Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)

Roussel, Murielle; Moreau, Philippe; Huynh, Anne; Mary, Jean‐Yves; Danho, Clotaire; Caillot, Denis; Hulin, Cyrille; Fruchart, Christophe; Marit, Gérald; Pégourie, Brigitte; Lenain, Pascal; Araujo, Carla; Kolb, Brigitte; Randriamalala, Edouard; Royer, Bruno; Stoppa, Anne‐Marie; Dib, M.; Dorvaux, Véronique; Garderet, Laurent; Mathiot, Claire; Avet-Loiseau, Hervé; Harousseau, Jean‐Luc; Attal, Michel

doi:10.1182/blood-2009-06-229658

Cited by 160 publications

(116 citation statements)

References 35 publications

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“…Thus, several approaches have been tried to enhance the response to transplantation, but there have been problems with higher morbidity and mortality compared to HDM, which remains the recommended regimen [24][25][26]. Recently, the Intergroupe Francophone du Myelome phase 2 trial showed that conditioning with bortezomib plus melphalan achieved CR or VGPR in almost 70 % of patients with no toxic deaths [13]. Several other groups have subsequently reported similar results [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…This phase 2 study was performed to assess the safety and efficacy of bortezomib and dexamethazone combined with HDM (BD-HDM) as the conditioning regimen. Bortezomib (1 mg/m 2 ) was administered intravenously on days -6, -3, 1, and 4, according to IFM protocol [13]. Dexamethazone (20 mg) was administered orally on days -6, -5, -3, -2, 1, 2, 4, and 5, according to SUMMIT protocol [10].…”

Section: Treatment Protocolmentioning

confidence: 99%

“…Bortezomib is a first-generation proteasome inhibitor that has been proven to be effective for MM [10,11]. Bortezomib has also shown a synergistic effect with melphalan in a clinical trial [12], and some groups have recently reported that combining bortezomib with HDM provides safe and effective conditioning for ASCT [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

Takezako

Sekiguchi

Nagata

et al. 2012

Indian J Hematol Blood Transfus

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Protocolmentioning

confidence: 99%

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Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

Takezako

Sekiguchi

Nagata

et al. 2012

Indian J Hematol Blood Transfus

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“…Prospective trials investigating bortezomib-HDM as the conditioning regimen for a first auto-SCT demonstrated a CR rate of 20-35%, ORR of 85-95% and PFS of 15-18 months, with minimal toxicities. 16,17 Gimsing et al 18 reported a CR rate of 35% and a VGPR rate of 31% in bortezomibnaïve patients undergoing second auto-SCT with bortezomib-HDM conditioning. The PFS was comparable between the first and second auto-SCT in those patients.…”

Section: Introductionmentioning

confidence: 99%

A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma

Fiala

et al. 2014

Bone Marrow Transplant

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High-dose melphalan has been the standard conditioning regimen for auto-SCT in multiple myeloma (MM) for decades. A more effective conditioning regimen may induce deeper responses and longer remission duration. It is especially needed in the setting of second auto-SCT, which rarely achieves comparable results with the first auto-SCT using the same conditioning regimen. Here we conducted a phase II study to investigate the efficacy and safety of a conditioning regimen V-BEAM (bortezomib-BEAM) before second auto-SCT for multiple myeloma. Ten patients were enrolled from September 2012 to May 2013. The CR rate at day +100 after auto-SCT was 75%; all except for one patient remained in remission after a median follow-up of 6 months. Three patients developed Clostridium difficile infection. Two patients died within the first 30 days of auto-SCT from neutropenic colitis and overwhelming sepsis, respectively. Due to the high rate of morbidity and mortality, the study was terminated after 10 patients. In summary, although the conditioning regimen V-BEAM before second auto-SCT for MM provided promising responses, it was associated with unexpected treatment-related toxicity and should not be investigated further without modifications. INTRODUCTIONMultiple myeloma (MM) is the second most common hematological malignancy in the United States, accounting for more than 22 000 new cases and over 10 500 deaths in 2013. 1 Treatment with high-dose chemotherapy and auto-SCT results in improved overall response rates (ORRs), CR rates, PFS and OS compared with treatment with standard dose chemotherapy. 2 Recent studies have shown that lenalidomide maintenance therapy after auto-SCT further prolongs PFS. 3,4 Despite the benefits of auto-SCT and lenalidomide maintenance, MM remains incurable, with the median PFS after auto-SCT of 41-46 months. 3,4 For patients who relapse after auto-SCT, a second auto-SCT could be considered for salvage therapy. Several retrospective studies have demonstrated that the median PFS after a second auto-SCT is reduced by at least 50% when compared with that of the first auto-SCT. 5-9 Therefore, salvage auto-SCT provides more benefit to patients who maintain a remission for more than 2 years after the first auto-SCT, 10,11 and in practice, is often reserved only for such patients.High-dose melphalan (HDM, 200 mg/m 2 ) has remained the standard auto-SCT conditioning regimen in MM for more than 10 years 12 as no other conditioning regimens have shown superiority over HDM because of additive toxicities. [13][14][15] In patients who relapse after a first auto-SCT with HDM, a different conditioning regimen may overcome resistance to melphalan, resulting in improved ORR, PFS and OS. With a more effective conditioning regimen, a second auto-SCT may benefit more patients, including those with a short PFS after the first auto-SCT.Bortezomib is effective in treating patients with newly diagnosed or refractory/relapsed MM. Recently, several clinical

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“…In phase I/II studies, combining bortezomib with HD melphalan has shown improved depth of response irrespective of induction therapy. 10,11 A phase I/II dose-escalation study of lenalidomide augmenting high dose melphalan (HDM) is currently under recruitment. The results presented in this issue of Bone Marrow Transplantation provide further evidence of the utility of combinational conditioning regimens utilizing novel agents.…”

mentioning

confidence: 99%

Re-invigorating rather than re-inventing the wheel: augmenting the impact of salvage autologous stem cell transplantation for multiple myeloma in the era of novel agents

Cook

2015

Bone Marrow Transplant

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-3369/15 www.nature.com/bmt patient stratification and the use of currently evolving technology to delineate key biomarkers of response prediction. This is an area that has yet to be defined in relation to salvage ASCT.Although salvage ASCT has been utilized in clinical practice for relapsed myeloma after a prior ASCT for many years, it is only in recent times that prospective studies have demonstrated the utility of this compared with a no-transplant strategy, as well as the evolution of investigational-conditioning regimens. The direction of travel is clearly to establish as good a durable response to the second ASCT as to the first ASCT, such that there can be an expected improvement in the overall survivorship. More studies are planned in this setting, which is to be welcomed. CONFLICT OF INTERESTGC has received honoraria, research funding and speakers bureau fees from Janssen, Celgene, Amgen and Takeda Millennium.G Cook

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Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)

Cited by 160 publications

References 35 publications

Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma

Re-invigorating rather than re-inventing the wheel: augmenting the impact of salvage autologous stem cell transplantation for multiple myeloma in the era of novel agents

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