Addition of Elotuzumab to Lenalidomide, Bortezomib, and Dexamethasone Induction and Consolidation and Lenalidomide Maintenance Fail to Provide Survival Benefit Among Patients With Newly Diagnosed MM

Results from a randomized phase 3 trial suggested that the addition of anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone induction or consolidation and lenalidomide maintenance among patients with transplant-eligible, newly diagnosed multiple myeloma (MM) who are eligible for autologous HSCT did not provide clinical benefit.

This study included 564 adult patients (aged 18–70 years) with previously untreated, symptomatic MM, and a WHO performance status of 0 to 3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions. The modified intention-to-treat (ITT) population included 559 patients and the safety population measured 555 patients. The recorded primary end point was progression-free survival (PFS), analyzed in a modified ITT population.

Trial participants were randomly assigned 1:1:1:1 to 4 treatment groups. Induction therapy consisted of 4 cycles of 21 days each of lenalidomide, bortezomib, and dexamethasone (lenalidomide 25 mg orally on days 1 to 14; bortezomib 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1 to 2) or, lenalidomide, bortezomib, and dexamethasone induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1 to 2, and on days 1 and 11 for cycles 3–4; elotuzumab-lenalidomide, bortezomib, and dexamethasone).

Autologous hematopoietic stem-cell transplantation (HSCT) was followed by 2 cycles of 21 days each of either lenalidomide, bortezomib, and dexamethasone consolidation (lenalidomide 25 mg orally on days 1 to 14; bortezomib 1.3 mg/m² subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus lenalidomide, bortezomib, and dexamethasone consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15). This was followed by maintenance therapy with either lenalidomide (10 mg orally on days 1 to 28 for cycles 1–3; then, up to 15 mg orally on days 1 to 28; lenalidomide, bortezomib, and dexamethasone/lenalidomide or elotuzumab-lenalidomide, bortezomib, and dexamethasone/lenalidomide group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1 to 6, and on day 1 for cycles 7 to 26; lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide or elotuzumab-lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide group) for 2 years. 

Trial results demonstrated that after a median follow-up of 49.8 months (IQR 43.7–55.5), there was no difference in PFS between the 4 treatment groups (adjusted log-rank P value, P = 0.86), and 3-year PFS rates were 69% (95% confidence interval [CI], 61 to 77), 69% (61 to 76), 66% (58 to 74), and 67% (59 to 75) among patients treated with lenalidomide, bortezomib, and dexamethasone/lenalidomide, lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide, elotuzumab-lenalidomide, bortezomib, and dexamethasone/lenalidomide, and elotuzumab-lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide, respectively. 

Infections, measured as grade 3 or worse, were the most frequently observed adverse event among all of the treatment groups. Serious adverse events, measured as grade 3 or worse, were observed in 68 (48%) of 142 participants in the elotuzumab-lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide group, 53 (39%) of 137 in the lenalidomide, bortezomib, and dexamethasone/lenalidomide group, 53 (38%) of 138 in the lenalidomide, bortezomib, and dexamethasone/elotuzumab-lenalidomide group, and 50 (36%) of 138 in the elotuzumab-lenalidomide, bortezomib, and dexamethasone/lenalidomide (36%) group. Additionally, there were 9 treatment-related deaths during the study. 

Elias K Mai, MD, Heidelberg Myeloma Center, University Hospital Heidelberg, Heidelberg, Germany, and colleagues concluded, “[The] addition of elotuzumab to [lenalidomide, bortezomib, and dexamethasone] induction and consolidation, and lenalidomide maintenance did not improve survival outcomes in patients with newly diagnosed multiple myeloma who are eligible for an autologous HSCT.”

Source:

Mai E, Goldschmidt H, Miah K, et al. Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): Results from a randomized, phase 3 trial. Lancet Hematol. Published online February 2024. doi: 10.1016/S2352-3026(23)00366-6