Subgroup Analysis of Phase 3 Trial GMMG-HD7 Evaluating Isa-RVd in Patients with High-Risk Cytogenetics

Previously reported results from the multicenter, phase 3 GMMG-HD7 study showed a significantly greater rate of minimal residual disease (MRD) negativity versus lenalidomide-bortezomib-dexamethasone (RVd) alone in newly diagnosed multiple myeloma (NDMM) patients. In this earlier analysis, the MRD-negativity rate of isatuximab (Isa)-RVd reached 50.1% at the end of induction versus 35.6% of patients with RVd alone.¹

At the 2022 European Hematology Association Congress, Mai and colleagues presented findings from a GMMG-HD7 subgroup analysis that evaluated the MRD-negativity rate after induction therapy on patients with high-risk cytogenetics. Transplant-eligible NDMM patients in both study arms were randomly assigned to receive three 42-day cycles of RVd; Isa was then added to RVd in 3 cycles. High-risk and ultra–high-risk cytogenetics were defined as ≥1 or 2 of the following aberrations: del17p, t(4;14), t(14;16), and gain1q21 (≥3 copies).²

A total of 660 patients were included in the intention-to-treat analysis: 331 received Isa-RVd and 329 received RVd. Of these, 45.2% of patients had high-risk cytogenetics and 14.1% had ultra–high-risk cytogenetics. The trial met its primary end point: Isa-RVd demonstrated superiority of MRD-negativity rates compared with RVd alone. In patients with high-risk cytogenetics, MRD-negativity rates were 50.4% with Isa-RVd compared with 37.4% with RVd (95% confidence interval [CI], 1.04-2.79; P = .03). In patients with ultra–high-risk cytogenetics, MRD-negativity rates were 56.3% versus 44.1% with Isa-RVd and RVd, respectively (95% CI, 0.67-3.99; P = .28). Researchers also noted that similar results were observed for Isa-RVd versus RVd among the common major single high-risk cytogenetic features: del17p: 56% versus 35.3%; t(4;14): 57.6% versus 47.1%; t(14;16): 66.7% versus 50.0%; gain1q21: 48.2% versus 35.6%. In addition, similar efficacy results were seen when dividing patients by either no high-risk aberration (standard risk), 1 high-risk aberration (high-risk), or ≥2 high-risk aberrations (ultra–high-risk).²

Overall, authors concluded that, in transplant-eligible NDMM patients with high-risk or ultra–high-risk cytogenetics, Isa-RVd induction therapy was superior to RVd alone. These results are consistent with the benefit that was observed in the overall trial population.²

Sources

1. Goldschmidt H, Mai EK, Nievergall E, et al. Addition of isatuximab to lenalidomide, bortezomib and dexamethasone as induction therapy for newly-diagnosed, transplant-eligible multiple myeloma patients: the phase III GMMG-HD7 trial. ^Blood. 2021;138(suppl 1):463.
2. Mai EK, Bertsch U, Fenk R, et al. Isatuximab, lenalidomide, bortezomib and dexamethasone as induction therapy for newly-diagnosed multiple myeloma patients with high-risk cytogenetics: a subgroup analysis from the GMMG-HD7 trial. Presented at: European Hematology Association Congress; June 9-17, 2022; Vienna, Austria.