FDA Updates Dasatinib Label for Chronic Myeloid Leukemia

Nick Mulcahy

June 26, 2013

The US Food and Drug Administration has approved a change to the product labeling of dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), which updates efficacy and safety information for 2 of the drug's indications.

The labeling has been updated to include 3-year efficacy and safety data for patients with newly diagnosed Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) that is in the chronic phase. That indication was granted as an accelerated approval in 2010, necessitating the label updates.

The new labeling also includes 5-year data for patients with chronic-phase Ph chromosome-positive CML who are resistant or intolerant to imatinib mesylate (Gleevec, Novartis), which was that drug's original indication in 2006.

"These longer-term data add to the growing body of research around the safety and efficacy of [dasatinib] in first-line chronic-phase Ph chromosome-positive CML patients and those who are resistant or intolerant to imatinib," said Neil Shah, MD, PhD, from the University of California, San Francisco, who is a trial investigator, in a press statement. "CML requires ongoing treatment and assessment of treatment milestones in order to manage the disease properly. Given the chronic nature of CML, these long-term data are particularly important for patient care."

3-Year Data

The 3-year data come from DASISION (Dasatinib vs Imatinib Study in Treatment-Naïve CML Patients), an open-label randomized phase 3 international trial. DASISION is ongoing and further data will be required to determine long-term outcome.

The efficacy measures in that trial are molecular response rates (major molecular response, or MMR) and confirmed cytogenetic response rates (CCyR) at 12 months.

In DASISION, the primary end point of confirmed CCyR at 12 months was achieved by 259 patients (77%) treated with dasatinib and 260 (66%) treated with imatinib (P = .007).

At 36-month follow-up, more patients in the dasatinib group than in the imatinib group had confirmed CCyR (83% vs 77%), and median time to confirmed CCyR was worse in the 214 dasatinib responders than in the 201 imatinib responders (3.1 vs 5.8 months).

By 12 months, dasatinib patients were more likely than imatinib patients to achieve MMR (52% vs 34%; P < .0001). By 36 months, MMR at any time was higher for dasatinib than imatinib (69% vs 56%). In addition, MMR rates were higher with dasatinib than with imatinib at any time for those with Hasford scores considered low risk (81% vs 64%), intermediate risk (64% vs 56%), and high risk (61% vs 42%).

Fewer patients in the dasatinib group than the imatinib group had transformed to accelerated or blast-phase CML by 36 months (3% vs 5%).

According to Bristol-Myers Squibb press materials, the most frequently reported serious adverse reactions in patients with newly diagnosed chronic-phase Ph chromosome-positive CML were pleural effusion (4%), hemorrhage (2%), congestive heart failure (1%), pulmonary hypertension (1%), and pyrexia (1%). The adverse reactions reported by at least 10% of patients included myelosuppression, fluid retention events (pleural effusion and superficial localized edema), diarrhea, headache, musculoskeletal pain, rash, and nausea.

5-Year Data

Information added to the dasatinib labeling for chronic-phase Ph chromosome-positive CML patients with resistance or intolerance to previous imatinib therapy includes results from CA180-034, an open-label phase 3 dose-optimization trial.

At 5 years, 64% of patients were known to be alive; survival data on another 14% were unknown. While on treatment, less than 5% of dasatinib patients had transformed to accelerated or blast-phase CML by 5 years. The primary end point — major cytogenetic response in imatinib-resistant or -intolerant patients — was achieved by 63% of such patients receiving dasatinib at 2 years.

According to Bristol-Myers Squibb press materials, the most frequently reported serious adverse reactions were pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and central nervous system hemorrhage (1%). The adverse reactions reported by at least 20% of patients included myelosuppression, fluid retention events (pleural effusion and superficial localized edema), headache, diarrhea, fatigue, dyspnea, and musculoskeletal pain.

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