LOWER DOSAGE OF IMATINIB (IM) IS SUFFICIENT TO MAINTAIN COMPLETE MOLECULAR RESPONSE (CMR) IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS WITH LONG-TERM TOXICITY OF THE TREATMENT

ABSSUB-4512

Background: Continuation with imatinib (IM) treatment is currently the recommended strategy in all patients with CML and optimal treatment response. However, there is evidence that about 30% of patients may have problems with long-term side-effects symptoms burden. Information about the response in patients with molecularly undetectable leukemia (complete molecular response) CMR after IM in whom the dose should have been reduced in an effort to relieve from long-term toxicity is insufficient.

Aims: Safety and efficacy of IM dose reduction in patients with long-term toxicity and CMR after standard IM dosage was assessed in a retrospective fashion.

Methods: Files of all patients with CML treated with IM at our center were retrospectively analyzed for CMR, toxicity and dosage. 61 (29.8%) of 205 patients treated with first or second line IM with median follow-up 54 and 105 months respectively have achieved CMR. In 19 of them (31.2%; 13 females and 6 males aged 20-71; average m=47 years at diagnosis) the dose of IM was reduced due to toxicity. Sokal score was low in 9, intermediate and high in 4 each and in 2 patients unknown. Patients achieved MMR and CMR after average 13.3 and 27.7 months respectively, 12 of them were pretreated with interferon-alpha. Duration of CMR before dose reduction was 16-123 (m=56.7) months. Reasons for the dose reduction comprised fluid retention, eye-lid swelling, hemorrhage into conjunctiva, hematologic toxicity, muscle cramps, dyspepsia and complications after surgery. Dose reduction was strictly individualized: in 3 patients IM was interrupted, 9 patients received 400mg once to five times a week, 6 patients 300mg three times weekly to daily and one patient was treated with 200mg of IM daily.

Results: After average observation period of 37 (9-84) months CMR has been maintained in 13 (68.4%) patients with lower dose of IM: in three of them with single elevations of BCR-ABL level to MMR. In two other patients the response fluctuates between CMR and MMR while continuation with lower dose. Three patients have lost CMR: one regained it on full-dose IM, two maintain MMR on standard or lower dosage. Only one patient has lost MMR after interruption of treatment: CMR was gained after standard dose of IM and is maintained on lower dose. In all patient, toxicity of the therapy was ameliorated during lower dosage. Even during intermittent treatment patients were able to achieve comparable plasma levels with those achieved on previous standard therapy.

Summary/Conclusion: CMR has been safely and efficiently maintained in 16 (84%) of our patients with CML suffering from long-term toxicity of IM using lower dosage regimens. One patient maintained CMR with full dose and 2 remaining patients have maintained MMR on lower IM dose. Lower or intermittent maintenance treatment with IM have lead to significant reduction of side-effects and cost burden and may serve as an option for the patients who relapse after stopping of IM in CMR. Larger prospective trials are necessary in order to confirm efficacy and safety of this strategy. Acknowledgements: Supported by grants IGA MZ ČR NT12218-4/2011 and UP LF-2013-004 and 2013-010.

Keywords: None

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