Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor, approved for use in adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL), an aggressive B-cell malignancy. Treatment-related adverse events (AEs) can adversely affect patient adherence to treatment regimens.
Objective: To review safety data from the ACE-LY-004 clinical trial long-term follow-up and report strategies implemented at MD Anderson to manage AEs in patients treated with acalabrutinib.
Methods: In the open-label, single-arm, phase 2 study, patients with R/R MCL received oral acalabrutinib (100 mg twice daily). All 124 patients enrolled on the ACE-LY-004 trial who received at least 1 dose of acalabrutinib were included in the efficacy and safety analysis. Our review focused on the most frequent AEs and those that led to treatment discontinuation.
Results: Overall, the median follow-up was 26 months, with 40% of patients remaining on treatment and 61% in follow-up for survival analysis. The median duration of response was 26 months, and median progression-free survival was 20 months. Discontinuations due to an AE occurred in 10 patients (8%), with each AE occurring in 1 patient. Overall, the most common AEs (mainly grade 1-2) were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). No patients discontinued treatment due to the most common AEs. A total of 28 patients (23%) were enrolled at MD Anderson. At MD Anderson, strategies implemented to manage adherence and AEs included providing patients with pill and toxicity diaries to help correlate medication intake with any treatment-related symptoms or AEs that might occur. Through completion of a pill diary, we show that patients were adherent to the twice-daily dosing with acalabrutinib. Where doses were missed or modified, patients were re-educated about the importance of adherence. Nurses provided education and counseling to patients when they experienced AEs, reminding them of the frequently observed AEs and that those AEs typically resolve over time. Grade 1-2 AEs did not require dose reduction or treatment interruption; instead, these were managed with over-the-counter medication (for example, acetaminophen for headache and loperamide for diarrhea) or prescription medication (for example, ropinirole for myalgia), if needed. To manage diarrhea, patients were advised to stay hydrated and consume small, frequent meals. The importance of staying active and well-hydrated was stressed to alleviate myalgia and fatigue symptoms.
Conclusions: Treatment of patients with R/R MCL with acalabrutinib has demonstrated efficacy and a good safety profile, with few discontinuations due to AEs. Strategies implemented at MD Anderson allow us to track occurrences of nonadherence and provide the opportunity to advise and educate patients and to manage AEs more effectively.
Funding: The study was funded by AstraZeneca.
Parts of this abstract were presented at PPLC 2018 and ONS 2019.
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