ASH 2024 | Isa-RVd induction therapy in patients with newly diagnosed multiple myeloma: the GMMG-HD7 trial

So GMMG-HD7 is a large randomized multi-center Phase III trial which has two parts and in this trial we included over 660 patients. So the trial has two separate parts. In the first part we compared induction therapy regimen with isatuximab, lenalidomide, bortezomib dexamethasone as compared to lenalidomide bortezomib and dexamethasone alone. Induction therapy was given for 18 weeks and thereafter the patients could receive a high dose melphalan followed by autologous blood stem cell transplantation and in case that the patients achieved less than a complete response or had high-risk disease features they could opt for a tandem transplantation. Thereafter second part of this trial starts where patients are being randomized to maintenance therapy with either lenalidomide alone, which is the current standard of care, or lenalidomide plus isatuximab. The trial has two independent primary endpoints, and the first primary endpoint has been published in 2022 and demonstrated that the MRD negativity rates with isa-RVD were significantly higher as compared to RVD alone after induction treatment. And the second part of the trial, the second primary endpoint, looks at the progression-free survival from the start of maintenance therapy and will be reported when data are mature. In the current follow-up here at ASH 2024, we looked at the progression-free survival from the first part of the study, so looking at the induction therapy effect, and this included all the 662 patients that were randomized. First, what we observed is that the MRD negativity rates continued to deepen post-transplant with almost 70% of the patients being MRD negative in the isa-RVD group as compared to 48% in the RVD group. And then we found that after a median follow-up of 48 months this translated into a significant progression-free survival benefit for patients treated with isa-RVD as compared to RVD without any additional consolidation and regardless of the second randomization. Patients in the isa-RVD group had a 30% risk reduction for progression or death as compared to RVD alone. We then also looked at clinically relevant subgroups and we found that most patients in clinically relevant subgroups benefited from the addition of isatuximab plus RVD and we also conducted a weighted risk set analysis on progression-free survival where we looked at the maintenance therapy with lenalidomide only and we could confirm the benefit of the induction therapy with isatuximab as compared to RVD in this patient subgroup. We then went on and looked at the effect of MRD negativity and we could show that independent of the treatment that patients received, if they achieved MRD negativity they had a better prognosis, though more patients with isa-RVD as compared to RVD achieved an MRD negativity. And we could also show that among patients who were MRD positive, the addition of isatuximab to induction therapy resulted in a better outcome as compared to RVD alone. So overall, this trial is the first to show that a quadruplet regimen induction therapy for up to 18 weeks without an additional consultation post-transplant and regardless of a second maintenance improved progression-free survival independent on the maintenance strategy. And in the next part of the trial, we wait for the data and hopefully we will see the progression-free survival results from part two of the trial and the study has just been published in the Journal of Clinical Oncology as open access paper so please if you like you can access it and read the whole story.

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