Researchers affiliated with Children’s Oncology Group (COG) have reported that the addition of long-term daily Gleevec® (imatinib mesylate) to high-dose chemotherapy improves event-free survival (EFS) in children and adolescents with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). The details of this study were published online on October 8, 2009.[1] 

A small percentage of children and adolescents with ALL are PH+ (3-5%), which contrasts to 20% for patients between the ages of 20 and 60 years and 40% for patients over the age of 60 years. Previous studies in PH+ ALL in childhood have shown a 65% EFS following allogeneic stem cell transplant and 25% without an allogeneic stem cell transplant.

The AALL0031 study evaluated a regimen of Gleevec (340 mg/m2/d) with intensive chemotherapy in 92 patients’ ages one to 21 years with PH+ ALL. Therapy consisted of induction, reinduction, and intensive maintenance with Gleevec. Investigations could elect to remove patients from this study at six months to administer an allogeneic stem cell transplant from a related or unrelated donor and receive Gleevec maintenance after the transplant.

Patients in this study were exposed to an increasing number of days—42 to 280—of Gleevec therapy. Fifty patients in this study received 280 continuous days of Gleevec. Patients who had HLD identical siblings underwent an allogeneic stem cell transplant. Toxicity was compared to 65 patients receiving the same chemotherapy without Gleevec.

For the 50 patients who received 280 days of continuous Gleevec, EFS was 80% compared with 35% for historical controls. The 21 patients treated with a sibling donor transplant had a three-year EFS of 57%.

Gleevec did not increase the toxicity associated with intensive chemotherapy.

These authors stated that the main benefit of Gleevec appeared to be in children with the largest amount of residual disease after induction therapy.

Comments: Gleevec clearly improved the outcome of children with PH+ ALL compared with historical controls. The data is mature enough to state that allogeneic stem cell transplantation is not superior to Gleevec and chemotherapy. Further follow-up will be required for a final comparison of chemotherapy and Gleevec to stem cell transplantation.

Reference:

[1] Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive actue lymphblastic leukemia: A Children’s Oncology Group Study, Journal of Clinical Oncology [early online publication]. 2009; on October 8.