A study presented at ASH 2013 in New Orleans examined the role of rituximab in maintenance therapy in patients with follicular lymphoma. The study showed that the drug, when applied long-term, not only significantly prolongs event-free survival, but also more than doubles progression-free survival.
According to Christian J. Taverna, MD, of Münsterlingen Cantonal Hospital, it is clear that while rituximab is effective in maintenance therapy for follicular lymphoma, the optimal duration of treatment has not yet been conclusively determined. To investigate this, the randomized phase III SAKK35/03 trial [1] was conducted. Dr. Taverna now presented the associated results at the ASH Congress in New Orleans.
Short versus long maintenance therapy
“In our study, we compared a short maintenance treatment with rituximab with one for a maximum of five years,” Dr. Taverna said. Specifically, a total of 270 patients with an average age of 57 years were treated with four weekly doses of 375 mg/m2 rituximab. These included patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma. If they responded to induction therapy with a partial or complete response, they continued to receive rituximab at the same dose as maintenance. Two groups were randomized from the remaining 165 patients, 124 of whom were chemotherapy-naive (no chemotherapy to date), at this time:
Arm A: 82 patients with short maintenance (four doses every two months).
Arm B: 83 patients with extended maintenance (for a maximum of five years, until disease progression or the onset of severe toxicities).
The primary endpoint was event-free survival since randomization. Secondary endpoints were progression-free survival, overall survival, and objective response.
Primary endpoint missed – or not?
The median event-free survival was 3.4 years in arm A and 5.3 years in arm B. Consequently, the difference is not statistically significant (p=0.14).
There was a difference in disease progression and recurrence that was difficult to explain during the first eight months after randomization. Since the treatment of the two groups was exactly the same during this period, 375 mg/m2 every two months, this difference cannot be interpreted on the basis of rituximab administration. “On the other hand, when looking only at event-free survival after these eight months, arm B showed a significantly better value than arm A this time, 7.1 years instead of 2.9 years (p=0.004),” Dr. Taverna explained.
Prolonged progression-free survival
Median progression-free survival is significantly longer in Arm B than in Arm A. Specifically, the time to progression can be delayed by 3.9 years with rituximab in long-term maintenance: 7.4 (arm B) vs. 3.5 years (arm A).
“Where we did not see a statistically relevant difference, however, was in overall survival or best response. Only just three patients had to discontinue treatment in arm B due to unacceptable toxicities. This did not apply to anyone in the short-term maintenance therapy group. While there was also only one severe infection (grade ≥3), seven occurred in five patients in arm B,” Dr. Taverna concluded. “Overall, then, it can be said that rituximab in long-term maintenance monotherapy of follicular lymphoma yields good results. It leads not only to a prolongation of event-free survival but also to a doubling of median progression-free survival compared with the eight-month variant, without entailing excessive toxicities.”
Source: 55th ASH Annual Meeting, December 7-10, 2013, New Orleans.
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Taverna CJ, et al: Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. ASH Abstract #508.
InFo ONCOLOGY & HEMATOLOGY 2014; 2(2): 30-31.
CONGRESS Special 2014; 5(2): 3-4
