FDA Approves Dasatinib for Pediatric Ph+ Chronic Phase CML

Lia Gore, MD

The FDA has approved dasatinib (Sprycel) for the treatment of pediatric patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

The approval is based on results with dasatinib demonstrated in 97 pediatric patients with CP-CML enrolled across 2 studies, an open-label, nonrandomized, single-arm phase II trial (CA180-226; NCT00777036) and an open-label, nonrandomized, dose-ranging phase I trial (CA180-018; NCT00306202). Fifty-one patients (all from the single-arm trial) were newly diagnosed, and the remaining 46 (29 from the single-arm study and 17 from the dose-ranging trial) were intolerant or resistant to prior imatinib (Gleevec).

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff, and thus, the median duration of complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR) could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response (DOR) for the newly diagnosed patients was 2.5+ to 66.5+ months for CCyR, 1.4 to 66.5+ months for MCyR, 5.4+ to 72.5+ months for patients who achieved MMR by month 24, and 0.03+ to 72.5+ months for patients who achieved MMR at any time. The ‘+’ denotes a censored observation. Among the imatinib-intolerant cohort, the DOR ranges were 2.4 to 86.9+ months for CCyR, 2.4 to 86.9+ months for MCyR, and 2.6+ to 73.6+ months for MMR.

“Options for pediatric patients with chronic myeloid leukemia are limited, and it is challenging to conduct clinical trials investigating potential new treatments in this small patient population,” Lia Gore, MD, University of Colorado School of Medicine and Children’s Hospital Colorado, said in a statement. “Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase.”

The 3-, 6-, 12-, and 24-month CCyR rates among newly diagnosed patients were 43.1% (95% CI, 29.3-57.8), 66.7% (95% CI, 52.1-79.2), 96.1% (95% CI, 86.5-99.5), and 96.1% (95% CI, 86.5-99.5), respectively. In the previously treated group, the corresponding rates were 45.7% (95% CI, 30.9-61.0), 71.7% (95% CI, 56.5-84.0), 78.3% (95% CI, 63.6-89.1), and 82.6% (95% CI, 68.6-92.2), respectively.

The 3-, 6-, 12-, and 24-month MCyR rates among treatment-naive patients were 60.8% (95% CI, 46.1-74.2), 90.2% (95% CI, 78.6-96.7), 98.0% (95% CI, 89.6-100), and 98.0% (95% CI, 89.6-100), respectively. The corresponding rates in the imatinib-intolerant group were 60.9% (95% CI, 45.4-74.9), 82.6% (95% CI, 68.6-92.2), 89.1% (95% CI, 76.4-96.4), and 89.1% (95% CI, 76.4-96.4), respectively.

The 3-, 6-, 12-, and 24-month MMR rates among newly diagnosed patients were 7.8% (95% CI, 2.2-18.9), 31.4% (95% CI, 19.1-45.9), 56.9% (95% CI, 42.2-70.7), and 74.5% (95% CI, 60.4-85.7), respectively. The corresponding rates in the previously treated group were 15.2% (95% CI, 6.2-28.9), 26.1% (95% CI, 14.3-41.1), 39.1% (95% CI, 25.1-54.6), and 52.2% (95% CI, 36.9-67.1), respectively.

Across both patient groups, 14.4% experienced treatment-related serious adverse events. Adverse events occurring in 15% or more of patients included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremity, and abdominal pain.

“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,” Vickie Buenger, President, Coalition Against Childhood Cancer, said in a statement. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”