FDA Grants Regular Approval of Dasatinib for Pediatric Philadelphia Chromosome–Positive CML in Chronic Phase

On November 9, the U.S. Food and Drug Administration (FDA) expanded the indication for dasatinib (Sprycel) tablets to include the treatment of children with Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP).This approval for dasatinib in pediatric patients was granted under priority review, and the indication received orphan drug designation from the FDA.

Two Clinical Studies

The safety and efficacy of dasatinib in pediatric patients was evaluated in two pediatric studies of 97 patients with chronic-phase CML: an open-label, nonrandomized, dose-ranging trial (NCT00306202) and an open-label, nonrandomized, single-arm trial (NCT00777036). Among the 97 patients in the two studies, 51 patients (exclusively from the single-arm trial) had newly diagnosed chronic-phase CML and 46 patients (17 from the dose-ranging trial and 29 from the single-arm trial) were resistant or intolerant to previous treatment with imatinib.

Of the 97 pediatric patients with chronic-phase CML, 91 were treated with dasatinib tablets at 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The efficacy endpoints included complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR). Efficacy results (with 95% confidence intervals [CI]) for the two pediatric studies are summarized in the table below.

Efficacy of Dasatinib in Pediatric Patients With Chronic-Phase CML Cumulative Response Over Time by Minimum Follow-up

 

 

3 Months

 

6 Months

 

12 Months

 

24 Months

CCyR (95% CI)

 

 

 

 

 

 

 

 

Newly diagnosed (n = 51)

 

43.1% (29.3%–57.8%)

 

66.7% (52.1%–79.2%)

 

96.1% (86.5%–99.5%)

 

96.1% (86.5%–99.5%)

Prior imatinib (n = 46)

 

45.7% (30.9%–61.0%)

 

71.7% (56.5%–84.0%)

 

78.3% (63.6%–89.1%)

 

82.6% (68.6%–92.2%)

MCyR (95% CI)

 

 

 

 

 

 

 

 

Newly diagnosed (n = 51)

 

60.8% (46.1%–74.2%)

 

90.2% (78.6%–96.7%)

 

98.0% (89.6%–100%)

 

98.0% (98.6%–100%)

Prior imatinib (n = 46)

 

60.9% (45.4%–74.9%)

 

82.6% (68.6%–92.2%)

 

89.1% (76.4%–96.4%)

 

89.1% (76.4%–96.4%)

MMR (95% CI)

 

 

 

 

 

 

 

 

Newly diagnosed (n = 51)

 

7.8% (2.2%–18.9%)

 

31.4% (19.1%–45.9%)

 

56.9% (42.2%–70.7%)

 

74.5% (60.4%–85.7%)

Prior imatinib (n = 46)

 

15.2% (6.3%–28.9%)

 

26.1% (14.3%–41.1%)

 

39.1% (25.1%–54.6%)

 

52.2% (36.9%–67.1%)

 

With a median follow-up of 4.5 years in newly diagnosed patients, the median durations of CCyR, MCyR, and MMR could not be estimated, as disease had not progressed in more than half of the responding patients at the time of data cutoff. The range of duration of response was 2.5+ to 66.5+ months for CCyR, 1.4 to 66.5+ months for MCyR, and 5.4+ to 72.5+ months for subjects who achieved MMR by month 24 (and 0.03+ to 72.5+ months for subjects who achieved MMR at any time), where ‘+’ indicates a censored observation.

With a median follow-up of 5.2 years in imatinib-resistant or -intolerant patients, the median durations of CCyR, MCyR, and MMR could not be estimated, as disease had not progressed in more than half the responding patients at the time of data cutoff. The range of duration of response was 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, where ‘+’ indicates a censored observation.

Adverse Events and Dosing

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated pediatric patients with Philadelphia chromosome–positive CML in chronic phase. The most common adverse reactions (≥ 15%) included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremities, and abdominal pain.

Dasatinib is associated with the following warnings and precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor-lysis syndrome, embryofetal toxicity, and effects on growth and development in pediatric patients.

The recommended starting dosage for dasatinib in pediatric patients with Philadelphia chromosome–positive CML in chronic phase is based on body weight. The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

Dasatinib tablets should not be crushed, cut, or chewed. Tablets should be swallowed whole. The exposure in patients receiving a crushed tablet is lower than in those swallowing an intact tablet.

About Sprycel Assist

Bristol-Myers Squibb provides Sprycel Assist, which offers a single point of contact and live support and assistance for patients prescribed dasatinib and their caregivers. The program is accessible through www.sprycel.com or 1-855-SPRYCEL, and it includes:

  • Patient support coordinators
  • 1-month free trial with Sprycel One Card for new, eligible Medicare, Medicaid, or cash patients*
  • $0 monthly copay offer with Sprycel One Card for eligible commercially insured patients (subject to an annual maximum benefit of $32,000)*
  • Educational resources for patients with Philadelphia chromosome–positive CML

* Subject to terms and conditions of program, which are available through 1-855-SPRYCEL or visiting www.sprycel.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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