Outcome of allogeneic transplantation in newly diagnosed and relapsed/refractory multiple myeloma: long‐term follow‐up in a single institution

Franssen, Laurens E.; Raymakers, Reinier; Buijs, Arjan; Schmitz, M.F.; Dorp, Suzanne van; Mutis, Tuna; Lokhorst, Henk M.; Donk, Niels W.C.J. van de

doi:10.1111/ejh.12758

Cited by 17 publications

(23 citation statements)

References 48 publications

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“…We did not find a significant difference in PFS or OS between patients with high-risk genetic features and those without, an encouraging finding that will need further study because of the small number of patients in a retrospective analysis. However, similar finding have been seen with alloBMT in high-risk MM using other forms of GVHD prophylaxis [41–45]. …”

Section: Discussionsupporting

confidence: 78%

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

Ghosh¹,

Tsai

et al. 2017

Biology of Blood and Marrow Transplantation

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Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high non-relapse mortality (NRM) rates primarily from graft versus host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD rates following alloBMT. Here we examine the impact of PTCy in MM patients undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors following either myeloablative or non-myeloablative conditioning. Post-transplant GVHD prophylaxis consisted of cyclophosphamide (50mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients with median neutrophil and platelet recovery at 15 and 16 days, respectively. The cumulative incidence of acute grade 2–4 and grade 3–4 GVHD was 0.41 and 0.08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was 0.13. Only one patient succumbed to NRM. All cases of chronic GVHD involved extensive disease, and 60% of these patients received systemic therapy with complete resolution. Following alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was 0.46 (95% CI: 0.3–0.62) at one year and 0.56 (95% CI: 0.41–0.72) at two years. At last follow up, 23% of patients remain without evidence of disease at a median follow up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5 and 10-year overall survival probabilities were 49% (95%CI:35–67%) and 43% (95%CI:29–62%), respectively. The use of PTCy following alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplant maintenance strategies to improve long-term disease control.

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Section: Discussionsupporting

confidence: 78%

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

Ghosh¹,

Tsai

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Although overall response rates and OS have been increased, most patients still relapsed soon. All 14 trials involved in our study showed that high cytogenetic risk patients after allo-SCT had similar OS and PFS to those with standard-risk (RR = 0.83, 95% CI 0.67–1.03) [ 12 , 14 , 15 , 21 , 25 , 31 , 39 , 42 – 44 , 47 , 50 , 51 , 57 , 58 ]. However, most trials described the situation using descriptive language, only 5 provided concrete data of comparisons of OS between high cytogenetic risk patients and standard-risk patients [ 15 , 25 , 42 , 44 , 57 ].…”

Section: Resultsmentioning

confidence: 76%

“…Some studies indicated that disease status in remission at transplantation and post transplantation could be prognostic factor indexes for improving OS. The pooled analysis of 7 trials for patients at transplantation in complete remission (CR) [ 15 , 26 , 40 , 47 , 50 – 52 ] and 3 trials for patients post-transplantation in CR [ 21 , 50 , 51 ] showed that patients at transplantation (HR = 0.43, 95% CI 0.29–0.63) or post transplantation (HR = 0.36, 95% CI 0.17–0.76) in CR had higher OS than those in non-CR.…”

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

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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.

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“…Poorer outcome in the relapsed setting has been previously reported by Franssen and colleagues, who also did not see any differences in outcome for patients with high risk cytogenetics, as was the case in our own investigation. 32 …”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of tumor burden assessed by whole-body magnetic resonance imaging in multiple myeloma patients treated with allogeneic stem cell transplantation

et al. 2017

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Allogeneic stem cell transplantation is a therapeutic option under dispute but nonetheless chosen with increasing frequency for patients suffering from multiple myeloma in Europe. To study possible predictors of survival, 79 patients were investigated using whole-body magnetic resonance imaging to assess the visible tumor burden before and after allogeneic stem cell transplantation. Statistical analysis of clinical and imaging parameters included Cox regression models and distribution of survival time estimates (Kaplan-Meier method). Log rank test was used to determine the prognostic impact of the presence of focal lesions on survival. A higher tumor burden according to the lesion count was associated with a shorter overall survival (univariable/multivariable Cox regression: 1st magnetic resonance imaging P=0.028/P=0.048; 2nd magnetic resonance imaging P=0.008/P=0.024). Focal infiltration pattern itself seemed to be an additional adverse prognostic factor for overall survival (2nd MRI P=0.048), although no definite cut-off could be defined. Kaplan-Meier estimates at 60 months of follow up show a significant difference (Log rank P=0.04) for overall survival rates between patients with focal infiltration (32%) and those without (75%). Since this subgroup of patients may benefit from maintenance therapy, adoptive immunotherapy, or local interventions, whole-body imaging is an appropriate and highly recommendable diagnostic approach for detection of prognostically relevant lesions before and after treatment.

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Outcome of allogeneic transplantation in newly diagnosed and relapsed/refractory multiple myeloma: long‐term follow‐up in a single institution

Cited by 17 publications

References 48 publications

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

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

Prognostic significance of tumor burden assessed by whole-body magnetic resonance imaging in multiple myeloma patients treated with allogeneic stem cell transplantation

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