ORLANDO, Fla. — The first-line combination of dasatinib with pegylated-interferon alpha 2b conferred a high rate of deep molecular response among patients with chronic phase chronic myeloid leukemia, according to study results from the French Intergroup of CML presented at the ASH Annual Meeting and Exposition.
The combination of pegylated-interferon alpha 2b (Peg-IFNa2b) and other tyrosine kinase inhibitors — including imatinib (Gleevec, Novartis) — has shown activity in this setting, resulting in a high rate of molecular response.
Lydia Roy, MD, a hematologist at Centre d'Investigation Clinique de Poitiers in France, and colleagues from the French Intergroup of CML sought to evaluate the efficacy of Peg-IFNa2b combined with the second-generation TKI dasatinib (Sprycel; Bristol-Myers Squibb, Otsuka) as front-line therapy for chronic phase CML.
Researchers conducted this study because, “second-generation TKIs, such as dasatinib, induced a faster and deeper molecular response in comparison to imatinib,” and that it made sense to try it in combination with Peg-IFNa2b, Roy said.
The analysis included data from 79 patients with chronic phase CML. The median age of the cohort was 48 years (range, 20-65 years) and 54% were men. Patients received 100 mg daily dasatinib. After 3 months, patients also received Peg-IFNa2b — for a maximum of 21 months of combination therapy — once they achieved platelet levels higher than 100 x 109/L, neutrophil levels higher than 1.5 x 109/L, and lymphocyte levels less than 4 x 109/L.
The cumulative rate of molecular response 4.5-log — or BCR-ABL1/ABL1IS of 0.0032% or lower, indicating disease remission and potential to be treatment free — at 12 months served as the study’s primary endpoint. Secondary endpoints included efficacy and safety.
Eighteen patients (22.7%) were not eligible to receive Peg-IFNa2b because their neutrophil (n = 10), platelet (n = 5) and lymphocyte counts (n = 1) did not reach the prespecified levels; they did not achieve a complete hematologic response (n = 1) or due to noncompliance (n =1).
The other 61 patients (77%) started Peg-IFNa2b at 30 µg/week in association with dasatinib.
After 3 months, 85% of the patients had a BCR-ABL1/ABL1 ratio of less than 10%.
Among these patients, the rate of major molecular response was 16% after 3 months, 51% after 6 months and 70% after 9 and 12 months. Data from five patients were pending.
The rate of deep molecular response 4.5-log was 10% at 6 months, 20% at 9 months and 30% at 12 months.
The rate of major molecular response for the patients who did not receive Peg-IFNa2b was 27% at 6 months and 50% at 9 months (missing data from two patients). Data were pending for six patients at 12 months.
Hematologic adverse events that occurred after 3 months included neutropenia (grade 1-2, n = 17; grade 3-4, n = 11), thrombocytopenia (grade 1-2, n = 7) and anemia (grade 1-2, n = 7). Only three of the 117 extra-hematologic adverse events were grade 3 to grade 4, and the most frequent events were infections (16%), general symptoms (15%), skin lesions (10%), hepato-biliary abnormalities (7.7%), nervous system/headache (7.7%), musculoskeletal pain (7%), psychiatric (7%) and gastrointestinal disorders (6%).
Overall, eight serious adverse events occurred after initiating Peg-IFNa2b, including two cases of grade 4 neutropenia and one case each of dysthyroitidis, dyspnea, pleural effusion, lymphoid hyperplasia, hemorrhoids and rectal fistula.
“Overall, the toxicity profile combination was manageable,” Roy said. “Among eligible patients, 79% are still on dasatinib plus Peg-IFN at 12 months.”
The study findings indicated the combination was feasible, and although the results need to be confirmed in a randomized trial, they are still “promising results that could further increase the rate of treatment-free remission,” Roy concluded. – by Anthony SanFilippo
Roy L, et al. Abstract 134. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.
Disclosure: The pegylated-interferon used in this trial was provided by Merck. Roy reports travel expenses and accommodations and research funding from, as well as speakers bureaus roles with Bristol-Myers Squibb and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.