Transplant-eligible newly diagnosed multiple myeloma (NDMM) — University Hospital Heidelberg / German-Speaking Myeloma Multicenter Group (GMMG)
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Save the FISH - still a useful tool in clinal routine! GMMG-HD6 was an excellent trial. I never thought that Elotuzumab had no benefit in any treatment sequence! #ASH24 #mmsm https://t.co/1XxVrFeqMN
Impact of Clonal Heterogeneity in Newly Diagnosed, Transplant-Eligible Multiple Myeloma -- Subgroup Analysis of the GMMG HD6 Phase III Trial [Dec 7, 2024] Merz et al. #ASH24 Abst 84…
#ASH24 #mmsm
Oral myeloma: Impact of Clonal Heterogeneity in Newly Diagnosed, Transplant-Eligible Multiple Myeloma – Subgroup Analysis of the GMMG HD6 Phase III Trial
Subclones are common in…
GMMG-HD6 is the first and definitive Phase 3 trial showing that adding the SLAMF7 mAb elotuzumab to standard RVd induction/consolidation and lenalidomide maintenance does NOT improve PFS or OS in transplant-eligible NDMM. Results contrast with positive ELOQUENT-2 and ELOQUENT-3 trials in RRMM. Elotuzumab's role in myeloma remains limited to relapsed/refractory settings per ELOQUENT-3 (Elo-Pd) and ELOQUENT-2 (Elo-Rd). For NDMM, the landscape has moved toward anti-CD38 quadruplets: daratumumab-RVd (PERSEUS, GRIFFIN) and isatuximab-RVd (GMMG-HD7) — a stark contrast with GMMG-HD6's negative signal.
3-year PFS by arm rate: 69% (RVd/R) vs. 69% (RVd/E-R) vs. 66% (E-RVd/R) vs. 67% (E-RVd/E-R). Phase 3 4-arm randomized trial (N=555, randomized 1:1:1:1). Median follow-up 49.8 months (IQR 43.7-55.5). NO DIFFERENCE in PFS between the four arms: 3-year PFS rates 69% (RVd/R), 69% (RVd/E-R), 66% (E-RVd/R), 67% (E-RVd/E-R). Adjusted log-rank P=0.86. Adding elotuzumab to RVd induction/consolidation OR lenalidomide maintenance did NOT provide clinical benefit. Mai et al., Lancet Haematol 2024;11(2):e101-e113.
OS comparable across all 4 arms; no survival benefit from adding elotuzumab to any treatment phase. Trial concluded elotuzumab-containing therapies should be reserved for the relapsed/refractory setting (per ELOQUENT-2 and ELOQUENT-3).
Grade ≥3 adverse events: 20% (RVd_R) vs. 23% (RVd_E_R) vs. 25% (E_RVd_R) vs. 34% (E_RVd_E_R). Key AEs: Grade ≥3 infections (most common AE, all arms), Serious AEs (Grade ≥3): 48% (E-RVd/E-R), 39% (RVd/R), 38% (RVd/E-R), 36% (E-RVd/R). Grade ≥3 infection rates highest in the E-RVd/E-R quadruplet (34%) and lowest in RVd/R (20%). Nine treatment-related deaths total: RVd/R 2 (sepsis, toxic colitis); RVd/E-R 1 (meningoencephalitis); E-RVd/R 4 (pulmonary embolism, septic shock, atypical pneumonia, cardiovascular failure); E-RVd/E-R 2 (sepsis, pneumonia/pulmonary fibrosis).
❌ Negative Phase 3: Elotuzumab adds no benefit to RVd in transplant-eligible NDMM. GMMG-HD6 is the first and definitive Phase 3 trial showing that adding the SLAMF7 mAb elotuzumab to standard RVd induction/consolidation and lenalidomide maintenance does NOT improve PFS or OS in transplant-eligible NDMM. Results contrast with positive ELOQUENT-2 and ELOQUENT-3 trials in RRMM. Elotuzumab's role in myeloma remains limited to relapsed/refractory settings per ELOQUENT-3 (Elo-Pd) and ELOQUENT-2 (Elo-Rd). For NDMM, the landscape has moved toward anti-CD38 quadruplets: daratumumab-RVd (PERSEUS, GRIFFIN) and isatuximab-RVd (GMMG-HD7) — a stark contrast with GMMG-HD6's negative signal.
