Bosutinib (BOS) versus imatinib (IM) in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) in the BELA trial: 18-month follow-up.

Abstract

6509 Background: The phase 3 BELA study compared BOS (competitive dual Src/Abl kinase inhibitor) with IM in newly diagnosed CP CML. Methods: 502 pts with CP CML stratified by Sokal score and region were randomized to oral BOS 500 mg/d (n = 250) or IM 400 mg/d (n = 252). Study design and endpoints have been described (Gambacorti, ASH 2010). Efficacy analyses included all randomized pts (ITT); safety analyses included all treated pts. Results: Median treatment duration was 16.6 mo for BOS and 16.8 mo for IM; 69% and 78% of pts, respectively, were still receiving therapy. CCyR rates at 1 y were 70% (BOS) and 68% (IM); cumulative CCyR rates by 1 y were 79% (BOS) and 75% (IM). MMR rates at 1 y were higher for BOS vs IM (39% vs 26%; P = 0.002), as were cumulative MMR rates by 1 y (47% vs 32%; P <0.001). Time to CCyR and MMR were significantly shorter with BOS (P <0.001 for both). Transformation to accelerated/blast phase occurred in 4 (2%) pts on BOS and 10 (4%) pts on IM (P = 0.053). Common treatment-emergent adverse events (TEAEs; ≥20% of pts) observed with BOS and IM, respectively, were diarrhea (68%, 22%), vomiting (31%, 14%), nausea (31%, 35%), rash (21%, 16%) and muscle cramps (4%, 20%). Pleural effusions were seen in 3% of BOS pts (no IM pts). Grade ≥3 TEAEs (≥2% of pts) seen with BOS were diarrhea (10%), vomiting (3%), pneumonia (3%), and dyspnea (2%). Median cumulative duration of diarrhea was 33 d for BOS and 17 d for IM. Grade ≥3 lab abnormalities (≥10% of pts) with BOS and IM, respectively, were elevated alanine aminotransferase (23%, 3%), thrombocytopenia (14%, 14%), elevated aspartate aminotransferase (11%, 3%), neutropenia (9%, 21%) and hypophosphatemia (4%, 17%). 22% of BOS pts and 6% of IM pts discontinued due to AEs, none due to diarrhea. Deaths occurred in 4 (1.6%) BOS pts and 12 (4.8%) IM pts; overall, 81% died from disease progression. Conclusions: Efficacy and safety were consistent with previously reported results. BOS showed a significantly higher MMR rate at 1 y, significantly faster times to CCyR and MMR, and lower transformation rate vs IM. BOS had a distinct and acceptable toxicity profile and may offer a new therapeutic option in newly diagnosed Ph+ CP CML. Data for 18-mo follow-up will be presented.