Adding Elotuzumab to Triplet Therapy Provides ‘No Clinical Benefit’ in Newly Diagnosed Myeloma

The addition of elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) induction and consolidation therapy and lenalidomide maintenance therapy did not provide clinical benefit for transplant-eligible patients with newly diagnosed MM, according to results from the GMMG-HD6 trial.

The phase III, randomized trial was led by Elias Mai, MD, of the University Hospital Heidelberg in Germany, and published in The Lancet Haematology. The primary endpoint was PFS, while secondary endpoints included OS, rates of complete response after induction and consolidation therapy, time to progression, duration of response, and quality-of-life assessment.

The authors noted that the results were “in line with observations from the ELOQUENT-1 and SWOG-1211 trials.” They added that “the GMMG-HD6 trial complements the existing evidence on the use of elotuzumab” in this patient subgroup.

A total of 564 patients were randomly assigned to the following four treatment groups:

• In the RVd/R group, patients received RVd induction and consolidation followed by lenalidomide maintenance
• In the RVd/E-R group, patients received RVd induction, elotuzumab plus RVd consolidation, then elotuzumab plus lenalidomide maintenance therapy
• In the E-RVd/R group, patients received elotuzumab with RVd induction, RVd consolidation, then lenalidomide maintenance
• In the E-RVd/E-R group, patients received elotuzumab with RVd induction and consolidation, followed by elotuzumab plus lenalidomide maintenance

After a median follow-up of 49.8 months, there was no difference in PFS or OS between the four treatment groups. The three-year PFS rates were 69% (95% CI, 61-77) for RVd/R, 69% (95% CI, 61-76) for RVd/E-R, 66% (95% CI, 58-74) for E-RVd/R, and 67% (95% CI, 59-75) for E-RVd/E-R. The three-year OS rates were 89% (95% CI, 84-95) in the RVd/R group, 89% (95% CI, 84-94) in the RVd/E-R group, 93% (95% CI, 88-97) in the E-RVd/R group, and 90% (95% CI, 85-95) in the E-RVd/E-R group.

Furthermore, adding elotuzumab to induction, consolidation, or maintenance treatment did not result in improved time to progression or prolonged duration of response compared with RVd/R alone.

Grade 3 or higher AEs occurred in 68 (48%) patients in the E-RVd/E-R group, 53 (39%) in the RVd/R group, 53 (38%) in the RVd/E-R group, and 50 (36%) in the E-RVd/R (36%) group.

Nine treatment-related deaths occurred during the study: two in the RVd/R group that were considered lenalidomide related; one in the RVd/E-R group that was considered lenalidomide and elotuzumab related; four in the E-RVd/R group; and two in the E-RVd/E-R group that were considered lenalidomide- or elotuzumab-related.

“The addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed [MM] did not provide clinical benefit,” the authors wrote. “Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory [MM].”

Funding was provided by Bristol Myers Squibb/Celgene and Chugai.

Reference

Mai EK, 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 randomised, phase 3 trial. Lancet Haematol. 2024. doi:10.1016/S2352-3026(23)00366-6