A Pilot Trial of Imatinib, Low-Dose Cytarabine (ara-C) and Idarubicin (Ida) in Patients (pts) with Chronic Myeloid Leukemia (CML) in Myeloid Blastic Phase (BP).

Although imatinib is the single most effective agent in CML BP, only approximately 30% to 50% of pts achieve a hematologic response, and it is complete (CHR) and durable in 5% or less. Regimens including high-dose ara-C and daunorubicin are associated with remission rates of 20% to 25% in CML BP, a median survival of 3 months, and significant morbidities. Imatinib is additive or synergistic in vitro with ida and ara-C, particularly in imatinib-resistant cell lines. We thus investigated the efficacy of the combination of imatinib 600 mg daily, ara-C 10 mg daily subcutaneous, and Ida 12 mg/m² IV every 14 days in pts with CML in myeloid BP. Nineteen pts were treated, including 6 who had BP as their first manifestation of CML. Seventeen pts had failed prior imatinib as a single agent and had received a median of 5 prior therapies (range, 1 to 9). Median age was 54 yrs (range, 27–81) and the median WBC was 28.6 x 10⁹/L (range, 3.7 to 240.5), peripheral blood blasts 18% (range, 0 to 82), and bone marrow blasts 36% (range, 2 to 84). Four pts had extramedullary disease. Pts were treated for a median of 10.5 weeks (range, 4 to 124), receiving a median of 2 cycles (range 1 to 28). Fourteen (74%) pts responded, including 9 (47%) who achieved CHR, and 5 (26%) who returned to chronic phase. Four of the pts who achieved CHR also had a cytogenetic response (CGR) (3 complete, 1 minor). Responses lasted for a median of 10 weeks (range, 2 to 89 weeks). Two of 5 pts who failed to respond had a transient hematological improvement (>50% reduction of blasts in peripheral blood). Six pts were able to receive allogeneic BMT (4 in CHR, 1 in CP and 1 still in BP). Treatment was well tolerated and administered on an outpatient basis. Grade 3–4 non-hematological toxicities consisted of fatigue (n=4), vomiting (n=1), bone pain (n=1) and hyperbilirubinemia (n=1). Sixteen (84%) pts required brief hospitalization for neutropenic fever (n=8), bleeding (n=7), pneumonia (n=6), cellulitis (n=2) and CNS disease (n=2). Thirteen pts died: 4 after BMT and 9 due to disease progression. Among these, 4 had achieved CHR and 2 complete CGR. The median survival was 23 wks and 1 year survival rate 26%. In conclusion, the combination with imatinib + low-dose ara-C + Ida is an outpatient, well tolerated regimen that can induce responses in patients with CML BP who have failed imatinib and can be considered as an option to improve patient’s condition, and as a bridge to allogeneic BMT.