Safety and Efficacy of New Drugs Combinations in Newly Diagnosed Multiple Myeloma with Renal Failure at Onset: A Retrospective Multicentric Study

Abstract

Renal injury at onset of newly diagnosed multiple myeloma (NDMM) is associated with poor outcome. Patients with severe renal failure due to MM are excluded from clinical trials with new drugs. The aim of this retrospective study was to describe the clinical characteristics, the treatment choices, the efficacy and the incidence of treatment-related toxicities of NDMM patients with renal insufficiency. We enrolled all NDMM patients with renal failure due to the disease treated at our Centers from 2012 to present. Fifty-one patients with a median age of 75 years were included; 76% had an International Staging System (ISS) of 3; 76% had anemia, 74% bone lesions and 30% had hypercalcemia; 31% had micromolecular myeloma. Thirty seven percent of patients had severe renal failure requiring dialysis treatment. Thirty-five percent of patients received treatment according to a VMP (Bortezomib, Melphalan and Prednisone) scheme, 20% received a triplet including Bortezomib and an immunomodulatory drugs (IMIDs) and 33% received a regimen including Daratumumab. The remaining 12% received a douplet (lenalidomide-dexamethasone or melphalan-prednisone). Thirty one percent of patients underwent an autograft procedure. Overall response rate (ORR) was 94% with a complete response (CR) rate of 17%. In terms of recovery of renal function, 50% achieved at least minimal renal response according to IMWG criteria, with 40% obtain a complete recovery of renal function. Patients who received more innovative treatment (regimens containing Daratumumab or Bortezomib in combination with IMIDs) achieved a response rate superior than very good partial response (≥ VGPR) of 74% with hematologic, neurologic, and infectious toxicities grade ≥ 3 of 22%, 7%, and 26%, respectively. Patients who received therapy with VMP or douplet had response rates ≥ VGPR of 25% with hematologic, neurologic, and infectious toxicity grade ≥ 3 rates of 29%, 4%, and 21%, respectively. Complete renal response rates in these two groups of patients were 45% and 20%, respectively. No death due to toxicity was registered. Patients with NDMM with renal failure at onset had a high burden of disease with unfavorable prognostic features. Although the small numbers of the cohort and the retrospective nature of this study it can be concluded that these patients can received new drugs combinations treatments with excellent response rates and without increased toxicity.