First-of-Kind Trial Studies OS in Post-allograft–Relapsed AML

October 10, 2018
Naveed Saleh, MD, MS
Naveed Saleh, MD, MS

The research, published in JAMA Oncology, evaluates survival outcomes of a second allogeneic hematopoietic cell transplant vs donor lymphocyte infusion.

Allogeneic hematopoietic cell transplant or donor lymphocyte infusion (DLI) offered better overall survival (OS) in patients with post-allograft–relapsed acute myeloid leukemia (AML) who relapsed 6-plus months after a first allogeneic hematopoietic cell transplant (allo-HCT1) or who attained complete remission at the time of second allo-HCT (allo-HCT2) or DLI, according to a recent study published in JAMA Oncology.

“The optimal treatment approach to patients with AML who relapse after an allo-HCT remains elusive,” wrote the authors, led by Mohamed A. Kharfan-Dabaja, MD, MBA, of the Division of Hematology-Oncology in the Blood and Marrow Transplantation Program at the Mayo Clinic in Jacksonville, Florida. “No randomized clinical trial comparing survival outcomes of an allo-HCT2 vs DLI has been conducted to date.”

AML is a diverse and complex disease that belies conventional treatment algorithms, which are based on only clinical and cytogenetic characteristics. Allo-HCT can cure AML, depending on the remission status at the time of the allograft, with overall survival (OS) rates of between 15% and 30% in relapsed/refractory disease and between 50% and 75% in patients who receive allografts during the initial complete remission (CR). Importantly, relapse still occurs in between 25% and 30% of such patients, even with the administration of myeloablative regimens.

With post-allograft–relapsed AML, the calculus to administer either allo-HCT2 or DLI is multifactorial and includes donor availability, remission status, presence of disabling comorbidities, and the center or physician preference.

In the current retrospective registry study, the researchers included 418 adults (54.5% men; average age, 46.2 years) who were administered either an allo-HCT2 (N=137) or one or more DLIs (N=281) for post-allograft–relapsed AML. The primary outcomes in the study were OS at 2 or 5 years following allo-HCT2 or DLI. Median follow-up for all patients was 63 months.

With respect to the primary outcomes, Kharfan-Dabaja et al found no significant difference in OS in post-allograft–relapsed AML patients who then received either allo-HCT2 or DLI at 2 years or 5 years (P = .86). Specifically, 2-year OS in allo-HCT2 was 26% vs 25% in DLI. Furthermore, the 5-year OS was 19% in allo-HCT2 vs 15% in DLI.

The researchers found that OS was boosted in patients who were in complete remission at the time of receiving either allo-HCT2 or DLI (HR, 0.55; 95% CI, 0.41–0.74; P < .001). Furthermore, 5-year OS was lowest in patients who relapsed within 6 months after allo-HCT1 despite whether they received allo-HCT2 or DLI (9% for allo-HCT2 vs 4% for DLI; P = .86).

Based on the results of the study, the researchers could not recommend either allo-HCT2 or DLI in post-allograft–relapsed AML due to patient, disease, and treatment heterogeneity. Nonetheless, OS seems to be equal with both approaches.

“Best results seem to be achieved in patients who relapse after 6 months from an allo-HCT1 or those who attain CR prior to an allo-HCT2 or DLI,” the researchers concluded. “In patients who relapse within less than 6 months or receive an intervention while having active disease, OS rates are low.”

One limitation of the current study is that the researchers were unable to determine why specialists preferred allo-HCT2 or DLI in the sample.

“The take home points for me are, first of all, the outcomes of any and all treatments for relapsed AML following prior allogeneic hematopoietic stem cell treatment are almost universally fatal,” Eunice S. Wang, MD, professor of oncology at the University of Buffalo’s Jacobs School of Medicine and Biomedical Sciences, told Cancer Network. “Five-year survival in this setting with DLI or alloSCT is the same: 15% for all patients. As one would expect, patients treated in CR did better than those treated in overt relapse, and those whose disease recurred within 6 months of first alloSCT had more resistant disease. The implications of this study are clear: The currently available therapies for patients in this setting do equally poorly, and novel approaches to address this, perhaps by integrating novel immunotherapeutic or targeted agents, are desperately needed,” Wang said.