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Molecular Responses in Patients with Chronic Myelogenous Leukemia in Chronic Phase Treated with Imatinib Mesylate

Authors' Affiliations: Departments of¹ Leukemia, ² Bioimmunotherapy, and ³ Laboratory Medicine, the University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Jorge Cortes, Department of Leukemia, the University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030. Phone: 713-794-5783; Fax: 713-794-4297; E-mail: jcortes{at}mdanderson.org.

Purpose: To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib.

Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CML in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN- failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months).

Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio <0.05%) was achieved in 174 (62%), and transcripts became undetectable (complete molecular response) in 95 (34%). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5%) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37%) among those who did not achieve this response (P < 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A >1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response.

Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.

Key Words: Imatinib • Molecular responses • Chronic myeloid leukemia • PCR • Leukemias and lymphomas

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