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Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.

ABSTRACT: Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We obtained individual patient data from participants of four trials comparing auto-auto vs. auto-allo after induction therapy. There were 899 patients in auto-auto and 439 in auto-allo. Median follow up of survivors was 118.5 months. Median overall survival (OS) was 78.0 months in auto-auto and 98.3 months in auto-allo (HR?=?0.84, P?=?0.02). OS was 36.4% vs. 44.1% at 10 years (P?=?0.01) for auto-auto and auto-allo, respectively. Progression-free survival was also improved in auto-allo (HR?=?0.84, P?=?0.004). Risk of non-relapse mortality was higher in auto-allo (10 year 8.3% vs. 19.7%, P?

SUBMITTER: Costa LJ

PROVIDER: S-EPMC7483973 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.

Costa Luciano J LJ Iacobelli Simona S Pasquini Marcelo C MC Modi Riddhi R Giaccone Luisa L Blade Joan J Schonland Stefan S Evangelista Andrea A Perez-Simon Jose A JA Hari Parameswaran P Brown Elizabeth E EE Giralt Sergio A SA Patriarca Francesca F Stadtmauer Edward A EA Rosinol Laura L Krishnan Amrita Y AY Gahrton Gösta G Bruno Benedetto B

Bone marrow transplantation 20200414 9

Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We ...[more]

PMID: 32286506

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Project description:We previously reported initial results in 102 multiple myeloma (MM) patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m2 and allogeneic hematopoietic cell transplantation. Here we present long-term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow up of 8.3 (range 1.0-18.1) years. Donors included human leukocyte antigen identical siblings (n=179) and HLA-matched unrelated donors (n=65). A total of 209 patients (86%) received tandem autologous-allogeneic upfront, while thirty-five patients (14%) had failed a previous autologous hematopoietic cell transplantation before the planned autologous-allogeneic transplantation. Thirty-one patients received maintenance treatment at a median of 86 days (range, 61-150) after allogeneic transplantation. Five-year rates of overall survival (OS) and progression-free survival (PFS) were 54% and 31%, respectively. Ten-year OS and PFS were 41% and 19%, respectively. Overall non-relapse mortality was 2% at 100 days and 14% at five years. Patients with induction-refractory disease and those with high-risk biological features experienced shorter OS and PFS. A total of 152 patients experienced disease relapse and 117 of those received salvage treatment. Eighty-three of the 117 patients achieved a clinical response, and for those, the median duration of survival after relapse was 7.8 years. Moreover, a subset of patients who became negative for minimal residual disease (MRD) by flow cytometry experienced a significantly lower relapse rate as compared with MRD-positive patients (P=0.03). Our study showed that the graft-versus-myeloma effect after non-myeloablative allografting allowed long-term disease control in standard and high-risk patient subsets. Ultra-high-risk patients did not appear to benefit from tandem autologous/allogeneic hematopoietic cell transplantation because of early disease relapse. Incorporation of newer anti-MM agents into the initial induction treatments before tandem hematopoietic cell transplantation and during maintenance might improve outcomes of ultra-high-risk patients. Clinical trials included in this study are registered at: clinicaltrials.gov identifiers: 00075478, 00005799, 01251575, 00078858, 00105001, 00027820, 00089011, 00003196, 00006251, 00793572, 00054353, 00014235, 00003954.

Dataset Information

Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.

Publications

Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.

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