Peg-IFNα2b Plus Dasatinib Active, Well Tolerated in First-line CP-CML

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) 57^th 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.

“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.”

Reference

1. 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: 57^th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.