Olatoyosi Odenike, MD, of The University of Chicago, said the findings of the hyper-CVAD plus imatinib study were striking, given the wide difference in overall survival between the hyper-CVAD plus imatinib group and the historical cohort who received chemotherapy alone. "Although the CR rates were virtually identical (over 90%) between the two cohorts, the responses were more durable in the hyper-CVAD plus imatinib cohort. The 3-year CR duration rate was almost 70% in the imatinib cohort compared with 24% in the chemotherapy-alone arm. Patients were able to stay in remission for a longer time, and this translated into an improvement in overall survival," said Dr. Odenike, Assistant Professor in the Department of Medicine in the Section of Hematology and Oncology at The University of Chicago. Dr. Odenike presented the study results at the Best of ASCO Meeting in Boston.

Although the addition of imatinib to chemotherapy has now become a standard approach for treating Ph+ ALL, the M. D. Anderson study did provide important information with regard to long-term outcomes for this approach. It adds to data by other research groups confirming the long-term survival benefits of combining chemotherapy with a tyrosine kinase inhibitor (TKI) for Ph+ ALL, Dr. Odenike said. She noted that although a limitation of this study was the use of a historical cohort for comparison, a randomized study of chemotherapy with or without imatinib in Ph+ ALL would not be ethical, given the obvious benefits of TKIs in this disease.

Continued Role of Stem Cell Transplant

The findings of the MD Anderson study also suggest that allogeneic stem cell transplants cannot be dispensed with for Ph+ ALL patients, particularly younger patients-even in an era when imatinib has significantly extended the durability of complete remission, Dr. Odenike said. Whether the addition of second- or third-generation TKIs to chemotherapy in lieu of imatinib would further improve outcomes compared to chemotherapy plus imatinib remains an open question, she added.

"We know that it's feasible to add a second-generation TKI such as dasatinib to chemotherapy and to get good outcomes in Ph+ ALL," she said. "A randomized study would be required to determine whether dasatinib would be superior to imatinib in Ph+ALL. Dasatinib does have the potential additional advantage of crossing the blood-brain barrier." ■