significant improvements in OS.