The pro-oxidant molecule imexon (Amplimexon/NSC-714597) produced an overall response rate of 30% in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) participating in a phase II study. Noting that “lymphoma cells are subject to higher levels of oxidative stress than their normal counterparts,” the investigators hypothesized that the lymphoma cells “may be vulnerable to manipulations of the cellular redox balance.”
The results of the trial represent “the first demonstration of clinical activity with a pro-oxidant molecule in lymphoma, Paul M. Barr, MD, of the University of Rochester Wilmot Cancer Center, New York, and colleagues reported in Blood. They also found that antioxidant-related gene expression predicted for response to imexon.
The trial enrolled 22 patients with a variety of non-Hodgkin lymphomas: 9 with follicular, 5 with diffuse large B-cell, 3 with mantle cell, 2 with transformed follicular, 2 with small lymphocytic, and 1 with Burkitt lymphoma. The median number of prior therapies received was four, and all patients had received previous anti-CD20 antibody therapy. The median age was 64.
Imexon was administered at 1,000 mg/m2 intravenously for the first 5 days in 21-day cycles and continued until disease progression or unacceptable toxicity. The 30% overall response rate (P = .011) for the 20 evaluable patients included 4 patients with follicular lymphoma and 2 with diffuse large B-cell lymphoma. “All 6 responding patients achieved a partial response; an additional 35% of patients achieved stable disease,” the researchers reported.
The most common adverse event of any grade was fatigue, occurring in 91% of patients. The most common grade 3/4 adverse events were anemia, occurring in 14% of patients, and neutropenia in 9%. Two patients died while on study, one with progressive diffuse large B-cell lymphoma and one with a septic event.
“Gene expression analyses revealed CD68 and the redox related genes, GPX1 and SOD2, as well as a higher redox score to correlate with clinical responses,” the researchers reported. “Pre-treatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach,” the authors added.
This study was registered at ClinicalTrials.gov with the identifier NCT01314014. ■
Barr PM, et al: Blood. July 11, 2014 (early release online).