ORLANDO –Pegylated-interferon alpha 2b (Peg-IFNα2b) in combination with dasatinib as first-line therapy for patients with chronic myelogenous leukemia (CML) in chronic phase induces a high rate of deep molecular response during the first year of therapy with a manageable toxicity profile, a study presented at the American Society of Hematology (ASH) 57th Annual Meeting has shown.1
Because Peg-IFNα2a plus imatinib has demonstrated significantly higher rates of molecular responses compared with imatinib alone as first-line therapy for patients with CML in chronic phase, researchers sought to evaluate the efficacy and safety of dasatinib, a second-generation tyrosine kinase inhibitor, combined with Peg-IFNα2b as frontline therapy for chronic phase CML.
“A phase 2 trial using nilotinib and Peg-IFNα2a has reported high rates of deep molecular response,” said Lydia Roy, MD, of Hôpital Henri Mondor in Créteil, France, during her presentation. “Dasatinib, as a dual SCR/ALB kinase, may have distinct effects in combination with Peg-IFN.”
For the phase 2 trial, researchers enrolled 81 newly diagnosed patients less than 65 years of age with Philadelphia chromosome (Ph)-positive CML in chronic phase who started dasatinib 100 mg/day. At 3 months, patients were assigned to receive Peg-IFNα2b with dasatinib when platelets were greater than 100 x 109/L, neutrophils were greater than 1.5 x 109/L, and lymphocytes were less than 4.0 x 109/L. If those parameters were not met, patients continued dasatinib alone.
Reasons for not receiving Peg-IFNα2b included insufficient neutrophil count, platelet count, or lymphocyte count, absence of complete hematologic response, or non-compliance.
Results showed that at 12 months, the observed rate of molecular response 4.5log was 31%, demonstrating a high proportion of deep molecular response.
In regard to safety, the most frequent adverse events were infections, general symptoms, skin lesions, hepato-biliary abnormalities, nervous system/headache, musculoskeletal pain, psychiatric disorders, and gastrointestinal disorders. Hematologic adverse events included neutropenia, thrombocytopenia, and anemia. Five patients experienced immune disorders.
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“Overall, the toxicity profile combination was manageable,” Dr Roy noted. “Among eligible patients, 79% are still on dasatinib plus Peg-IFN at 12 months.”
The findings demonstrate the “feasibility of dasatinib and Peg-IFNα2b combination,” Dr Roy concluded. These results will need to be confirmed in a randomized trial, but they are “promising results in an attempt to increase further rate of treatment-free remission.”
- Roy L, Chomel J-C, Guilhot J, et al. Combination of dasatinib and peg-interferon alpha 2b in chronic phase chronic myeloid leukemia (CP-CML) first line: Preliminary results of a phase II trial, from the French Intergroup of CML (Fi-LMC). Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.