P-170: Stem cell mobilization and autologous stem cell transplantation after induction with bendamustine, prednisone and bortezomib (BPV) in 135 untreated myeloma patients with variable renal function

Introduction: Autologous stem cell transplantation (ASCT) is the standard first line treatment for younger patients (pts) ( < 70 years) with multiple myeloma (MM). Approximately 20-50 % of all pts already display an impaired kidney function at diagnosis. However, most of MM pts with severe renal dysfunction are excluded from ASCT studies. Bortezomib and bendamustine have both been identified as quickly acting and well-tolerated drugs for pts with MM-induced renal failure. In this retrospective study we analyzed the efficacy of a BPV induction therapy prior ASCT in newly diagnosed MM pts depending on the severity of renal impairment. Furthermore, additional information is needed on stem cell toxicity of BPV-induction using chemomobilization.

Methods: Between October 2008 and November 2019, 135 pts with newly diagnosed MM were treated with BPV-induction consisting of bendamustine 60mg/m2 on days 1 and 2, bortezomib 1.3mg/m2 on days 1, 4, 8 and 11 and prednisone 100mg on days 1, 2, 4, 8 and 11. PBSC collection was performed 2-3 weeks after BPV induction.

Results: The majority of pts (n=117; 87%) responded after median 2 (range 1-6) BPV-cycles with 9 sCR, 3 CR, 12 nCR, 39 VGPR and 54 PR. For stem cell mobilization, 111 pts received cyclophosphamide 4g/m2 and 24 pts with severe renal failure or pre-existing heart disease 1-2g/m2. Stem cell counts of CD34+≥20x106/L in the peripheral blood were achieved in 131 (97%) pts after a median of 12 (range 9-17) days. Further four pts (3%) with poor stem cell mobilization on day 15 received additional plerixafor. In 96 of 135 pts (71%) a single apheresis was sufficient to reach the target of 8x106 CD34+/kg. Transplant related mortality was 0.7%. Engraftment was successful in 134 of 135 pts. After first ASCT ORR increased to 99% with 33 sCR, 10 CR, 32 nCR, 41 VGPR and 17 PR. With a median observation time of 51 months, median PFS was 47 months and 60 months OS was 67%. Pts were divided into four groups depending on the severity of renal impairment: group A 13 pts with eGFR < 15mL/min, group B 15 pts with eGFR 15-29mL/min, group C 19 pts with eGFR 30-59mL/min and group D 88 pts with eGFR ≥60mL/min. At the time of diagnosis, 8 out of 13 pts in group A were dialysis dependent. We observed no significant difference in the median PFS between pts with normal/mild, moderate, severe renal dysfunction and renal failure/dialysis (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). 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%). Four of the eight dialysis-dependent pts became dialysis-independent.

Conclusions: BPV is a highly effective and well-tolerated induction-treatment protocol prior to ASCT in patients with MM-induced renal failure. Pretreatment with two cycles of BPV has no negative influence on stem cell mobilization and hematopoietic recovery after ASCT.