Dr. Schetelig on the Use of Induction Chemotherapy Prior to Allo-HCT in Relapsed/Refractory AML

Johannes Schetelig, MD, MSc, head, Stem Cell Transplantation Unit, University Hospital TU Dresden, head, DKMS Clinical Trials Unit, discusses whether patients with active relapsed/refractory acute myeloid leukemia (AML) should receive remission induction chemotherapy prior to undergoing allogenic hematopoietic stem cell transplant (allo-HCT).

In the United States, there is a notable reluctance among physicians to regard immediate transplantation as a viable therapeutic option for patients with AML, Schetelig begins. This hesitancy stems from historical evidence illustrating suboptimal outcomes associated with promptly proceeding to transplant in this patient cohort, he explains. The typical clinical scenario involves patients who have exhausted multiple treatment approaches attempting to achieve a complete remission, Schetelig says, noting that these patients are often the most challenging cases.

Despite a growing emphasis on the significance of early transplantation in certain European countries, conventional treatment strategies involve the use of targeted therapy to induce complete remission before proceeding to transplant, Schetelig continues. Targeted therapy combinations are the preferred initial choice, and these approaches have shown promise in select patient populations, Schetelig states. Patients who remain unresponsive to these therapies in the first- or second-line will go on to receive intensive combination chemotherapy. However, there is a lack of retrospective and prospective evidence showing that patients benefit more from these intensive chemotherapy approaches prior to transplant, Schetelig emphasizes.

For example, the phase 3 ASAP trial (NCT02461537) assessed whether patients would experience greater overall survival (OS) and disease-free survival (DFS) benefit with sequential conditioning and immediate allo-HCT vs intensive induction chemotherapy followed by allo-HCT to induce a complete response (CR) before transplantation. Results demonstrated that watchful waiting and sequential conditioning prior to allo-HCT produced OS and CR rates that were comparable those who received induction chemotherapy.

Although salvage chemotherapy prior to allo-HCT does not produce inferior survival outcomes vs immediate allo-HCT, these data confirm that it does not provide a sufficient survival advantage. Accordingly, watchful waiting prior to alloHCT should be considered as a viable approach in this population.