The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2–3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).
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This work has been supported in part by grants RD12/0036/0046 and PI12/1093 from Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), and 2014SGR-552 from AGAUR (Generalitat de Catalunya).
JB, LR, JJL and JSM designed the trial; all authors performed the research; AO performed the statistical analysis; LR and JB analyzed and interpreted the data; LR wrote the initial draft of the manuscript; JB, AO, MVM, JJL and JSM reviewed the draft manuscript; and all authors approved the final version for submission.
LR received honoraria from Janssen and Celgene, AO has served as member of advisory boards for Janssen and Celgene, MVM has served as member of advisory boards for Celgene, Janssen and Millenium, JJL received honoraria from Janssen and Celgene, JSM discloses consultation fees from Celgene, Janssen and Millenium, and JB received grant support from Janssen and received honoraria from Janssen and Celgene. The remaining authors declare no conflict of interest.
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Rosiñol, L., Oriol, A., Teruel, A. et al. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia 31, 1922–1927 (2017). https://doi.org/10.1038/leu.2017.35
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