Melphalan and Prednisolone Plus Thalidomide Compared to other Treatments for Multiple Myeloma in the Elderly

In a trial 1 447 patients aged 65-75 years with previously untreated myeloma were randomly assigned to receive either melphalan and prednisolone (MP) or melphalan and prednisolone plus thalidomide (MPT) or reduced-intensity stem cell transplantation usimg melphalan (MEL100). After a median follow-up of 51.5 months, median overall survival times were 33.2 months for MP, 51.6 months for MPT, and 38.3 months for MEL100, hazard ratio for overall survival favoring MPT 0.57 (95% CI 0.46 to 0.81, p=0.0006) against MP and 0,69 (95% CI 0.49 to 0.96, p=0.027) against MEL100. Relative improvement of disease-free survival was of similar magnitude. Deaths due to toxicity occurred in 4 patients in the MP, 6 patients in the MEL100, and no patients in the MPT group. Thrombosis or pulmonary embolism occurred in 12 patients (12%) treated with MPT. Neurotoxicity related to thalidomide was noted in more than half of the patients.

In another RCT 2 in newly diagnosed patients aged 65-85 years, MTP improved 2-year event-free survival (54% vs 27%), but did not significantly improve 3-year overall survival (80% vs 64%) compared with MP.

Comment: The risk of thromboembolism associated with thalidomide can be reduced by thromboprophylaxis, and the disability associated with neurotoxicity can be reduced by stopping the drug when moderately severe symptoms of neurotoxicity appear.

References

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