Updated survival outcomes of pomalidomide/bortezomib/dexamethasone in newly diagnosed multiple myeloma with renal impairment: A prospective, open-label, multicenter, phase 2 study

Abstract

Abstract BACKGROUND Renal impairment (RI) affects 20-40% of newly diagnosed multiple myeloma (NDMM) patients and independently predicts adverse survival. Bortezomib-based triplet regimens (doxorubicin, cyclophosphamide or thalidomide with dexamethasone) have been recommended for multiple myeloma (MM) with RI by International Myeloma Working Group (IMWG). However, these confer only limited survival benefits in such patients, with a reported 2-year overall survival (OS) of ~58%. Novel regimens that simultaneously target myeloma and reverse RI are critically needed. We previously reported at the ASH 2022 Annual Meeting and in Blood Advances (2023;7:7581-84) that PVD triplet therapy (pomalidomide/bortezomib/dexamethasone) in NDMM-RI achieved a 75.4% renal response rate at 3 months (best response 78.7%), without compromising stem cell harvest. Here, we present extended follow-up survival outcomes for this cohort. METHODS In this prospective, open-label, phase 2 trial (ChiCTR2100043748), 61 NDMM-RI patients (eGFR <40 mL/min) were enrolled at 28 Chinese centers (February 2021–January 2022). Key inclusion criteria included cast nephropathy, measurable disease, and no prior anti-myeloma therapy. Patients received up to 9 cycles of PVD induction (pomalidomide 4mg d1-14/21, bortezomib 1.3mg/m² on days 1, 4, 8, and 11 in the first two 21-day cycles and weekly in the following 35-day cycles, dexamethasone 20mg twice per bortezomib dosage) ± autologous stem cell transplantation (ASCT). The primary endpoint was 3-month renal response (IMWG criteria). Secondary endpoints included progression-free survival (PFS) and OS. Survival analyses were performed using the Kaplan-Meier method. RESULTS Of the 61 intention-to-treat patients, 33 (54.1%) completed the planned therapy (13 underwent ASCT, 20 received ≥6 PVD cycles). After a median follow-up of 42 months, 19 patients had disease progression and 17 had died. Causes of deaths were disease progression (n=8), non-MM comorbidities (n=5), and unknown causes (n=4). No new long-term safety signals emerged during the follow-up period. Among the entire PVD cohort (n=61), 57 patients had evaluable PFS data and 60 had evaluable OS data. Median PFS and OS were not reached after 42-month follow-up. The estimated 3-year PFS rate was 74.4% (95% CI: 61.9%-86.9%) and the estimated 3-year OS rate was 80.2% (95% CI: 69.6%-90.8%). Notably, patients achieving renal response had significantly superior OS compared to non-responders (HR 0.327, 95% CI: 0.120-0.893; P=0.029), highlighting renal recovery as a key prognostic factor of survival. CONCLUSION With extended follow-up, this study demonstrates that PVD induction offers survival benefit for NDMM patients with RI in addition to high renal response rates. Achieving renal recovery was strongly associated with improved OS.