Isatuximab Combo for Newly Diagnosed Multiple Myeloma: GMMG-HD7

When added to normal care for people with multiple myeloma (MM), anti-CD38 monoclonal antibodies have always shown better results. Researchers wanted to see how well isatuximab worked with lenalidomide, bortezomib, and dexamethasone in people with recently diagnosed MM who were eligible for a transplant. This open-label, multicenter, randomized, active-controlled, phase III trial was done at 67 academic and oncology practice sites in Germany. This study is still going on and is split into two parts. Here, researchers talk about the results of Part 1. Patients who were eligible were between the ages of 18 and 70, had a confirmed diagnosis of untreated multiple myeloma that needed systemic treatment, and had a WHO performance status between 0 and 2. They were also eligible for induction therapy, high-dose melphalan, autologous hematopoietic stem-cell transplantation, and maintenance treatment. For three 42-day cycles of induction therapy, patients were given either isatuximab plus lenalidomide, bortezomib, and dexamethasone (in the isatuximab group) or lenalidomide, bortezomib, and dexamethasone alone (in the control group). It was done using a web-based method and permuted blocks. Patients in both groups got lenalidomide (25 mg orally on days 1-14 and 22-35) and bortezomib (1·3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) and dexamethasone (20 mg orally on days 1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, and 32-33). Days 1, 8, 15, 22, and 29 of cycle 1 and days 1, 15, and 29 of cycles 2 and 3 saw the intravenous injection of isatuximab at a dose of 10 mg/kg. The main endpoint was the absence of minimal residual disease (MRD) as measured by flow cytometry in the group of people who wanted to be treated (ITT). The number for this study on ClinicalTrials.gov is NCT03617731. Between October 23, 2018, and September 22, 2020, 331 people in the isatuximab group and 329 people in the control group were part of the ITT analysis. 654 of the patients were white, which is 99%. Two were from Africa, one was from Arabic, and three were from Asia. 250 (38%) were female, and 410 (62%) were male.

The median age was 59 years (IQR 54-64). After induction treatment, MRD negativity was reached in 166 (50%) of the isatuximab group’s patients but only in 117 (36%) of the control group’s patients (OR 1·82 [95% CI 1·33-2·48]; p=0·00017). From the start of induction treatment to the end, the median follow-up time was 125 days (IQR 125-131) versus 125 days (125-132). At least one bad thing happened to 208 (63%) of the 330 patients, but only 199 (61%) of the 328 patients. Neutropenia of grade 3 or 4 happened to 77 (23%) patients instead of 23 (7%) patients, and grade 3 or 4 infections happened to 40 (12%) patients instead of 32 (10%) patients. During induction therapy, there were 12 deaths. One case of septic shock occurred in the isatuximab group, and four cases of cardiac decompensation, liver and renal failure, cardiac arrest, and drug-induced enteritis occurred in the control group as a result of treatment. The study included that Isatuximab combo enhances induction therapy in newly diagnosed transplantation-eligible multiple myeloma with improved MRD rates and safety profile.

Source:https://pubmed.ncbi.nlm.nih.gov/36328040/

Clinical Trial: http://clinicaltrials.gov/show/NCT03617731

Goldschmidt H, Mai EK, Bertsch U, Fenk R, Nievergall E, Tichy D, Besemer B, Dürig J, Schroers R, von Metzler I, Hänel M, Mann C, Asemissen AM, Heilmeier B, Weinhold N, Huhn S, Kriegsmann K, Luntz SP, Holderried TAW, Trautmann-Grill K, Gezer D, Klaiber-Hakimi M, Müller M, Khandanpour C, Knauf W, Scheid C, Munder M, Geer T, Riesenberg H, Thomalla J, Hoffmann M, Raab MS, Salwender HJ, Weisel KC; German-Speaking Myeloma Multicenter Group (GMMG) HD7 investigators. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): Part 1 of an open-label, multicentre randomized, active-controlled, phase 3 trial Lancet Haematol. 2022 Nov;9(11):e810-e821. doi: 10.1016/S2352-3026(22)00263-0. PMID: 36328040.