Background: In multiple myeloma (MM), relapse is a problem after autologous hematopoietic stem cell transplantation (ASCT). In the nontransplant setting, thalidomide/dexamethasone/clarithromycin (BLT-D) and lenalidomide/dexamethasone/clarithromycin (BiRd) achieve responses with acceptable toxicity. Both regimens are reasonable objects of study in the post-ASCT setting. Patients and Methods: We report on BLT-D and BiRd given post-ASCT. Studies were conducted consecutively. After recovery from ASCT, therapy was started. All 3 drugs were given for 1 year, and then immunomodulatory drugs alone were given as long as tolerated or until disease progression. Results: For BLT-D, the most common toxicity was peripheral neuropathy (PN). For BiRd, infection, PN, and neutropenia were the most common adverse events. BiRd was associated with a higher frequency of secondary cancers. The median follow-up for BLT-D was 10.2 years (range 8.6-10.7) and for BiRd it was 7.5 years (range 6.4-8.4). After BLT-D, 18 patients (67%) were alive and 10 (37%) were alive without disease progression, and after BiRd, 18 patients (58%) were alive and 10 (32%) were alive without disease progression. Conclusions: BLT-D and BiRd can be given post-ASCT with different toxicity profiles and comparable disease-free and overall survival rates. A randomized study comparing these regimens to single-agent lenalidomide is needed to determine which approach is superior. Key Message: Relapse of MM is a major problem after ASCT. Strategies are needed post-ASCT to improve outcomes. In the nontransplant setting, thalidomide or lenalidomide/dexamethasone/clarithromycin treat MM with acceptable toxicity. We, thus, studied both regimens post- ASCT. They can be given with different toxicity profiles and result in good disease control.

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