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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3388-3389.
Ph+ ALL: another success for imatinibOREGON HEALTH & SCIENCE UNIVERSITY
A study by Lee and colleagues demonstrates that the incorporation of imatinib with chemotherapy and allogeneic stem cell transplantation in the management of patients with Ph+ ALL may be the optimal treatment strategy.
Imatinib mesylate is an inhibitor of the protein tyrosine kinase domain associated with breakpoint cluster region–Abelson oncogene locus (BCR-ABL) and has been shown to have limited—albeit brief— single-agent activity in relapsed or refractory Ph+ ALL.2 Recently, a prospective study incorporating imatinib within the hyper-CVAD (cyclophosphamide, vincristine, infusional doxorubicin [Adriamycin], and dexamethasone) regimen has offered a new option for patients with Ph+ ALL, providing higher response rates and excellent tolerability and allowing patients to pursue transplantation.3
In this issue of Blood, Lee and colleagues present data from their phase 2 prospective study on allogeneic transplantation for newly diagnosed Ph+ ALL patients who have been induced with combination chemotherapy and imatinib mesylate. The results are quite remarkable when compared to both their own historical controls and clinical studies conducted over the past 2 decades.1 In this prospective trial, Lee and colleagues administered sequential chemotherapy and imatinib to 29 patients prior to transplantation. Although the follow-up period was relatively short, with a median duration of 25 months, the 3-year estimated probability of disease-free survival and overall survival were both 78%, with an estimated relapse rate of only 4%. In addition, the authors used molecular monitoring to detect any evidence of residual leukemia after transplantation, and they used these data to guide the withdrawal of immunosuppressants. Graft-versus-host disease (GVHD) was often encountered with forced immunosuppression taper, with what appears to be a definable graft-versus-leukemia (GVL) effect, an observation that has been difficult to demonstrate in aggressive ALL.4
This study involved a small group of patients and has not been followed for long, but given the imatinib combination therapeutic trials for Ph+ ALL conducted by Thomas et al3 and Towatari et al,5 it is highly unlikely that randomized trials assessing the efficacy of imatinib in Ph+ ALL will ever be performed. From now on, imatinib should be considered part of the standard induction regimen and overall management for patients with Ph+ ALL. What remains available to clinical investigation is the determination of the optimal schedule and dosage of imatinib in this disease. References
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| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
