Gastrointestinal Events And Management Strategies For Patients With Acute Myeloid Leukemia (Aml) In First Remission Receiving Cc-486 In The Randomized, Placebo-Controlled, Phase Iii Quazar Aml-001 Maintenance Trial

Context In the phase III QUAZAR AML-001 Maintenance Trial, CC-486, an oral hypomethylating agent significantly prolonged overall and relapse-free survival vs. placebo among patients with AML in first remission after induction chemotherapy (IC). Gastrointestinal (GI) events were the most frequent adverse events (AEs) with CC-486. Objective Assess GI AE rates with CC-486 over time and associated management strategies. Methods Eligible patients were aged ≥55 years and had AML with intermediate- or poor-risk cytogenetics, and ECOG-PS scores ≤ 3. Patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after IC ± consolidation and were not transplant candidates. Within 4 months of CR/CRi, patients were randomized 1:1 to once-daily CC-486 300-mg or placebo on days 1-14 of repeated 28-day cycles. Safety was assessed in patients who received ≥1 dose, through 28 days after the last dose. Prophylaxis and treatment of GI AEs was allowed but not mandatory. Results 236 patients received CC-486 and were evaluated for safety. Median age was 68 years (range, 55-86). Rates of any-grade nausea, vomiting, and diarrhea were 65%, 60%, and 50%, respectively; few patients experienced grade 3 (3%, 3%, and 5%) or serious (0.4%, 0.8%, and 1.3%) events, and only 1 grade 4 event (diarrhea) was reported. Rates were highest during initial treatment and decreased thereafter: in cycles 1-2, 3-4, and 5-6, nausea was reported in 53%, 17%, and 15% of patients, respectively; vomiting in 49%, 15%, and 10%; and diarrhea in 29%, 16%, and 11%. 5-HT3-antagonists, metoclopramide, lactulose, and loperamide were the most common concomitant medications; use of these agents also decreased over time. GI events required CC-486 dose-reductions for 6% of patients, treatment interruptions for 13%, and discontinuation for 5%. Conclusions Most GI AEs with CC-486 were low-grade, and events decreased in frequency after initial cycles. Use of GI medications decreased concurrently, suggesting progressive GI tolerance to CC-486. Few patients discontinued CC-486 due to GI AEs, indicating these events were easily managed. Clinicians and patients should be aware of possible GI events during early CC-486 treatment; prophylaxis and symptomatic intervention may facilitate treatment adherence to promote better outcomes.