Introduction: Autologous stem cell transplantation (ASCT) is the standard first line treatment for younger patients with multiple myeloma (MM). Bortezomib and bendamustine have both been identified as rapidly acting and well-tolerated drugs for patients with MM-induced renal failure. In this retrospective study we analyzed the efficacy of induction therapy with a combination bendamustine, prednisone and bortezomib (BPV) prior to ASCT in newly diagnosed MM-patients (NDMM) depending on severity of renal impairment. Methods 135 patients with NDMM were treated with BPV-induction. Results The majority of patients (n = 117; 87%) responded after BPV-induction with 9 sCR, 3 CR, 12 nCR, 39 VGPR, and 54 PR. After first ASCT ORR increased to 99% with 33 sCR, 10 CR, 32 nCR, 41 VGPR and 17 PR. Median PFS was 47 months and OS at 60 months was 67%. Patients were divided into four groups depending on severity of renal impairment: A (n = 13) with eGFR < 15mL/min, B (n = 15) 15–29mL/min, C (n = 19) 30-59mL/min and D (n = 88) ≥ 60mL/min. We observed no significant difference in PFS between patients with normal/mild, moderate, severe renal dysfunction and renal failure/dialysis (50 vs 47 vs 34 vs 24 months, p = 0.05) and in 60 months OS (69 vs 72 vs 58 vs 70%, p = 0.23). The renal response rate improved from 61% after BPV to 74% following ASCT. Conclusions These results indicate that BPV-induction followed by ASCT is feasible, effective and well tolerated in patients with MM-induced renal failure. Furthermore, we showed that pretreatment with short-term bendamustine had no negative impact on stem cell mobilization.

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the consolidation therapy with the highest chance of sustained remission for most patients (pts) with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse occurs in up to 40% of pts and adversely affects prognosis. Currently, post-HSCT relapse strategies include intensive chemotherapy, hypomethylating agents (HMA), as well as targeted therapy, e.g. FLT3-inhibitors frequently combined with donor lymphocyte infusions (DLIs). Here we investigated combinations of HMA and venetoclax (VEN) as salvage options for relapse after alloHSCT. Methods: 2 MDS and 24 AML pts (median age 60 [range 38-73] years) relapsed after a median of 6.2 (range 1.6-55.5) months (mo) after 1st (n=22) or 2nd (n=4) HSCT. Conditioning regimens were myeloablative (n=5) or non-myeloablative (n=21). Remission status at HSCT was composite complete remission (CRc; including CR, CR with incomplete recovery [CRi] and morphologic leukemia free state [MLFS]; 50%), partial remission or stable disease (12%), and refractory (38%). While 22 pts had hematological relapse, 4 pts showed either combined (n=3) or sole (n=1) extramedullary disease. All pts subsequently received HMA/VEN-based therapies (azacitidine/venetoclax [n=22], azacitidne/venetoclax/gilteritinib [n=3] or decitabine/venetoclax [n=1]) with concomitant DLI in 13 pts. Prior to HMA/VEN, 13 pts received a different relapse therapy including azacitidine [n=7], gilteritinib [n=2], radiation [n=1], an investigational therapy with an IRAK4 inhibitor [n=1], or a combination therapy with azacitidine and pevonedistat [n=1] or tagraxofusp [n=1]. European LeukemiaNET 2022 risk at the timepoint of relapse was favorable (n=2), intermediate (n=4) or adverse (n=20). Median follow-up since HMA/VEN start was 6.4 mo. Results: HMA/VEN was well tolerated and administered in an outpatient setting in 20/26 pts (77%). The most common adverse effects were expected and included neutropenia CTCAE 3/4° in 25/26 pts (96%) and thrombocytopenia CTCAE 3/4° in 22/26 pts (85%). Eight pts (31%) developed at least one episode of febrile neutropenia. Four pts (15%) showed signs of afebrile infections and were hospitalized. Thirteen pts (50%) achieved a CRc (CR [n=3], CRi [n=8], MLFS [n=2]) under HMA/VEN therapy (Figure 1A), with a median time to 1st and best morphological response of 1.0 and 2.1 mo, respectively. Later relapse (>12 mo after HSCT) and a lower number of prior therapies before HMA/VEN (≤2 vs. >2 lines) associated with improved outcomes (cumulative incidence of achieving a CRc: P=.004 and P=.04, and OS: P=.02 and P=.02, respectively). Six of 13 pts (46%), who received a prior non-HMA/VEN therapy for the current relapse achieved a CRc after switching to HMA/VEN. Pts achieving a CRc had a significantly longer OS compared to pts with no CRc (P=.002; Figure 1B). Of the pts with CRc, 7 continued HMA/VEN with a median response duration of 7.2 mo (6/7 pts are still on treatment at last follow-up), 5 received a 2nd HSCT and 1 an experimental CART-therapy. For those that could be bridged to a 2nd HSCT outcomes were beneficial with 4/5 pts (80%) alive and disease-free (median follow-up since 2nd HSCT: 4.3 months). One patient with CART-therapy suffered from a 2nd relapse 1.7 months after treatment and is currently again salvaged with HMA/VEN. Two of 13 pts (15%) died after initial CRc, 1 due to non-relapse mortality of a 2nd HSCT and 1 by losing treatment response. Of the 13 pts who did not achieve a CRc, 1 patient could be bridged to 2nd HSCT with a post-HSCT relapse free survival of 12 mo. In the remaining 12 non-CRc pts median OS since start of HMA/VEN was 2.9 mo (range 0.7-6.5 mo) and 9/12 pts (75%) died due to progressive disease. Regarding the molecular risk profile, none of the TP53 mutated pts (n=3) responded, whereas pts with IDH1/2, NPM1, or myelodysplasia-related gene mutations, i.e.ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, or ZRSR2, had mixed responses (2/5 pts [40%], 1/3 pts [33%], and 8/15 pts [53%], respectively). Conclusion: HMA/VEN is a promising and well tolerated treatment strategy for MDS and AML pts relapsing after HSCT with a CRc of 50% and potential long-term survival. Especially pts that could be bridged to a 2nd HSCT benefited from the treatment. However, in pts with a disease resistant to HMA/VEN, outcome was very poor with a median OS of only 2.9 mo. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Introduction Light chain involvement is observed in almost every patient (pt) with newly diagnosed multiple myeloma (MM). Owing to a relatively short half-life, rapid reduction in the involved free light chain (iFLC) is of potential prognostic value. Methods This retrospective analysis included 92 pts with newly diagnosed MM treated with bendamustine, prednisone, and bortezomib (BPV). Results After a median number of two (range 1–5) BPV cycles, the majority of pts ( n = 86; 93%) responded with either sCR ( n = 21), CR ( n = 1), nCR ( n = 25), VGPR ( n = 20), or PR ( n = 19). PFS and OS at 48 months were 39% and 67%, respectively. At baseline, 79 out of 92 pts (86%) had iFLC levels above the upper standard level and an abnormal ratio of involved to uninvolved free light chain ≥ 8. In a subgroup analysis of these pts, we evaluated the prognostic importance of an early reduction of the iFLC during the first two BPV cycles. A reduction ≥ 50% of the iFLC on day 8 of the first cycle was observed in 31 of 69 pts. These pts had a significantly better median PFS of 49 months as compared to 20 months in 38 pts with a lower iFLC reduction ( p = 0.002). In contrast, OS did not differ significantly with a 48 months survival of 77% vs 69% ( p > 0.05). Conclusion These results indicate that a rapid decrease in the iFLC on day 8 is an early prognostic marker for newly diagnosed MM pts undergoing BPV treatment.

Reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing.

Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing.

Bortezomib is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination in patients with multiple myeloma (MM). In the present protocol, bortezomib was combined with bendamustine and prednisone, in order to assess the efficacy and safety of this combination therapy in patients with newly diagnosed/untreated MM.

PURPOSE:Renal failure is a frequent complication of multiple myeloma (MM) and, if present at diagnosis, a considerable risk factor for outcome. Treatment with chemotherapy and/or new agents may result in recovery of renal function in up to 50 % of patients. The window of opportunity to reverse renal impairment is, however, rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as bendamustine has been demonstrated to be potent drugs in the treatment of MM. METHODS:A total of 18 patients with newly diagnosed/untreated MM and renal insufficiency (GFR < 35 ml/min) were treated with bendamustine, prednisone, and bortezomib (BPV). RESULTS:The majority of them (n = 15; 83 %) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow-up of 17 months, PFS at 18 months was 57 % and OS was 61 %. The myeloma protein decreased rapidly, reaching the best response after the first cycle in four and after the second cycle in additional seven patients. Thirteen patients (72 %) improved their renal function after treatment. CONCLUSION:We conclude that the combination of bortezomib, bendamustine, and prednisone is effective and well tolerated in patients with a newly diagnosed MM and renal failure.