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ASCO Dasatinib in pediatric CML patients report

Asco CML pediatric 1

The 2017 American Society of Clinical Oncology (ASCO) Annual Meeting were taking place June 2–6 in Chicago.

At ASCO, Lia Gore, MD, co-director of the Hematological Malignancies Program at the University of Colorado Cancer Center and pediatric oncologist at Children’s Hospital Colorado, presented exciting data about Dasatinib in pediatric CML patients: CML in children is ultra-rare, making it very difficult to study - CML cases make up only 3% of all leukemias in children.

The data presented here has been submitted to FDA and EMA for the approval in pediatric use, and is quite impressive: The side effect profile seems to be very favourable and the inhibition of bone growth in children on TKIs seems to be less of an issue in Dasatinib than in Imatinib

However, given that administration of medicines in children and being adherent to therapy is often a challenge for young CML patients (and their parents), the availability of Dasatinib also as a powder-based suspension as well as the fact that the drug can be taken without or with food may make life much easier.

The investigators concluded that Dasatinib may be considered as a new standard of care for pediatric CML patients. 

 

ASCO DASATINIB IN PEDIATRIC CML PATIENTS REPORT

 

At the moment, newly diagnosed patients are usually treated with the only approved TKI in Imatinib, with about 51-61% of patients achieving a complete cytogenetic response, and about one third achieving an MMR

So far there has been very limited data on how to treat children in the Imatinib-resistant or intolerant setting - none of the second generation TKIs is currently approved for second line use in pediatric patients. The data presented at ASCO today however may change this, given BMS has filed approval with EMA and FDA in May 2017, based on the data presented today. In this Phase 2 open-label non-randomized study, pediatric patients with intolerance and resistance to imatinib as well as newly diagnosed CML patients were enrolled.

113 patients (age range 1.4 to 17.8 years) were enrolled in this study, with 2% being below 2 years of age, 45% of 2-12 years, and 52% of 12-18 years. 75 patients are still on treatment while the other patients had to discontinue treatment due to progressive disease, drug toxicity, patient withdrawal, maximum clinical benefit and other reasons.

Impressively, 55% of patients achieved a complete cytogenetic response within 6 months of Dasatinib therapy in all four arms of the study, and within 24 months, 55% of all imatinib-resistant/intolerant CML patients and 70% of all first-line patients achieved MMR within 24 months. 78% of patients on Dasatinib after resistance and intolerance and 93% of first-line patients on Dasatinib were free of progression at 48 months. Reaponse rates continued to increase over time.

The rares of drug-related adverse events was very similar in all arms of the study, but only a very small number of patients had to discontinue treatment due to side effects. While a small proportion of patients had side effects like Nausea (20%), myalgia (10%), fatigue (11%), rash (19%), diarrhea (18%), hemorrhage (10%), only one patient developed a severe form of the side effect. 17 patients had shown some impact on bone growth, but none of them in a severe form. There were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension or pulmonary arterial hypertension related to Dasatinib - which are side effects frequenlty seen in adults, especially at higher ages, on Dasatinib therapy.

All in all, early and durable responses were observed, and all study objectives were met. Safety of dasatinib in pediatric use was comparable to previous reports in adults, but no cases of pleural effusion or pulmonary arterial hypertension observed in the pediatric population. Given the data on efficacy and safety, but also the advantages of once-daily dosing, administration with or without food, and liquid formulation suggest that Dasatinib could be considered as the new standard of care of pediatric patients with CML in chronic phase.

 
Jan Geissler
CML Advocates Network cofounder
 
  

 

ASCO2017


 
   
 

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