Among patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic transplant, higher intensity reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) is positively associated with an increase in nonrelapse mortality, according to findings published in JAMA Oncology.

Nilanjan Ghosh, MD, PhD, of the department of hematologic oncology and blood disorders at the Levine Cancer Institute, Atrium Health in Charlotte, North Carolina, and associates conducted a cohort study to determine whether higher intensity RIC-NMAC regimens are linked to an increase in nonrelapse mortality rates and lower overall survival compared with lower intensity regimens among patients with NHL undergoing allogeneic hematopoietic stem cell transplantation.

The main outcome was overall survival. Secondary outcomes included nonrelapse mortality, relapse incidence, progression-free survival, and any incidence of acute or chronic graft-vs-host disease (GVHD).

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A total of 1823 adults (average age, 54.8 years; 65% men) with NHL were randomly assigned to receive 1 of 4 RIC-NMAC treatments: 458 patients were treated with fludarabine-intravenous busulfan (Flu-Bu) about 6.4 mg/kg, 885 patients were treated with fludarabine-melphalan (Flu-Mel140) about 140 mg/m2, 391 patients were treated with fludarabine-cyclophosphamide (Flu-Cy), and 89 patients were treated with Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI).

The 4-year adjusted overall survival rates for patients in the Flu-Bu, Flu-Mel140, Flu-Cy, and Flu-Cy-2GyTBI groups were 58%, 49%, 63%, and 67%, respectively (P <.001). Following statistical adjustments, the regression analysis suggested a significant mortality risk with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34), Flu-Cy-2GyTBI (HR, 1.82), and Flu-Cy (HR, 1.59).

In addition, the 4-year adjusted cumulative incidence of nonrelapse mortality rates for patients in the Flu-Bu, Flu-Mel140, Flu-Cy, and Flu-Cy-2GyTBI groups were 16%, 26%, 17%, and 17%, respectively (P <.001). Following adjustments, Flu-Mel140 was significantly associated with risk for nonrelapse mortality compared with Flu-Bu (HR, 1.78).

Progression-free survival was not statistically significant (P =.07) and was lowest for patients in the Flu-Cy cohort (35%) and highest for patients in the Flu-Cy-2GyTBI cohort (51%). 

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In addition, patients in the Flu-Mel140 cohort had a higher risk of developing chronic GVHD compared with patients in the Flu-Cy cohort (HR, 1.38; P <.001).

“The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival,” the investigators wrote.

The researchers concluded that these results may be practice changing and highlight that their findings should caution against the use of high-intensity regimens in patients with NHL.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Ghosh N, Ahmed S, Ahn KW, et al. Association of reduced-intensity conditioning regimens with overall survival among patients with non-Hodgkin lymphoma undergoing allogeneic transplant [published online June 4, 2020]. JAMA Oncol. doi: 10.1001/jamaoncol.2020.1278