Bortezomib, Bendamustine and Dexamethasone vs Thalidomide, Bendamustine and Dexamethasone in Myeloma patients presenting with renal failure (OPTIMAL): a randomised, multi-centre phase II trial

Ramasamy, Karthik; Iqbal, Gulnaz; Brouwer, Richard; Stalker, Victoria; Akhtar, Salma; Varghese, Sherin; Lindsay, Jindriska; Schey, Stephen; Drayson, Mark T.; Dunn, Janet A.

doi:10.1038/s41408-022-00758-7

Cited by 3 publications

(3 citation statements)

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“…Partly due to premature closure of the trial, which itself is an expression of the challenges recruiting this population, especially after approval and wide availability of the triplet regimen, the patient number was limited. The challenge to recruit patients with severe RI into clinical trials was recently also documented by Ramasamy et al who reported 57 screen failures out of 88 screened patients for their OPTIMAL trial for newly diagnosed MM patients presenting with renal failure [ 24 ]. In OPTIMAL, most screen failure were due to frailty of the patients [ 24 ], again highlighting the special need of this specific population, and possibly contributing to the lack of attractiveness to include these patients into clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…The challenge to recruit patients with severe RI into clinical trials was recently also documented by Ramasamy et al who reported 57 screen failures out of 88 screened patients for their OPTIMAL trial for newly diagnosed MM patients presenting with renal failure [ 24 ]. In OPTIMAL, most screen failure were due to frailty of the patients [ 24 ], again highlighting the special need of this specific population, and possibly contributing to the lack of attractiveness to include these patients into clinical trials. In addition, at the time of the conception of the GMMG-DANTE trial, assessments of minimal residual disease (MRD) were not yet widely available, so data on MRD negativity could not be collected.…”

Section: Discussionmentioning

confidence: 99%

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Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial

Leypoldt,

Gavriatopoulou,

Besemer

et al. 2023

Cancers

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Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR <30 mL/min/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial

Leypoldt,

Gavriatopoulou,

Besemer

et al. 2023

Cancers

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“…Previous studies with small numbers of patients suggest that treatment with new substances and/or conventional chemotherapy results in recovery of renal function in more than 50% of the cases (Dimopoulos et al 2009;Roussou et al 2010;Dimopoulos et al 2016). An example of the use of the new drugs is the combination of bortezomib with bendamustine and corticosteroids, which has been assessed in several studies in the rst line setting (Pönisch et al 2014;Mateos et al 2015;Berdeja et al 2017;Ramasamy et al 2022). The combination of bendamustine, prednisone and bortezomib (Velcade®) (BPV) was particularly effective in 18 MM patients with severe renal insu ciency with a hematological overall response rate (ORR) of 83% and an improvement of renal function in 72% (Pönisch et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Bendamustine, prednisone and bortezomib (BPV) induction therapy prior autologous stem cell transplantation (ASCT) in 135 newly diagnosed multiple myeloma patients: comparison between patients with normal and impaired renal function

Fricke,

Wang,

Holzhey

et al. 2023

Preprint

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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.

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Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group

Dimopoulos

Merlini

Bridoux

et al. 2023

The Lancet Oncology

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Bortezomib, Bendamustine and Dexamethasone vs Thalidomide, Bendamustine and Dexamethasone in Myeloma patients presenting with renal failure (OPTIMAL): a randomised, multi-centre phase II trial

Cited by 3 publications

References 16 publications

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial

Bendamustine, prednisone and bortezomib (BPV) induction therapy prior autologous stem cell transplantation (ASCT) in 135 newly diagnosed multiple myeloma patients: comparison between patients with normal and impaired renal function

Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group

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