Bendamustine-based conditioning for non-Hodgkin lymphoma autologous transplantation: an increasing risk of renal toxicity

Garciaz, Sylvain; Coso, Diane; Collela, J; Broussais, Florence; Am, Stoppa; Aurran, Thérèse; Chabannon, Christian; Helvig, A.; Xerri, Luc; Blaise, Didier; Bouabdallah, Réda

doi:10.1038/bmt.2015.257

Cited by 34 publications

(50 citation statements)

References 15 publications

(17 reference statements)

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“…[44][45][46][47][48] Recently, a single-center, retrospective study in 29 R/R patients (DLBCL, n ¼ 18; mantle cell lymphoma, n ¼ 11) followed at the PaoliCalmettes Cancer Center in France, reported that patients given Benda-EAM were admitted to the intensive care unit (ICU) more frequently than a historic, matched cohort treated with conventional BEAM (24% versus 11%, respectively; p ¼ 0.07). [17] In addition, rates of Grade 3 renal and cardiac toxicity were significantly greater in patients given Benda-EAM than those given BEAM (renal toxicity, p < 0.001; cardiac toxicity, p ¼ 0.02). However, there are a number of limitations of the later study that do not allow for adequate interpretation of the safety data.…”

Section: Benda-eammentioning

confidence: 96%

“…[15] Standard BEAM consists of carmustine (300 mg/m 2 x1, day -6), etoposide (200 mg/m 2 , days -5 to -2), cytarabine (200 mg/m 2 b.i.d., days -5 to -2), and melphalan (140 mg/kg/day Â1, days -1). [16,17] Studies using BEAM in R/R NHL and HL have demonstrated three-and five-year PFS rates of 39% to 81% and 35% to 69%, respectively. [12,13,15,[18][19][20][21][22][23][24][25][26][27][28][29][30] (Table 1) Long-term OS rates have ranged from 59% to 88% at three years and from 41% to 81% at five years.…”

Section: The Beam Regimenmentioning

confidence: 98%

“…[15] Unfortunately, carmustine is often not reimbursed or is prohibitively expensive. [17] Therefore, BEAM and other carmustine-containing regimens are not an option for all treating physicians; alternative regimens are therefore needed and used by many institutions.…”

Section: Introductionmentioning

confidence: 99%

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Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Isidori¹,

Christofides

Visani³

2016

Leukemia & Lymphoma

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High-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Until recently, carmustine, etoposide, cytarabine and melphalan (BEAM) was the most commonly used conditioning regimen in this setting, given its acceptable efficacy and tolerability. Despite reasonable success with BEAM, carmustine is associated with a number of acute and late toxicities. Moreover, recent supply and cost issues for this agent have created an urgent need for alternative conditioning regimens. As such, etoposide and melphalan (VP16/MEL) or busulfan, cyclophosphamide, and etoposide (BuCyE) are currently being used with limited success. A number of novel conditioning regimens that replace carmustine with other agents are under investigation, which may provide effective alternatives to BEAM. In considering novel agents to replace carmustine, bendamustine may provide the best alternative, as demonstrated by the results of a number of phase II, multicenter, controlled studies.

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Section: Benda-eammentioning

confidence: 96%

Section: The Beam Regimenmentioning

confidence: 98%

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Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Isidori¹,

Christofides

Visani³

2016

Leukemia & Lymphoma

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“…Atrial fibrillation was reported in 10 and 8% of patients in the studies by Garciaz and Noesslinger et al, 41,44 , respectively. Need for ICU management was reported in 28% of patients in the study by Garciaz et al 44 3-Year PFS and OD were 72% in the study by Visani et al b Resolved in all cases (in Martin, three patients already had a kidney failure episode).…”

mentioning

confidence: 98%

“…39,40 Several reports on the use of a bendamustine-based conditioning regimen before auto-HSCT were recently published as abstracts (Table 2 and Supplementary Table 2) 41-43 and a journal letter. 44 Bendamustine was used at 200 mg/m 2 /day for two successive days in these studies, except for the study reported by Martino et al, 42 in which bendamustine was used at a dose of 100 mg/m 2 in combination with melphalan for patients with multiple myeloma. Toxicities were comparable between the different studies ( Table 2).…”

mentioning

confidence: 99%

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review

Damaj

Cornillon

Bouabdallah

et al. 2017

Bone Marrow Transplant

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High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.

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Bendamustine‐based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers

Chantepie¹,

Garciaz

Tchernonog

et al. 2018

American J Hematol

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Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.

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Bendamustine-based conditioning for non-Hodgkin lymphoma autologous transplantation: an increasing risk of renal toxicity

Cited by 34 publications

References 15 publications

Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review

Bendamustine‐based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers

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