I'm pleased to speak about our multicentre phase III trial, GMMG-HD7, which is a two-part trial which included more than 660 patients. For part one of the trial we compared isatuximab induction in combination with lenalidomide, bortezomib and dexamethasone to lenalidomide, bortezomib and dexamethasone alone. Induction therapy  duration was 18 weeks and thereafter patients could receive  or received a high dose melphalan therapy followed by autologous blood stem cell transplantation. If patients had less than a complete response or high-risk disease, they could opt for a tandem transplant.

The trial then went on with a second part where we randomized patients to a maintenance strategy, either with the standard of care, lenalidomide, or lenalidomide plus isatuximab for up to three years. So the trial has two independent primary endpoints. The first primary endpoint was MRD negativity rates after induction therapy, and that has already been published in 2022. At the current data cutoff we will report on the progression-free survival from this first randomization. The second  primary endpoint of the trial is progression-free survival from the start of maintenance therapy, comparing the two maintenance strategies, and we will report on this when data are mature.

What are the key results?

At the current data cutoff we looked at two important new findings. First, we saw that the rates of MRD negativity in both arms increased post-transplant with a greater increase  in the patients that received isatuximab RVd as induction therapy with approximately 70% of the patients achieving MRD negativity in the bone marrow post-transplant as compared to 48% of the patients achieving MRD negativity in the RVd group.

The second and most important outcome is  the progression-free survival from first randomisation at a median follow-up of 48 months from first randomisation. Isatuximab RVd as compared to RVd induction therapy reduced the risk of progression or death by 30%, which is clinically significant and meaningful. We observed that this was also the case in most clinically relevant predefined subgroups and on a multi-variable analysis and on a sensitivity analysis where we waited for  the second randomisation.

What is the clinical significance of these results?

These results are highly significant for our clinical practice and our patients since they show that a quadruplet regimen consisting of isatuximab, bortezomib, lenalidomide and  dexamethasone leads to a prolonged progression-free survival even after only 18 weeks of induction therapy. This prolongation of PFS was independent on the second randomisation where patients received either lenalidomide or lenalidomide and isatuximab, and it was also achieved without an additional consolidation treatment post-transplantation.

So I think these results really underscore that quadruplet induction therapy is the standard of care in patients with newly diagnosed multiple myeloma who are eligible for an autologous stem cell transplantation.