Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial

Bashir, Qaiser; Thall, Peter F.; Milton, Denái R.; Fox, Patricia S.; Kawedia, Jitesh D.; Kebriaei, Partow; Shah, Nina; Patel, Krina; Andersson, Börje S.; Nieto, Yago; Valdez, Ben C.; Parmar, Simrit; Rondón, Gabriela; Delgado, Ruby; Hosing, Chitra; Popat, Uday; Oran, Betül; Ciurea, Stefan O.; Lin, Pei; Weber, Donna M.; Thomas, Sheeba K.; Lee, Hans C.; Manasanch, Elisabet E.; Orłowski, Robert Z.; Williams, Loretta A.; Champlin, Richard E.; Qazilbash, Muzaffar H.

doi:10.1016/s2352-3026(19)30023-7

Cited by 81 publications

(69 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, it has been used for myeloablative-conditioning regimens before stem cell transplantation. 12,13,23 Busulfan was used to produce the small intestine mucositis animal model in current investigation because it causes mucositis in patients. [12][13][14] Many investigations have attempted to reduce chemotherapy-induced intestinal disruption by using prebiotics, probiotics, selenium, volatile oils, and others, 1,2,24,25 however, these efforts have not been successful.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis

et al. 2020

View full text Add to dashboard Cite

Worldwide the incidence of cancer has been continuing increasing. Mucositis of the gastrointestinal tract is a common side effect in patients under chemotherapy. Anticancer drug busulfan, used for treating chronic myeloid leukemia especially in pediatric patients, causes mucositis of the gastrointestinal tract. Alginate oligosaccharides (AOS) are natural products with attractive pharmaceutical potentials. We aimed to investigate, at the single-cell level, AOS preventing small intestine mucositis induced by busulfan. We found that busulfan disturbed the endoplasmic reticulum and mitochondria of cells in the small intestine, damaged cell membranes especially cell junctions, and disrupted microvilli; all of which were rescued by AOS. Single-cell RNA sequencing analysis and functional enrichment analysis showed that AOS could recover small intestinal function. Deep analysis found that AOS improved the expression of transcriptional factors which explained AOS regulating gene expression to improve small intestine function. Further investigation in IPEC-J2 cells found that AOS acts its function through mannose receptor signaling pathway. Moreover, the improved blood metabolome confirmed small intestinal function was recovered by AOS. As a natural product with many advantages, AOS could be developed to assist in the recovery of intestinal functions in patients undergoing anticancer chemotherapy or other treatments.

show abstract

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Qazilbash et al reported results of a phase 3 study comparing Bu-Mel versus melphalan alone in NDMM patients. 8 The Bu-Mel group had significantly longer PFS than melphalan alone even in patients with high-risk cytogenetics (median PFS 64.7 vs 43.5 months, P = .022 and not reached (NR) versus 25 months, P = .0087 in all patients and highrisk cytogenetics patients, respectively). Importantly, intravenous busulfan did not increase the risk of sinusoidal obstructive syndrome (SOS).…”

Section: High Dose Melphalan: Are There Any Alternatives To Improvementioning

confidence: 86%

Expert perspective: Highlights on myeloma cell therapy from the American Society of Hematology Annual Meeting 2019

Kunacheewa

Manasanch

2020

Adv. Cell Gene Ther.

View full text Add to dashboard Cite

The use of high dose melphalan with stem cell rescue (ASCT) has been part of the standard of care for myeloma (MM) patients since the 1990s. Recent data from the European Group for Blood and Marrow Transplantation (EBMT) were presented, which included 103 032 patients from 54 countries from 1993 to 2017. This showed an increasing number of patients receiving ASCT and longer progression-free survival (PFS) and overall survival (OS) overtime along with increased use of novel agents and triple-therapy initially. 1 Fortunately, nine agents have been approved for the treatment of MM by regulatory agencies from 2003 to 2019 with resulting improvement in clinical outcomes. Despite this improvement, the majority of MM patients continue to relapse. New cell therapy options, including chimeric antigen receptor (CAR)-T-cell therapies, are being explored in heavily pretreated and high-risk/early relapse patients. 2 In this commentary, we highlight studies presented at the American Society of Hematology (ASH) Annual Meeting held in Orlando, FL in December 2019. 2 | HI G H DOS E MELPHAL AN AND S TEM CELL RE SCUE IN MYELOMA 2.1 | Does ASCT remain relevant in the treatment of multiple myeloma? Upfront ASCT has been associated in a phase III study with deep response, MRD negativity and longer PFS when compared to delayed ASCT. Despite this, OS has been similar in upfront vs delayed transplant using novel agents as initial therapy. 3 The FORTE study in newly diagnosed myeloma (NDMM) compared four cycles of carfilzomib/lenalidomide/dexamethasone (KRd) followed by ASCT versus 12 cycles of KRd without ASCT both showing similar rates of MRD negativity. Despite similar MRD negativity, patients that received ASCT relapsed less compared to patients without ASCT, particularly in patients with Revised International Staging System (R-ISS) II/III. 4 Another study of 124 NDMM patients (93 had upfront and 31 delayed ASCT) showed similarly that upfront ASCT provided significantly better PFS1 (from diagnosis to 1st relapse, PFS1 = 6.45 vs 1.25 years, P < .001) and PFS2 (from diagnosis to 2nd relapse, PFS2 = 9.19 vs 3.69 years, P < .001). 5 2.2 | What are the factors that may predict early relapse after ASCT? Disease relapse is an obstacle to long-term survival in MM patients. The analysis of 474 NDMM patients from the FORTE study identified three factors that can predict early disease relapse at 18 months. These factors include: R-ISS II/III (particularly those patients with high LDH level), presence of circulating plasma cells and MRD status prior to ASCT. 6 The Center for International Blood and Marrow Transplant Research (CIBMTR) has generated a model to predict relapsed disease in patients treated with upfront ASCT. 7 The model included cytogenetic risk, initial therapy, bone marrow plasma cell infiltration prior to ASCT and number

show abstract

“…Furthermore, the addition of bortezomib to the high dose melphalan conditioning regimen did not improve outcomes [76]. However, a recent phase 3 clinical trial evaluating the addition of busulfan in the conditioning setting showed that busulfan followed by melphalan at 140 mg/m 2 resulted in a prolonged PFS of 64.7 months compared with 43.5 months with melphalan at 200 mg/m 2 alone (p = 0.022) [77]. Therefore, this combination regimen may become the new standard of care in the near future.…”

Section: Mobilization and Conditioning Regimensmentioning

confidence: 99%

Multiple myeloma: Role of autologous transplantation

Ntanasis‐Stathopoulos¹,

Gavriatopoulou²,

Kastritis

et al. 2020

Cancer Treatment Reviews

View full text Add to dashboard Cite

Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial

Cited by 81 publications

References 29 publications

Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis

Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis

Expert perspective: Highlights on myeloma cell therapy from the American Society of Hematology Annual Meeting 2019

Multiple myeloma: Role of autologous transplantation

Contact Info

Product

Resources

About