OncoAlert

Welcome to this OncoAlert Session Round Up during ASH24, focusing on Multiple Myeloma pharmacologic therapies.

GMMG-HD7 Trial (JCO Publication)
This phase 3 trial evaluated adding isatuximab (Isa) to the standard RVd (lenalidomide, bortezomib, dexamethasone) regimen in transplant-eligible patients with newly diagnosed multiple myeloma. Part 1 randomized 662 patients to Isa-RVd or RVd, followed by autologous stem cell transplantation and a second randomization to lenalidomide or Isa-lenalidomide maintenance. Isa-RVd showed higher minimal residual disease (MRD) negativity rates post-transplant (66% vs 48%) and improved progression-free survival (PFS) with a hazard ratio of 0.70 (P = .0184). Isa-RVd plus lenalidomide maintenance further improved PFS (P = .016), underscoring Isa’s role in prolonging MRD negativity and PFS.

IMROZ Trial (Phase 3)
This trial analyzed Isa-VRd (isatuximab, bortezomib, lenalidomide, dexamethasone) versus VRd in transplant-ineligible patients with newly diagnosed multiple myeloma. Isa-VRd led to significant improvements in PFS and deeper, sustained MRD negativity, with 68.6% achieving MRD negativity by month 36 compared to 50.8% in the VRd group. Isa-VRd also resulted in lower MRD loss rates during maintenance and improved conversion from MRD positivity to negativity, leading to longer PFS. These findings highlight Isa-VRd’s potential for faster, durable responses and support its use to improve long-term outcomes in these patients.

UK MRA Myeloma XI+ Trial
The phase 3 UKMRA/NCRI Myeloma XI+ trial compared KRdc (carfilzomib, lenalidomide, dexamethasone, cyclophosphamide) to sequential triplet therapies (CRd, CTd) in newly diagnosed multiple myeloma patients. After a median follow-up of 102 months, KRdc improved PFS (56 vs 37 months, hazard ratio 0.69, P < 0.001) across cytogenetic risk groups, with higher MRD negativity rates. Early MRD negativity correlated with better PFS. While overall survival was similar in contemporaneously randomized patients (76% vs 71% at 60 months), non-contemporaneous controls showed an overall survival benefit with KRdc (76% vs 68%, hazard ratio 0.80, P = 0.011). These results emphasize the depth of responses with KRdc, particularly for high-risk patients, and the importance of early MRD negativity for improved PFS and survival.

DREAMM-7 Trial (Phase 3)
This trial compared belantamab mafodotin (BVd) versus daratumumab (DVd), both combined with bortezomib and dexamethasone, in relapsed/refractory multiple myeloma. BVd demonstrated a significant PFS benefit (36.6 vs 13.4 months, hazard ratio 0.41, P < 0.00001), with higher complete response and MRD negativity rates (25% vs 10%). BVd also showed a longer response duration (35.6 vs 17.8 months) and early trends favoring overall survival (84% vs 73% at 18 months). Median overall survival was not reached, but projections estimate 84 months for BVd versus 51 months for DVd. BVd's safety profile included manageable ocular events, positioning it as a promising option for relapsed/refractory multiple myeloma after first relapse.

AQUILA Trial (NEJM Publication)
This phase 3 trial evaluated subcutaneous daratumumab as monotherapy versus active monitoring in high-risk smoldering multiple myeloma. Among 390 patients, daratumumab reduced the risk of progression or death by 51% compared to monitoring (hazard ratio 0.49, P < 0.001) after a median follow-up of 65.2 months. At five years, PFS was 63.1% in the daratumumab group versus 40.8% in the monitoring group. Overall survival was higher with daratumumab (93.0% vs 86.9%). Daratumumab was well-tolerated, with hypertension being the most common grade 3 or 4 adverse event (5.7%), and no new safety concerns emerged. Daratumumab significantly delayed progression to active multiple myeloma and improved survival in high-risk patients.

Disclosure: Supported by Sanofi.