Managing Chronic Myeloid Leukemia Treatment

Harry P. Erba, MD, PhD

Harry P. Erba, MD, PhD, associate professor, Department of Internal Medicine, University of Michigan Health System, discussed the management of chronic myeloid leukemia (CML) treatment at the 16th Annual International Congress on Hematologic Malignancies.

Erba noted that certain characteristics of patients with CML can affect therapeutic outcomes. For example, the deletion of derivative chromosome 9 is associated with the loss of tumor suppressor genes. This mutation can be detected through a FISH (fluorescent in situ hybridization) analysis.

In another example, Erba said patients with BCR-ABL kinase domain mutations commonly experience acquired resistance to imatinib mesylate (Gleevec), a standard of treatment for many patients with CML. The expression of these mutations can be monitored through the use of PCR (polymerase chain reaction) testing.

While these methods are fairly noninvasive, Erba suggests following the guidelines set forth by the National Comprehensive Cancer Network.

“I recommend a more thorough evaluation of the disease status at the time of diagnosis,” Erba said. “The patient should have a bone marrow biopsy. It gives you morphological evidence of accelerated phase with fibrosis or clustering of immature cells that might be important in choosing the right therapy.”

Erba said other mutations might be closely associated with patient response to tyrosine kinase inhibitors (TKIs), as demonstrated in the ENESTnd trial presented at ASCO 2011. ENESTnd demonstrated the superiority of nilotinib over imatinib in patients with newly diagnosed CML.

In the study, mutational analysis revealed that overall, the number of new mutations occurring in the imatinib arm was double the number in the 2 nilotinib arms. The occurrence of multiple BCR-ABL mutations and detection of T315I mutations (mutations associated with nilotinib and imatinib resistance) was similar across all treatment groups. Of note, incidence of disease progression to accelerated phase or blast phase was greater in patients with new mutations receiving imatinib than those receiving nilotinib, potentially suggesting nilotinib’s superiority for these patients.

Finding the right TKI inhibitor in earlier stages of the disease makes an enormous difference, Erba said. “The key to using TKI therapy is to prevent the progression to advanced stage disease.”

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