Allogeneic Hematopoietic Cell Transplantation Versus Best Available Standard of Care Therapy in Elderly Patients With Acute Myeloid Leukemia: a Randomized Phase 3 Trial
Allogeneic Hematopoietic Cell Transplantation Versus Best Available Standard of Care Therapy in Elderly Patients With Acute Myeloid Leukemia: a Randomized Phase 3 Trial
A subject of major interest for researchers, clinicians, patients, and payers, is the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of these older patients with AML. With conventional induction chemotherapy or hypomethylating agents, the expected 2-year overall survival (OS) is less than 25% in patients with intermediate- or high-risk disease. The 2-year OS ranges from 50 to 56% with allo-HSCT in AML patients older than 65 years.
Performing an allo-HSCT in older patients is however still controversial because of the higher risk of non-relapse mortality (15 to 35%) and graft-versus-host disease. Depending on the center policy, patients older than 65 years will either be contraindicated for transplant or will receive allo-HSCT.
With a phase III comparative, randomized, controlled, prospective, multicenter study, the trial aim to assess prospectively the outcomes and quality of life of older patients with AML receiving allo-HSCT strategy compared to those receiving a non-transplant approach.
Every year, 30,000 patients in Europe and 20,000 in the USA are diagnosed with acute myeloid leukemia (AML). More than half of them are over 65 years old. In this older population, the median overall survival (OS) is only 2 to 8 months. With conventional induction chemotherapy or hypomethylating agents, the expected 2-year OS is less than 25% in patients with intermediate- or high-risk disease.
Performing an allo-HSCT in older patients is however still controversial because of the higher risk of non-relapse mortality (15 to 35%) and graft-versus-host disease. Depending on the center policy, patients older than 65 years will either be contraindicated for transplant or will receive allo-HSCT. Noteworthy, no prospective randomized trial has yet compared allo-HSCT to a non-transplant strategy in older patients with AML. A previous attempt made 10 years ago, by the EBMT to run a slightly similar trial, has failed in France and most European countries, mainly (i) because it mandated the type of transplant procedure to be applied and (ii) because of the absence of novel and effective drugs.
Every year, 30,000 patients in Europe and 20,000 in the USA are diagnosed with acute myeloid leukemia (AML). More than half of them are over 65 years old. In this older population, the median overall survival (OS) is only 2 to 8 months. With conventional induction chemotherapy or hypometylating agents, the expected 2-year OS is less than 25% in patients with intermediate- or high-risk disease.
Performing an allo-HSCT in older patients is however still controversial because of the higher risk of non-relapse mortality (15 to 35%) and graft-versus-host disease. Depending on the center policy, patients older than 65 years will either be contraindicated for transplant or will receive allo-HSCT. Noteworthy, no prospective randomized trial has yet compared allo-HSCT to a non-transplant strategy in older patients with AML. A previous attempt made 10 years ago, by the EBMT to run a slightly similar trial, has failed in France and most European countries, mainly (i) because it mandated the type of transplant procedure to be applied and (ii) because of the absence of novel and effective drugs.
New targeted therapies and treatment strategies are evolving rapidly. A standardized unique treatment administrated to all sub-types of AML is no longer the optimal approach for induction and non-transplant maintenance strategies. No treatment has reached consensus for older patients. For these reasons, this trial will not limit the choices of drugs administered to the patients but compare two strategies allowing patients to receive the best available standard of care.
The trial aim to assess prospectively the outcomes and quality of life of older patients with AML receiving allo-HSCT strategy compared to those receiving a non-transplant approach.
Patients will receive initial treatment with chemotherapy (or other appropriate non-palliative therapy). Once first complete remission is achieved and a donor is identified, patients will be included.
Patients will be randomly assigned (1:1) after inclusion to receive one of the following strategy:
All patients will receive the best available treatments (including additional conventional chemotherapy or other non-palliative therapies such as 5-azacytidine, decitabine, venetoclax, midaustorine, enasidenib, etc.). Supportive care will be performed according to each participating center usual practice.
Inclusion Criteria:
Exclusion Criteria: