San Diego, California—Long-term response to acalabrutinib remained consistent with high efficacy and manageable safety in patients with relapsed or refractory mantle cell lymphoma (MCL), according to results from a follow-up analysis presented at the 2018 ASH Annual Meeting.

Acalabrutinib was approved for use in the treatment of adults with relapsed MCL by the FDA in 2017 based on clinical trial data showing a high rate of durable responses and a favorable safety profile in this patient population. At ASH 2018, lead investigator Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, presented the long-term follow-up results of the study behind these data.

The trial by Dr Wang and colleagues included 124 patients aged ≥18 years with confirmed relapsed or refractory MCL. The patients had a median of 2 previous therapies and received oral acalabrutinib 100 mg twice daily until disease progression or unacceptable toxicity.

As of February 12, 2018, the median study duration was 26.3 months, with 40% of patients remaining on treatment.

The investigator-assessed overall response rate was 91%, with 43% of patients achieving complete response. The overall response rates were consistent independent of tumor bulk, refractory disease, and previous therapies. The median duration of response was 25.7 months, median progression-free survival (PFS) was 19.5 months, and median overall survival (OS) was not reached, with an estimated 24-month OS of 72%.

The most common adverse events were primarily grade 1/2 and included headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). Grade 3/4 adverse events included anemia (10%), neutropenia (10%), and pneumonia (6%).

Cardiac events, including acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, and coronary artery disease, were reported in 13 patients. Hypertension events occurred in 4 (3%) patients, 1 of which was grade 3.

The most common bleeding events were contusion (13%) and petechiae (9%). Grade 3/4 infections occurred in 15% of patients.

Treatment discontinuation was primarily due to progressive disease (44%) and adverse events (8%). There were 43 (35%) deaths, primarily because of progressive disease (23%) or adverse events (5%). Deaths caused by adverse events included bilateral pulmonary embolism, critical aortic stenosis, myelodysplastic syndrome, pneumonia, and non–small-cell lung cancer. No deaths were considered related to acalabrutinib.

“Response to acalabrutinib remained consistent during long-term (>24-month) follow-up, including high response rates, median PFS of 19.5 months, and a median OS that has not yet been reached, confirming efficacy in patients with relapsed/refractory MCL,” Dr Wang and colleagues concluded.

“The AE [adverse event] profile was largely similar to earlier reporting, with limited additional safety events observed with an additional year of follow-up,” they added.—Janelle Bradley

Wang M, Rule S, Zinzani PL, et al. Long-term follow-up of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 2876.