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Lack of Cytogenic Response to Imatinib Linked to Poor Survival in Chronic Myeloid Leukaemia

Chronic myeloid leukaemia (CML) patients who fail to show a cytogenetic response to imatinib treatment may have shorter survival and shorter progression-free survival than patients receiving conventional treatment, according to new research.

"Our results suggest that previously untreated patients who do not achieve cytogenetic responses should be offered alternative treatment at an early stage," says David Marin, MD, Hammersmith Hospital, London, UK and colleagues.

Previous to imatinib availability, interferon alpha was considered the standard treatment for CML patients in chronic phase who were ineligible for allogeneic transplant. To assess survival advantage, the researchers compared the outcome of chronic-phase CML patients unresponsive to interferon alfa who were switched to imatinib with the outcome of patients receiving conventional therapy.

The imatinib-treatment group consisted of 143 chronic-phase CML patients who received therapy at the Hammersmith Hospital as part of multicentre phase-II clinical trials. The group receiving conventional chemotherapy (busulphan or hydroxyurea) consisted of 246 chronic-phase CML patients treated in the UK Medical Research Council's CML 3 trial.

Patients in both treatment groups met the same criteria for nonreponsiveness to interferon alfa.

Overall, results indicated that patients treated with imatinib had a survival advantage compared to the group receiving conventional treatment (relative risk [RR] of 0.54, 95% CI 0.31-0.93, P=0.026). Similar results were observed in the analysis of progression-free survival (RR 0.40, 0.20-0.77, P=0.0065).

While patients who received imatinib and achieved at least a partial cytogenetic response after 6 months (76 patients) had better survival compared to patients receiving conventional treatment, patients showing no cytogenetic response to imatinib (64 patients) had significantly worse survival.

"These findings lend support to the notion that a cytogenetic response to imatinib can be regarded as a robust surrogate marker for survival," the investigators concluded.

Lancet 2003 Aug 23;362:9384:617-9. "Survival of patients with chronic-phase chronic myeloid leukaemia on imatinib after failure on interferon alfa"

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