Time from autologous to allogeneic hematopoietic stem cell transplantation impacts post-transplant outcomes in multiple myeloma

Fiorenza, Salvatore; Routledge, David; Collins, Jenny; Shipton, Michael J; Harrison, Simon; Bajel, Ashish; Cavet, James; Tholouli, Eleni; Gauthier, Jordan; Ritchie, David

doi:10.1038/s41409-019-0642-x

Cited by 5 publications

(7 citation statements)

References 8 publications

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“…The intensity and duration of preceding therapy are associated with outcomes after allogeneic SCT, similar to findings from previous retrospective studies [3,27]. Patients transplanted in first or second line had superior OS and PFS as compared with patients with 3 and more lines of therapy before transplantation.…”

Section: Discussionsupporting

confidence: 81%

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

et al. 2020

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Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.

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Section: Discussionsupporting

confidence: 81%

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

et al. 2020

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“… 25 , 34 The first immunotherapy for MM was an allogeneic stem cell transplant, which remains a routine treatment for the long‐term management of high‐risk diseases. 35 In the mid‐2000s, immunomodulatory drugs designed to improve the immunomodulatory and anticancer properties and tolerability profiles of treatments; such as thalidomide, were shown to be effective in MM and substantially improved survival. 36 The next generation of immunotherapies for MM comprises monoclonal antibodies, 37 chimeric antigen receptor T cells, 38 bispecific antibodies, 39 antibody drug conjugates, 40 and checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Identification of three immune molecular subtypes associated with immune profiles, immune checkpoints, and clinical outcome in multiple myeloma

Gao

Fang

et al. 2021

Cancer Medicine

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Purpose To identify the immune molecular subtype for MM to help achieve individualized and precise targeted therapy. Methods The GDC API was used to download the TCGA‐MM profile dataset, which contains 859 samples in total, all of which were anterior to the standard treatment after diagnosis. Moreover, 282, 298, and 258 samples were stage I, stage II, and stage III separately. We used the immune gene expression profile for consistent clustering; and used the R software package ConsensusClusterPlus to sort the immune molecular subtypes. Correlation between subtypes and clinical features, immunity, and prognosis was then analyzed. Results A total of 859 tumor samples were separated into these three subtypes, which were not meaningfully related to age or sex but showed a remarkable association with stage. The results suggested that obvious differences in immune metagene expression and expression of 10 immune checkpoint genes appeared among the three subtypes. Conclusion The three subtypes are distinctly different in terms of immune metagenes, immune checkpoint molecules, and clinical prognosis. The discovery of the immune microenvironment of MM could further reveal the strategy for immunotherapy in MM and provide a promising candidate prognostic tool for survival.

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“…In various studies remission status at allo-SCT was also a relevant predictor for survival with significantly longer OS and/or PFS in patients responding to induction as compared to those with progressive disease at the time point of transplantation [ 17 , 18 , 36 , 43 , 45 , 51 , 67 , 75 , 77 , 78 , 80 , 81 , 82 ]. The role of minimal residual disease (MRD)-status was analyzed in the post-transplant setting and is not conclusively clarified at this time: Achievement of MRD-negativity by flow cytometry after transplantation led to a survival benefit in a large retrospective analysis [ 76 ], whereas another trial could not prove a difference [ 82 ].…”

Section: Prognostic Factorsmentioning

confidence: 99%

“…Expectedly, younger patient age [ 73 , 75 , 78 , 80 , 82 ], a good performance status [ 43 ] and participation in clinical trials [ 44 ] were found to be associated with a better outcome.…”

Section: Prognostic Factorsmentioning

confidence: 99%

Allogeneic Stem Cell Transplantation in Multiple Myeloma

Greil

Engelhardt

Finke

et al. 2021

Cancers

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The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

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Time from autologous to allogeneic hematopoietic stem cell transplantation impacts post-transplant outcomes in multiple myeloma

Cited by 5 publications

References 8 publications

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

Identification of three immune molecular subtypes associated with immune profiles, immune checkpoints, and clinical outcome in multiple myeloma

Allogeneic Stem Cell Transplantation in Multiple Myeloma

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