GMMG-HD7: Isatuximab plus lenalidomide, bortezomib, dexamethasone as induction therapy for transplant-eligible NDMM

Previously, the randomized phase III GMMG-HD7 study showed that the addition of isatuximab (isa) to induction therapy with lenalidomide, bortezomib and dexamethasone (RVd) significantly increased the rate of MRD negativity after three cycles of therapy in patients with transplant-eligible, newly diagnosed multiple myeloma (NDMM).1 During the 2024 annual EHA meeting, MRD and response data were presented after intensification with high-dose therapy (HDT) and an autologous stem cell transplantation (ASCT).2 To talk us through these data we consulted Dr Fredrik Schjesvold, director of the Oslo Myeloma Center at the Oslo University Hospital in Norway.

In GMMG-HD7, 662 patients with transplant-eligible NDMM were randomized to receive three cycles of induction therapy with Isa-RVd or RVd. After induction, patients underwent a cyclophosphamide-based stem cell collection and subsequently proceeded to HDT with melphalan (200mg/m2) and an ASCT. For patients who did not achieve a complete response (CR) after the first ASCT and for patients with high-risk cytogenetics, a second ASCT was recommended. In phase 2 of the study, patients were randomized to receive maintenance therapy with either lenalidomide alone or in combination with Isa for up to 36 months.1,2

Following induction therapy, the rate of MRD-negativity (10-5) was reported at 50.1% in the Isa-RVd arm as compared to 35.6% with RVd alone (p< 0.001). In total 304 (91.8%) patients in the Isa-RVd arm completed at least one HDT/ASCT course, while this was the case for 278 (84.5%) of patients treated with RVd alone. After HDT/ASCT, the MRD-negativity rate (10-5) in the Isa-RVd arm had increased to 66.2%, while this reached 47.7% in the control arm (OR[95%CI]: 2.13[1.56-2.92]; p< 0.001).2 As such, more patients converted to MRD-negativity following HDT + ASCT after Isa-RVd induction therapy compared to RVd alone.2

The GMMG-HD7 study is still ongoing, and the second phase of the trial will now assess the role of Isa in combination with lenalidomide as maintenance therapy.