Use of a more intense reduced-intensity conditioning and non-myeloablative conditioning (RIC-NMAC) regimen for allogeneic hematopoietic cell transplant (HCT) in patients with non-Hodgkin lymphoma should be considered with caution, according to results of a recent investigation published in JAMA Oncology (online June 4, 2020; doi:10.1001/jamaoncol.2020.1278).
RIC-NMAC regimens are often used in allogeneic HCT for patients with non-Hodgkin lymphoma. However, there is limited consensus regarding the optimal RIC-NMAC regimen for this patient population.
Nilanjan Ghosh, MD, PhD, department of hematologic oncology and blood disorders, Levine Cancer Institute (Charlotte, NC), and colleagues investigated whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased non-relapse mortality and lower overall survival (OS) compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. A total of 1823 patients were included from the Center for International Blood and Marrow Transplant Research registry who underwent allogeneic HCT between January 2008 and December 2016.
Patients received any of four RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu; n = 458), fludarabine-melphalan (Flu-Mel140; n – 885), fludarabine-cyclophosphamide (Flu-Cy; n = 391), or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI; n = 89). The statistical analysis was performed from June 1, 2019, to February 10, 2020.
Dr Ghosh and colleagues found that the 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001).
After adjusting for age, Karnofsky performance score, HCT comorbidity index, non-Hodgkin lymphoma subtype, remission status at HCT, and use of antithymocyte globulin or alemtuzumab, there was a significantly higher mortality risk observed with Flu-Mel140 compared with Flu-Bu (HR, 1.34; 95% CI, 1.13-1.59; P < .001).
Additionally, researchers found that the Flu-Mel140 cohort had a higher risk of chronic graft-versus-host disease than the Flu-Cy cohort (HR, 1.38; 95% CI, 1.15-1.65; P < .001).
The Flu-Mel140 regimen was associated with a higher non-relapse mortality risk compared with the Flu-Bu regimen, they added (HR, 1.78; 95% CI, 1.37-2.31; P < .001).
“The findings suggest that use of the more intense RIC-NMAC regimen FluMel140 may have a negative association with OS and may be associated with higher non-relapse mortality,” authors of the study concluded. “The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable OS.”—Zachary Bessette
