Updates from GMMG-HD7

Isatuximab-RVd as induction therapy for patients with transplant-eligible, newly diagnosed multiple myeloma.

One of the oral abstract sessions at ASH 2024 on multiple myeloma (MM) featured two presentations with updates from the randomized phase III GMMG-HD7 study.1,2 In this video, Dr Elias Mai, haematologist at the Heidelberg University Hospital in Germany and one of the lead investigator of GMMG-HD7, shares the key take-aways of these abstracts.

GMM-HD7 is a multicentre, randomized-controlled phase III study in which 662 patients with transplant-eligible newly diagnosed MM were randomly assigned to receive induction therapy with either lenalidomide-bortezomib-dexamethasone (RVd), or RVd in combination with isatuximab (Isa). All patients subsequently received high dose melphalan and proceeded to an autologous hematopoietic stem cell transplant (ASCT). After this transplantation, patients entered a second randomization in which they were allocated to receive maintenance therapy with lenalidomide alone, or in combination with Isa.

Previously, it was shown that GMMG-HD7 met the first of its 2 co-primary endpoints by demonstrating a significantly higher rate of minimal residual disease (MRD) negativity in the bone marrow after induction therapy with Isa-RVd vs. RVd alone (50% vs. 36%; OR[95%CI]: 1.82[1.33-2.48], p<0.001). Updated results presented at ASH 2024 demonstrate that this higher rate of MRD negativity translates into a 30% lower risk for disease progression or death with Isa-RVd compared to RVd alone (HR[95%CI]: 0.70[0.52-0.94]).1 Importantly, this progression-free survival (PFS) benefit was maintained after correcting for the second randomization in the study.1

In a second GMMG-HD7 abstract, Mai and colleagues specifically looked at the impact of the MRD status on PFS. This analysis showed that MRD-negativity at the end of induction, continued MRD-negativity (i.e., MRD-negativity from post induction until post intensification) and post-transplant MRD-negativity were associated with a significantly better PFS across the two treatment arms. Importantly, however, the proportion of patients obtaining (continued) MRD-negativity was significantly higher with Isa-RVd than with RVd alone. Of note, also for patients who remained MRD positive at the end of induction, the addition of Isa to RVd led to a significantly longer PFS.2

As such, these updated results of GMMG-HD7 confirm the benefit of adding Isa to RVd induction in transplant eligible patients with newly diagnosed MM. As GMMG-HD7 is the only randomized controlled, phase III study in which the addition of an anti-CD38 antibody to lenalidomide maintenance is evaluated, the results of the second part of this trial are eagerly awaited.