Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation

Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m 2 (Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) o 60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ⩾ 60 mL/min (median 83 mL/min, range 60-128). Patients with CrCl o60 mL/min had longer time to neutrophil (P = 0.008) and platelet engraftment (P o 0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl o 60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl o60 mL/min group and 47 months (range 1-45) in the CrCl ⩾ 60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P = 0.0025). Multivariate analysis showed CrCl o 60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min.

Section: Baseline Characteristicsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

Sweiss

Patel

Culos

et al. 2016

“…Nowadays, there is no consensus regarding the best conditioning regimen. 3,14 HDM at a dose of 200 mg/m 2 is considered to be the standard conditioning regimen. 14,17,18,30 However, a variety of strategies has been explored with the aim of improving the results of HDM 200 mg/m 2 , including dose escalation, 22 addition of other agents such as busulfan, thiotepa or TBI 14,15,[17][18][19][20][21][22] or, conversely, dose reduction as part of a tandem auto-SCT procedure, 20 with overall mixed results.…”

Section: Discussionmentioning

confidence: 99%

“…2 For almost 25 years, therapeutic intensification with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) has been considered as the standard of care in MM patients without significant comorbidities. 2,3 Although this approach is currently being debated by some investigators in the modern therapy era, 4 it still represents the standard treatment strategy; 5 and the incorporation of novel agents into different phases of the transplant procedure, including induction, [6][7][8][9] consolidation, 10,11 and maintenance 12,13 has substantially improved outcomes.…”

Section: Introductionmentioning

confidence: 99%

A phase II, single-arm, prospective study of bendamustine plus melphalan conditioning for second autologous stem cell transplantation in de novo multiple myeloma patients through a tandem transplant strategy

Martino

Tripepi

Messina

et al. 2016

This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m 2 ) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m 2 ) and HDM (140 mg/m 2 ). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P = 0.025 and 78.1 vs 100%, P = 0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P = 0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.

“…3,4 High-dose melphalan (HDM) at 200 mg/m 2 is the standard conditioning for ASCT 5,6 and, today, the treatment should be considered a safe procedure with a very low transplant-related mortality (TRM). [7][8][9] The significant increase in the waiting lists generated concerns about the appropriate use of health care resources and, over the past years, some studies have investigated the safety, efficacy and potential cost advantages of reducing hospital stay for patients undergoing ASCT.…”

Section: Introductionmentioning

confidence: 99%

Italian consensus conference for the outpatient autologous stem cell transplantation management in multiple myeloma

Martino¹,

Lemoli

Girmenia

et al. 2016

Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital stay for MM patients undergoing ASCT have been widely explored, and different outpatient models have been proposed. However, there is no agreement on the criteria for selecting patients eligible for this strategy as well as the standards for their clinical management. On the basis of this rationale, the Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop guidelines for the management of outpatient ASCT in MM, using evidence-based knowledge and consensus-formation techniques. An expert panel convened to discuss the currently available data on the practice of outpatient ASCT management and formulated recommendations according to the supporting evidence. Evidence gaps were filled with consensus-based statements. Three main topics were addressed: (1) the identification of criteria for selecting MM patients eligible for outpatient ASCT management; (2) the definition of standard procedures for performing outpatient ASCT (model, supportive care and monitoring during the aplastic phase); (3) the definition of the standard criteria and procedures for re-hospitalization during the aplastic phase at home. Herein, we report the summary and the results of the discussion and the consensus. INTRODUCTIONMultiple myeloma (MM) remains the leading indication for highdose chemotherapy and autologous stem cell transplantation (ASCT) worldwide 1,2 and the International Guidelines recommend that ASCT should be offered at some point during the treatment program for a medically fit patient. 3,4 High-dose melphalan (HDM) at 200 mg/m 2 is the standard conditioning for ASCT 5,6 and, today, the treatment should be considered a safe procedure with a very low transplant-related mortality (TRM). 7-9 The significant increase in the waiting lists generated concerns about the appropriate use of health care resources and, over the past years, some studies have investigated the safety, efficacy and potential cost advantages of reducing hospital stay for patients undergoing ASCT. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] The ease of administering HDM, the relatively low extra-hematological toxicity and the short period of neutropenia 5,6 make MM patients ideal candidates for outpatient ASCT programs. Standardization of criteria for the outpatient ASCT policy is a relevant goal of the Italian hematology and transplant community and may facilitate comparison of retrospective and prospective data. The Italian Group for Stem Cell Transplantation (GITMO) endorsed a panel of 10 experts in the transplant field (MMa, RML, CG, LC, BB, MO, IL, MMo, GM and AO) to propose a consensus for the selection criteria and management of MM patients for ASCT procedure in the outpatient setting. METHODSA working group of 10 experts from 7 GITMO centers, with specific expertise in the field of ASCT, convened four times to: (a) identify common criteria for selecti...