Treatment with acalabrutinib (Calquence) elicited a complete or partial response in more than 50% of patients with relapsed or refractory marginal zone lymphoma (MZL), according to interim results of a phase 2 study presented by L. Elizabeth Budde, MD, PhD, Associate Professor, Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, at the 2022 American Society of Clinical Oncology Annual Meeting.
“MZL is a rare, indolent B-cell lymphoma that is considered incurable after recurrence. Similar to many B-cell malignancies, the pathway involved in the pathogenesis of MZL can be moderated through inhibition of Bruton tyrosine kinase (BTK). Acalabrutinib is a next-generation BTK inhibitor approved for other malignancies. It has previously demonstrated activity in MZL,” Dr Budde explained.
Study Details
In the open-label phase 2 trial, 42 patients with histologically confirmed relapsed or refractory MZL who had received ≥1 previous systemic therapies were administered acalabrutinib 100 mg orally twice daily until disease progression or unacceptable toxicity.
The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
The study population was 60.5% male, and the median age was 69 years (range, 42-84 years). MZL subtypes were extra nodal (43%), nodal (31%), and splenic (26%).
At data cutoff (October 15, 2021), median follow-up duration was 10.7 months (range, 0.4-42.8 months). Among 35 patients evaluable for response, the investigator-assessed ORR was 54%, with 6 (16%) complete responses and 14 (38%) partial responses. The ORRs according to subtype were extra nodal (65%), nodal (44%), and splenic (45%). Seventeen (46%) patients had stable disease.
Median time to first response was 3 months, and median DOR was 19.3 months. Median PFS was 27.4 months, with a 12-month rate of PFS of 66%. Median OS was not reached.
Treatment with acalabrutinib monotherapy was generally well-tolerated, and most adverse events (AEs) were grades 1 or 2. Sixteen (38%) patients had grade ≥3 AEs, most commonly anemia, dyspnea, neutrophil count decrease (3 each); and fatigue, thrombocytopenia, and neutropenia (2 each). AEs resulting in treatment discontinuation occurred in 2 patients (grade 3 hypotension and grade 1 myalgia).
Among AEs of clinical interest, hypertension was reported in 2 patients (both grade 2). There were no cases of atrial fibrillation/flutter or major hemorrhage. There were 4 deaths reported (3 due to disease progression and 1 due to an AE).
“These early results indicate that acalabrutinib is efficacious and well-tolerated in patients with relapsed or refractory MZL. The adverse event profile is consistent with the known safety profile of acalabrutinib in other hematologic malignancies,” stated Dr Budde.
