Can Nivolumab Maintain AML Remission?

Medscape

23-05-2025

In a randomized phase 2 study of 79 patients with acute myeloid leukemia (AML) in first complete remission, nivolumab maintenance therapy did not improve progression-free survival (13.2 vs 10.9 months) or overall survival (53.9 vs 30.9 months) compared with observation. Adverse events were more frequent in the nivolumab arm, with 71% experiencing grade ≥ 3 events vs 12% in the observation arm.
METHODOLOGY:
A multicenter, open-label, randomized phase 2 trial enrolled 79 patients with AML in first complete remission or complete remission with incomplete hematologic recovery who were not candidates for stem cell transplant.
Participants were randomized to either observation or nivolumab arm (3 mg/kg intravenously every 2 weeks for 46 doses), with a median follow-up duration of 24 months.
Primary endpoint was progression-free survival, defined as time to disease relapse or death, while secondary endpoints included overall survival and evaluation of adverse events.
Analysis included measurement of measurable residual disease (MRD) through ultrasensitive duplex DNA sequencing in 55 patients and targeted RNA sequencing in two patients before randomization.
TAKEAWAY:
Median progression-free survival duration was 13.2 months (95% CI, 8.5-21.8) in the nivolumab arm vs 10.9 months (95% CI, 5.4-14.9) in the observation arm (hazard ratio [HR], 0.92; 95% CI, 0.54-1.56; P = .38).
= .38). Overall survival analysis showed median survival duration of 53.9 months (95% CI, 23.4 to not estimable) in the nivolumab arm vs 30.9 months (95% CI, 14.4 to not estimable) in the observation arm (HR, 0.78; 95% CI, 0.40-1.51; P = .23).
= .23). Adverse events of grade ≥ 3 occurred in 71% of nivolumab-treated patients compared with 12% of patients in the observation arm ( P < .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common.
< .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common. MRD positive patients showed significantly higher relapse rates at 2 years (74% vs 37%; P = .046) and decreased progression-free survival (21% vs 63%; P = .032) than MRD negative patients.
IN PRACTICE:
'With negative results using checkpoint inhibitors alone (or in combination with HMA [hypomethylating agent]), now in both the MRD setting and in the front line, the utility of targeting the PD1-PDL1 [programmed cell death 1–programmed death ligand 1] pathway in unselected AML appears limited…. It remains possible that further correlatives studies might identify a subset of patients with AML who may responses to immune checkpoint inhibition,' wrote the authors of the study.
SOURCE:
The study was led by Athalia Pyzer and Hongtao Liu, The University of Chicago in Chicago. It was published online on May 13 in Blood Advances .
LIMITATIONS:
According to the authors, subgroup analysis in the cohort of MRD positive patients did not demonstrate any effect of nivolumab on clinical outcomes, but these comparisons were underpowered. The researchers noted that other immune escape mechanisms, even beyond checkpoint pathways, likely contribute to the persistence of this disease.
DISCLOSURES:
The study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, a University of Chicago Comprehensive Cancer Center pilot grant, the Ullman Scholar Award, and the Elsa U. Pardee Foundation. Additional disclosures are noted in the original article.