Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Ahmad, Imran; LeBlanc, Richard; Cohen, Sandra; Lachance, Silvy; Kiss, Thomas; Sauvageau, Guy; Dc, Roy; Busque, Lambert; Delisle, Jean-Sébastien; Bambace, Nadia M.; Bernard, Léa; Sabry, Waleed; Roy, Jean-Philippe

doi:10.1038/bmt.2015.319

Cited by 13 publications

(17 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the trials involved in our meta-analysis, 55 [ 10 – 15 , 17 , 19 – 25 , 27 – 36 , 38 – 52 , 57 – 65 , 67 – 73 ] trials reported grades 2–4 acute GVHD (aGVHD) with the incidence varying from 2.3 to 69.6%, 38 trials [ 10 , 11 , 13 , 14 , 21 , 23 , 25 , 27 – 30 , 32 – 34 , 36 , 38 , 40 – 42 , 44 , 45 , 47 – 50 , 52 , 58 , 59 , 61 , 63 – 65 , 67 – 70 , 72 , 74 ] reported extensive chronic GVHD (cGVHD) with the incidence ranging from 5.3 to 79.3%, and 30 trials [ 11 , 13 , 22 , 23 , 25 , 27 – 34 , 36 – 38 , 40 , 42 , 44 , 45 , 48 – 50 , 58 , 59 , 63 , 64 , 68 , 69 , 72 ] reported limited cGVHD with the incidence varying from 5.1 to 46.3%. There were significant heterogeneity in the pooled estimates of the incidence of aGVHD (p = 0, I 2 = ...…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Yin¹,

Tang²,

Fan³

et al. 2018

Cancer Cell Int

View full text Add to dashboard Cite

BackgroundDespite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT.Patients/methodsWe systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords ‘allogeneic’ and ‘myeloma’.ResultsA total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56–84%), 62 (95% CI 53–71%), 52 (95% CI 44–61%), and 46 (95% CI 40–52%), respectively; for progression-free survival were 51 (95% CI 38–64%), 40 (95% CI 32–48%), 34 (95% CI 27–41%), and 27 (95% CI 23–31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14–21%), 21 (95% CI 17–25%), 20 (95% CI 13–26%), and 27 (95% CI 21–33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5–18%). The incidences of grades II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30–37%) and 51 (95% CI 46–56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45–55%) and 51 (95% CI 45–57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk.ConclusionDue to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0553-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

“…37 [ 10 – 13 , 15 , 19 , 20 , 22 , 24 , 26 – 28 , 31 – 33 , 36 , 38 , 40 , 42 – 45 , 47 – 50 , 57 – 60 , 64 – 67 , 69 , 72 , 73 ] out of 61 trials reported the results of RR with the incidence ranging from 14.3 to 91.3%. The pooled estimate (95% CI) for RR was 50 (95% CI 45–55%).…”

Section: Resultsmentioning

confidence: 99%

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Yin¹,

Tang²,

Fan³

et al. 2018

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…We and others reported a promising post transplantation strategy using pre-emptive DLI along with IMiDs and/or cyclophosphamide, and prospective trials are warranted [136, 143, 144]. A number of smaller, non-controlled allo SCT studies have also been published reporting long term survival even in patients with high risk cytogenetics [130, 134, 145–148]. The later suggests that allo SCT might be able to overcome adverse cytogenetic features, and justifies further clinical evaluation in this group of patients.…”

Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

Immunologic approaches for the treatment of multiple myeloma

Rasche

Weinhold

Morgan

et al. 2017

Cancer Treatment Reviews

View full text Add to dashboard Cite

The FDA approval of two monoclonal antibodies in 2015 has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, ‘off-target’ immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies. We also describe some of the limitations of the current strategies and speculate on the future of personalized immunotherapies for MM.

show abstract

“…The role of allogeneic stem cell transplantation (alloSCT) as treatment option for relapsed MM is currently under debate. [2][3][4][5][6][7][8] However, important lessons can be learned from the effect of T-cell therapy in the context of alloSCT. This may help to further develop T-cell therapy exploiting chimeric antigen receptor (CAR) cells, which is increasingly being performed.…”

Section: Introductionmentioning

confidence: 99%

Donor T-cell responses and disease progression patterns of multiple myeloma

Eefting

Wreede

Borne

et al. 2017

Bone Marrow Transplant

View full text Add to dashboard Cite

Donor T-cells transferred after allogeneic stem cell transplantation (alloSCT) can result in long-term disease control in myeloma by the graft-versus-myeloma (GvM) effect. However, T-cell therapy may show differential effectiveness against bone marrow (BM) infiltration and focal myeloma lesions resulting in different control and progression patterns. Outcomes of 43 myeloma patients who underwent T-cell-depleted alloSCT with scheduled donor lymphocyte infusion (DLI) were analyzed with respect to diffuse BM infiltration and focal progression. For comparison, 12 patients for whom a donor search was started but no alloSCT was performed, were analyzed. After DLI, complete disappearance of myeloma cells in BM occurred in 86% of evaluable patients. The probabilities of BM progression-free survival (PFS) at 2 years after start of donor search, alloSCT and DLI, were 17% (95% confidence interval 0-38%), 51% (36-66%), and 62% (44-80%) respectively. In contrast, the probabilities of focal PFS at 2 years after start of donor search, alloSCT and DLI, were 17% (0-38%), 30% (17-44%) and 28% (11-44%), respectively. Donor-derived T-cell responses effectively reduce BM infiltration, but not focal progression in myeloma, illustrating potent immunological responses in BM with only limited effect of T-cells on focal lesions.

show abstract

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Cited by 13 publications

References 56 publications

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Immunologic approaches for the treatment of multiple myeloma

Donor T-cell responses and disease progression patterns of multiple myeloma

Contact Info

Product

Resources

About