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Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation.

ABSTRACT: Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival (RFS) was 60% with LIT with venetoclax vs 54% with IC, and 41% with LIT without venetoclax; the 2-year overall survival (OS) was 72% LIT with venetoclax vs 58% with IC, and 41% with LIT without venetoclax. The benefit of LIT with venetoclax induction was greatest in patients with adverse-risk AML (2-year OS: 74%, 46%, and 29%, respectively). Induction with LIT, with or without venetoclax, was associated with the lowest rate of nonrelapse mortality (NRM) (2-year NRM: 17% vs 27% with IC; P = .04). Using multivariate analysis, the type of induction therapy did not significantly affect any of the post HSCT outcomes evaluated; hematopoietic cell transplantation-specific comorbidity index was the only factor that independently predicted RFS and OS. LIT plus venetoclax followed by HSCT is a feasible treatment strategy in older, fit, HSCT-eligible patients with newly diagnosed AML and may be particularly beneficial for those with adverse-risk disease.

SUBMITTER: Short NJ

PROVIDER: S-EPMC10368841 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation.

Short Nicholas J NJ Ong Faustine F Ravandi Farhad F Nogueras-Gonzalez Graciela G Kadia Tapan M TM Daver Naval N DiNardo Courtney D CD Konopleva Marina M Borthakur Gautam G Oran Betul B Al-Atrash Gheath G Mehta Rohtesh R Jabbour Elias J EJ Yilmaz Musa M Issa Ghayas C GC Maiti Abhishek A Champlin Richard E RE Kantarjian Hagop H Shpall Elizabeth J EJ Popat Uday U

Blood advances 20230701 14

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; ...[more]

PMID: 37104058

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Project description:Allogeneic hematopoietic cell transplantation (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit for alloHCT with matched unrelated donors (MUDs), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) versus the best MUD? This retrospective cohort registry study accessed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients with AML age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included nonrelapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival. Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD (median donor age, 60 years), and 2948 underwent alloHCT from a younger MUD (median donor age, 25 years). In multivariable analysis, compared to older MSDs, the use of younger MUDs conferred a decreased relapse risk (hazard ratio [HR], .86; P = .005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% versus 41%; P = .003), but was associated with an increased risk for chronic GVHD (HR, 1.18; 95% confidence interval [CI], 1.08 to 1.29; P = .0002) and greater NRM only in the earlier period of 2011 to 2015 (HR, 1.24; P = .016). The corresponding NRM rates were significantly lower in the more recent period of 2016 to 2018 (HR, .78; P = .017). The adjusted 5-year DFS probability was 44% (95% CI, 42% to 46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38% to 43%) with older MSDs (P = .04). In summary, for older patients with AML undergoing alloHCT, the use of younger MUDs is associated with decreased relapse risk and improved DFS compared with the use of older MSDs.

Project description:Allogeneic stem cell transplantation (allo-SCT) is the preferred curative treatment for several hematological malignancies. The efficacy of allo-SCT depends on the graft-versus-leukemia (GvL) effect. However, the prognosis of patients with relapsed acute myeloid leukemia (AML) following allo-SCT is poor. Donor lymphocyte infusion (DLI) is utilized after allo-SCT in this setting to prevent relapse, to prolong progression free survival, to establish full donor chimerism and to restore the GvL effect in patients with hematological malignancies. Thus, there are different options for the administration of DLI in AML patients. DLI is currently used prophylactically and in the setting of an overt relapse. In addition, in the minimal residual disease (MRD) setting, DLI may be a possibility to improve overall survival. However, DLI might increase the risk of severe life-threatening complications such as graft-versus-host disease (GvHD) as well as severe infections. The transfusion of lymphocytes has been tested not only for the treatment of hematological malignancies but also chronic infections. In this context, manipulated DLI in a prophylactic or therapeutic approach are an option, e.g., virus-specific DLI using different selection methods or antigen-specific DLI such as peptide-specific CD8+ cytotoxic T lymphocytes (CTLs). In addition, T cells are also genetically engineered, using both chimeric antigen receptor (CAR) genetically modified T cells and T cell receptor (TCR) genetically modified T cells. T cell therapies in general have the potential to enhance antitumor immunity, augment vaccine efficacy, and limit graft-versus-host disease after allo-SCT. The focus of this review is to discuss the different strategies to use donor lymphocytes after allo-SCT. Our objective is to give an insight into the functional effects of DLI on immunogenic antigen recognition for a better understanding of the mechanisms of DLI. To ultimately increase the GvL potency without raising the risk of GvHD at the same time.

Dataset Information

Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation.

Publications

Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation.

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