Conditioning with melphalan at 200 mg/m2 (MEL200) produces similar outcomes as conditioning with busulfan plus melphalan (BUMEL) in patients with newly diagnosed multiple myeloma (NDMM), according to final results of a phase 3 trial.

At 7 years, there were no significant differences in progression-free survival (PFS) or overall survival (OS) between the BUMEL and MEL200 groups.

These results were presented at the 19th International Myeloma Society Annual Meeting by Juan José Lahuerta Palacios, MD, of Hospital Universitario 12 de Octubre in Madrid. 


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This phase 3 study, GEM12menos65, enrolled patients with NDMM who were 65 years of age or younger and had measurable disease, an ECOG performance status of 0-2, and adequate organ function. 

Patients were randomly assigned to receive conditioning with MEL200 (n=228) or BUMEL (n=230) before autologous stem cell transplant (ASCT). There were no significant differences in baseline characteristics between the treatment arms.

Patients in both arms received lenalidomide, bortezomib, and dexamethasone for induction (6 cycles) and consolidation (2 cycles). For conditioning in the BUMEL arm, patients received a cumulative dose of 9.6 mg/kg of busulfan and 140 mg/m2 of melphalan. 

For ASCT, patients received a median of 3×106 CD34+ cells/kg in the BUMEL group and 3.1×106 CD34+ cells/kg in the MEL200 group. Maintenance therapy consisted of lenalidomide and dexamethasone, with or without ixazomib. 

Results

In the intent-to-treat population, response rates and rates of minimal residual disease negativity were similar with BUMEL and MEL200 after induction, transplant, and consolidation. Granulocyte and platelet recovery times after ASCT were similar between the groups as well.  

After induction, the rate of complete response (CR) was 42.2% in the BUMEL group and 30.3% in the MEL200 group. After transplant, the CR rates were 53.5% and 43.0%, respectively. After consolidation, CR rates were 59.1% and 53.1%, respectively.

The primary endpoint was PFS. At a median follow-up of 84.4 months, PFS results were similar between the BUMEL and MEL200 groups (hazard ratio [HR], 0.880; 95% CI, 0.679-1.139; P =.331). 

The 7-year PFS rate was 50.6% in the BUMEL group and 46.2% in the MEL200 group. The median PFS was not reached in the BUMEL group and was 75.3 months in the MEL200 group. 

OS outcomes were also similar between the treatment groups (HR, 1.059; 95% CI, 0.744-1.509; P =.750). The 7-year OS rate was 73.4% in both groups, and the median OS was not reached in either group. 

Subgroup analyses suggested a PFS benefit with BUMEL for patients with stage 3 disease, t(14;16), and/or del(1p). A multivariate analysis suggested a PFS benefit with MEL200 for patients with no cytogenetic abnormalities. 

Grade 1 gastrointestinal toxicities were more common with BUMEL than with MEL200 (21.8% vs 10.8%), as was grade 3 mucositis (17.8% vs 9.8%). Other reported nonhematologic toxicities occurred at similar rates in both groups.

Disclosures: The presenter declared affiliations with Celgene/Bristol Myers Squibb, Sanofi, Takeda, Amgen, Janssen, and Oncopeptides.

Reference

Lahuerta Palacios JJ, Jiménez Ubieto A, Rosiñol L, et al. BUMEL vs MEL-200 prior autologous transplant for patients with newly diagnosed multiple myeloma previously treated with bortezomib, lenalidomide and dexamethasone: Final results of a phase 3 trial. Presented at IMS 2022; August 25-27, 2022; Abstract OAB-040.