Low-dose Dasatinib May Be Effective as Frontline Therapy in Chronic-phase Chronic Myeloid Leukemia
Dasatinib 100 mg is currently approved for chronic myeloid leukemia but has been associated with high rates of adverse events.
Low-dose dasatinib is active and well tolerated among patients with chronic-phase chronic myeloid leukemia (CML-CP), and may have clinical utility in the first-line setting, according to a study published in Cancer.1
As the efficacy of anticancer medicine — and therefore survival — improves, one of the biggest goals in oncologic care is to maintain efficacy while minimizing adverse events (AE). Dasatinib, a highly potent second-generation tyrosine kinase inhibitor, is currently approved for CML-CP at 100 mg once daily but has been associated with high rates of AEs (eg, pleural effusion, myelosuppression). A reduction in dose may lead to even further improved outcomes.
For this single-arm study, researchers assigned 75 patients with newly diagnosed Philadelphia chromosome (Ph)-positive CML-CP to receive dasatinib 50 mg once daily. Treatment was interrupted for grade 3 to 4 non-hematologic AEs and grade 4 neutropenia/thrombocytopenia, and was resumed upon adequate resolution. Routine blood counts with differential and blood chemistry were performed every 1 or 2 weeks in the first month and then every 4 to 8 weeks thereafter.
After a median follow-up of 9 months, 60 patients were evaluable for a response at 3 months.
Of study participants, 93% and 72% of patients reached BCR-ABL1 transcript levels of 10% or less and 1% or less, respectively, at 3 months, and the complete cytogenic response rate was 86% at 6 months and 88% at 12 months.
After 1 year, major molecular response, molecular response with a 4.0-log reduction, and molecular response with 4.5-log reduction was reached by 79%, 71%, and 46% of patients, respectively.
Dasatinib 50 mg had a good tolerability profile. Nine (12%) of patients had dose interruptions after 14 days or less during the first 3 months of treatment due to AEs, but resumed treatment upon resolution to grade 1 or lower; only 1 patient resumed treatment with dose-reduction.
Reduced-dose dasatinib was safe and effective in the frontline setting, achieving high rates of response and even cost savings. The authors concluded that “A confirmation of these findings is warranted. A randomized study comparing 50 mg of dasatinib with the standard dose could be considered.”
- Naqvi K, Jabbour E, Skinner J, et al. Early results of lower dose dasatinib (50 mg daily) as frontline therapy for newly diagnosed chronic-phase chronic myeloid leukemia [published online May 3, 2018]. Cancer. doi: 10.1002/cncr.31357