Allogeneic stem cell transplantation for multiple myeloma: is there a future?

Dhakal, Binod; Vesole, David H.; Hari, Parameswaran

doi:10.1038/bmt.2015.325

Cited by 53 publications

(33 citation statements)

References 98 publications

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“…Phase III data comparing alloSCT after ASCT vs tandem ASCT in the BMT CTN 0102 study found no significant difference in cumulative incidence of disease relapse or progression at 3 years (38 vs 57%, p = 0.079), PFS (p = 0.743) and OS (p = 0.460) amongst patients with high-risk disease treated in these two arms [92]. One of the major limitations for alloSCT is treatment-related toxicity, including graft vs host disease [93] and non-relapse-related mortality [94]. As such, despite the potential benefit for high-risk MM, the IMWG recommends that alloSCT be used only in the setting of clinical trials [3].…”

Section: Stem Cell Transplantationmentioning

confidence: 88%

Current Review on High-Risk Multiple Myeloma

Chan

Chen

Reece

2017

Curr Hematol Malig Rep

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Apart from clinical stage, disease genetics are now recognised as important prognostic risk factors, and various new cytogenetic changes with negative prognostic impact have been identified. New technologies such as minimal residual disease detection are also playing an important role in prognostic assessment. Recent introduction of combination therapy with proteasome inhibitors and immunomodulatory drugs is showing promising results in high-risk patients and may partially abrogate the negative impact associated with some of the adverse risk factors. Recent advance has improved our understanding of high-risk multiple myeloma, and new therapeutic agents are now coming through the pipeline for this patient group with once dismal outcome.

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Section: Stem Cell Transplantationmentioning

confidence: 88%

Current Review on High-Risk Multiple Myeloma

Chan

Chen

Reece

2017

Curr Hematol Malig Rep

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“…9,10 Allogeneic hematopoietic stem cell transplantation and non-CAR autologous T-cell therapies in MM Allogeneic hematopoietic stem cell transplantation has been used to treat MM. 11,12 In studies assessing the efficacy of allogeneic transplant, chronic graft-versus-host disease had a significant protective effect against relapse of MM. 11 A graft-versus-tumor effect from donor lymphocyte infusions yields an overall survival benefit for a subset of relapsed patients.…”

Section: Introductionmentioning

confidence: 99%

“…11 A graft-versus-tumor effect from donor lymphocyte infusions yields an overall survival benefit for a subset of relapsed patients. 12,13 Unfortunately, allogenic transplant and donor lymphocyte infunsions carry high rates of morbidity and mortality, mainly due to graft-versus-host disease, which has prompted investigators to develop autologous T-cell therapies for MM. [11][12][13][14] Noonan et al have used activated marrow-infiltrating lymphocytes (MILs) to target MM.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 Unfortunately, allogenic transplant and donor lymphocyte infunsions carry high rates of morbidity and mortality, mainly due to graft-versus-host disease, which has prompted investigators to develop autologous T-cell therapies for MM. [11][12][13][14] Noonan et al have used activated marrow-infiltrating lymphocytes (MILs) to target MM. 15,16 MILs are a polyclonal population of T cells from the MM bone marrow microenvironment.…”

Section: Introductionmentioning

confidence: 99%

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Chimeric antigen receptor T-cell therapies for multiple myeloma

Mikkilineni¹,

Kochenderfer

2017

Blood

178

176

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Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM. Target antigens for CARs must be expressed on malignant cells, but expression on normal cells must be absent or limited. B-cell maturation antigen is expressed by normal and malignant plasma cells. CAR-Ts targeting B-cell maturation antigen have demonstrated significant antimyeloma activity in early clinical trials. Toxicities in these trials, including cytokine release syndrome, have been similar to toxicities observed in CAR-T trials for leukemia. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-Ts is a novel approach to MM therapy. MM antigens including CD138, CD38, signaling lymphocyte–activating molecule 7, and κ light chain are under investigation as CAR targets. MM is genetically and phenotypically heterogeneous, so targeting of >1 antigen might often be required for effective treatment of MM with CAR-Ts. Integration of CAR-Ts with other myeloma therapies is an important area of future research. CAR-T therapies for MM are at an early stage of development but have great promise to improve MM treatment.

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“…In fact, there are several ongoing prospective studies (clinicaltrials.gov identifiers: 02440464, 020308280, 01460420, 01131169, 02447055) including anti-myeloma drugs as maintenance therapy early after alloSCT that may improve outcomes of MM patients. 42 One study in particular (clinicaltrials.gov identifier: 02440464) will investigate the use of a 2 nd -generation anti-myeloma drug (ixazomib) in association with immunosuppressive therapy after alloSCT.…”

mentioning

confidence: 99%

Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT

Paviglianiti¹,

Xavier²,

Ruggeri³

et al. 2016

Haematologica

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International audienceAlthough allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients

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Allogeneic stem cell transplantation for multiple myeloma: is there a future?

Cited by 53 publications

References 98 publications

Current Review on High-Risk Multiple Myeloma

Current Review on High-Risk Multiple Myeloma

Chimeric antigen receptor T-cell therapies for multiple myeloma

Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT

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