Background: High-dose therapy followed by autologous stem cell transplantation (ASCT) is the standard first line treatment for younger patients (<70 years) with multiple myeloma (MM). Approximately 20%–50% of all patients already display an impaired kidney function at diagnosis. However, MM patients with severe renal dysfunction are excluded from most ASCT studies. Bortezomib and bendamustine have both been identified as quickly acting and well-tolerated drugs for patients with MM-induced renal failure. In this retrospective study we analyzed the efficacy of a BPV induction therapy prior ASCT in newly diagnosed MM patients depending on the severity of renal impairment. Methods: Between October 2008 and November 2019, 135 patients with newly diagnosed MM were treated with a BPV-induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 followed by chemomobilization with cyclophosphamide (1-4 g/m2) and ASCT. Results: The majority of patients (n = 117; 87%) responded after the BPV-induction with median of 2 (range 1–6) cycles with 9 sCR (7%), 3 CR (2%), 12 nCR (9%), 39 VGPR (29%), and 54 PR (40%). Stem cell counts of CD 34+ ≥20 × 106/L in the peripheral blood were achieved in 131 (97%) patients after a median of 12 (range 9–17) days. Further four patients with poor stem cell mobilization on day 15 received additional plerixafor. After first ASCT ORR increased to 99% with 33 sCR (24%), 10 CR (7%), 32 nCR (24%), 41 VGPR (30%) and 17 PR (13%). With a median observation time of 51 months, median PFS was 47 months and 60 months OS was 67%. Transplant related mortality was 0.7% (n = 1). Patients were divided into four groups depending on the severity of renal impairment: group A 13 patients with eGFR <15 mL/min, group B 15 patients with eGFR 15–29 mL/min, group C 19 patients with eGFR 30–59 mL/min and group D 88 patients with eGFR ≥60 mL/min. At the time of diagnosis, 8 of 13 patients in group A were dialysis dependent. We observed no significant difference in the median PFS between patients with normal/mild (D), moderate (C), severe renal dysfunction (B) and renal failure/dialysis (A) (50 vs 47 vs 34 vs 24 months, p = 0.053) and in the 60 months OS (69 vs. 72 vs 58 vs. 70%, p = 0.23). In 23 of 38 patients with eGFR ≤50mL/min, we found rapid recovery of renal function during the first two BPV cycles, with four of eight dialysis-dependent patients reverting to independence. BPV induced a rapid reduction in light chain production in the first few days of treatment, potentially preventing the development of irreversible renal failure. Following the ASCT, the renal response rate improved from 61% after BPV induction to 74% with 18 CRrenal (47%), 3 PRrenal (8%) and 7 MRrenal (18%). Conclusions: Our results indicate that the BPV induction followed by high-dose therapy and ASCT is feasible, effective and well tolerated in patients with MM-induced renal failure. Encore Abstract - previously submitted to EBMT 2023 Keywords: Combination Therapies, Multiple Myeloma, Stem Cell Transplant No conflicts of interests pertinent to the abstract. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hon.3165_627

Stem cell mobilization and autologous stem cell transplantation after bendamustine, prednisone and bortezomib induction in multiple myeloma patients with renal impairment

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Stem cell mobilization and autologous stem cell transplantation after bendamustine, prednisone and bortezomib induction in multiple myeloma patients with renal impairment