SAN DIEGO – Maintain with more rituximab or re-treat? For patients with low tumor burden follicular lymphomas, the answer seems to be that it doesn’t much matter, said investigators at the annual meeting of the American Society of Hematology.
Following 4 weeks of induction with rituximab monotherapy, time to treatment failure (TTTF), the primary end point, was virtually identical between patients randomized to 12 weeks of rituximab (Rituxan) maintenance (3.9 years) or rituximab re-treatment at progression (3.6 years, P = .80) in the E4402 RESORT (Rituximab Extended Schedule or Re-Treatment Trial) study.
One year after randomization, there were no significant differences in patient quality of life or stress burden between the treatment strategies, said Dr. Brad S. Kahl of the University of Wisconsin, Madison, on behalf of coinvestigators a briefing in advance of his presentation of the results at a late-breaking abstracts session on Dec. 13.
For the end point of time to first cytotoxic therapy, however, maintenance was significantly better, with 95% of patients not on chemotherapy at 3 years, compared with 86% for the re-treatment strategy (hazard ratio, 2.5; P = .027).
"Both strategies performed extremely well," Dr. Kahl said.
The re-treatment strategy was less costly: Patients in the maintenance arm received a mean of 15.8 total doses of rituximab, compared with a mean 4.5 doses in the re-treatment arm, Dr. Kahl noted. "To get this very small improvement in time to chemotherapy took roughly 4 times more drug in the maintenance arm," he said,
"Given that there was no difference in time to treatment failure, and given the excellent results with re-treatment or time to first chemotherapy, given a slightly better toxicity profile [with re-treatment], given a lack of a quality-of-life benefit for maintenance, and given the resource utilization strategy, the re-treatment strategy would be our recommended strategy when you\'re administering single-agent rituximab in this patient population," he said.
Maintenance does, however, provide a progression-free survival advantage for patients with high tumor burden follicular lymphoma following induction with a combination immunochemotherapy regimen, as shown in the PRIMA trial, in which 2-years of rituximab maintenance was associated with significantly better progression-free survival compared with observation alone (Lancet 2011;377:42-51 [doi:10.1016/S0140-6736(10)62175-7]).
But some patients with low tumor burden may still be anxious about "doing nothing," and for them maintenance is still an appropriate option, said Dr. Ephraim P. Hochberg from the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.
"In my practice, the patients who I think are going to be psychologically intolerant of relapse, or for whom relapse is a devastating personal event, those are patients for whom there is a benefit to maintenance rituximab that\'s not measured in this sort of analysis," he said in an interview. Dr. Hochberg was not involved in RESORT.
The RESORT trial enrolled 545 patients with non-Hodgkin’s lymphoma, 384 of whom (71%) had a follicular histology; patients with nonfollicular histologies are being analyzed separately. Among the 384 patients, 274 had a response to induction rituximab, and were then randomized to either re-treatment at progression (134) or to maintenance with rituximab 375 mg/m2 every 12 weeks. Each strategy was continued until treatment failure.
Time to treatment failure was defined as progression within 6 months of the last rituximab infusion, no response to re-treatment, initiation of alternative therapy, or inability to complete the protocol therapy. Patients were evaluated every 3 months and had restaging CT scans every 6 months,
Grade 3 or 4 hematologic toxicities were seen in less than 5% of patients, and there were two on-study deaths, one in each treatment arm. Both strategies were "extremely well tolerated with minimal toxicities," Dr. Kahl said. There were more toxicities leading to a failure event in the maintenance arm, however.
"Our analysis so far shows that there is no quality-of-life benefit for the maintenance strategy relative to retreatment," he said.
The E4402 (RESORT) trial was sponsored by the Eastern Cooperative Oncology Group and the National Cancer Institute. Dr. Kahl disclosed being a consultant to Genentech and Roche, comarketer of rituximab. Two of his coauthors also are consultants to the company, and one is an employee. Dr. Hochberg has received consulting fees or research support from the company.