CML Blast Phase Outcomes Remain Poor in TKI Era, Prognostic Factors Identified

Patients with chronic myeloid leukemia in the blast phase (CML-BP) pose a significant therapeutic challenge and have poor survival, even in the tyrosine kinase inhibitor (TKI) era, according to a new study.

“With the widespread of use of TKIs for the treatment of patients with CML, the risk of transformation to blast phase has markedly decreased,” wrote study authors led by Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston. Still, a “significant minority” of patients will have their disease transform to blast phase, and the predictive features of this transformation have not been well studied in the TKI era.

In this study, researchers analyzed data from 477 patients at MD Anderson with CML-BP who were treated with a TKI at some point during the course of their disease. Of those, 343 (72%) were treated with a TKI before developing CML-BP. Patients had a median age of 53 years, and 64% of those included were male. Results of the analysis were published online ahead of print in Cancer.

Most patients were diagnosed with CML in the chronic phase (80%), while de novo CML-BP occurred in 71 patients (15%). Of 426 evaluable patients treated for CML-BP, 149 (35%) were initially treated with a TKI alone, 195 (46%) were treated with TKI along with chemotherapy, and 82 (19%) were treated with other non-TKI therapies.

The median follow-up for the CML-BP patients was 11.5 months, and the median overall survival was 12 months. The median failure-free survival was 5 months, with 87% of patients failing their first-line treatment.

A multivariate analysis revealed a number of factors that were predictive of overall survival in CML-BP. Myeloid immunophenotype yielded poorer survival than lymphoid immunophenotype, with a hazard ratio (HR) of 1.70 (95% CI, 1.30–2.22; P < .001). The presence of a chromosome 15 aberration was also predictive of poorer overall survival, with an HR of 2.20 (95% CI, 1.12–4.32; P = .021), as was prior TKI therapy with an HR of 1.51 (95% CI, 1.14–2.00; P = .004). Stem cell transplantation (SCT) after transformation to blast phase and platelet count of 102 K/µL or higher were associated with improved survival, while age of 58 years or older and lactate dehydrogenase level of 1,227 IU/L or higher were associated with poorer survival.

This study, the authors wrote, “identifies novel leads into the prognostication and survival outcomes of patients with CML-BP in the TKI era. Treatment with a combination of TKIs and chemotherapy followed by SCT remains the backbone of treatment in these patients.” They added that new treatments specifically designed to address the molecular complexity of CML-BP are needed.