ASH 2017: Acalabrutinib Demonstrates Activity in Relapsed or Refractory Mantle Cell Lymphoma
At the 59th American Society of Hematology (ASH) Annual Meeting & Exposition, Wang et al presented results from the open-label, single-arm phase II ACE-LY-004 clinical trial, which served as the basis for the recent U.S. Food and Drug Administration (FDA) accelerated approval of acalabrutinib (Calquence) (Abstract 155). The findings demonstrated the safety profile and efficacy of acalabrutinib in the management of previously treated mantle cell lymphoma (MCL).
Michael L. Wang, MD, Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and principal investigator of the ACE-LY-004 MCL clinical trial, said, “Most people living with mantle cell lymphoma will unfortunately relapse, and new treatment options are greatly needed. As shown by the consistent overall response rates observed in this trial across several prespecified subgroups, acalabrutinib is a welcome new treatment option for certain patients with this aggressive blood cancer.”
ACE-LY-004 Trial
Summary of key investigator-assessed efficacy results from ACE-LY-004 (at a median follow-up of 15.2 months):
- The overall response rate was 81% (95% confidence interval [CI] = 73%–87%).
- The complete response rate was 40% (95% CI = 31%–49%).
- The partial response rate was 41% (95% CI = 32%–50%).
- The stable disease rate was 9% (95% CI = 4%–14%).
- The progressive disease rate was 8% (95% CI = 4%–14%).
- The rate of non-evaluable patients was 2% (95% CI = 1%–7%).
The overall response rate was consistent across multiple subgroups including age, tumor burden, and number or type of prior treatments. The secondary endpoint of median duration of response had not yet been reached at a median follow-up of 15.2 months. The median time to response, an exploratory endpoint, was 1.9 months.
After 12 months of treatment, 72% (95% CI = 62%–80%) of patients were still responding to acalabrutinib treatment. The secondary endpoints of progression-free survival and overall survival had not yet been reached; at 12 months, the progression-free survival and overall survival rates were 67% (95% CI = 58%–75%) and 87% (95% CI = 79%–92%), respectively.
In this trial, the most common nonhematologic adverse reactions (reported in ≥ 20% of patients at a median follow-up of 15.2 months) were headache (38%), diarrhea (30%), fatigue (26%), and myalgia (21%), per investigator assessment. Grade 3 or 4 adverse reactions (≥ 5%) included anemia (12%), neutropenia (11%), and pneumonia (6%).
Acalabrutinib was granted accelerated approval by the FDA in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. This indication is approved based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
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