Sargramostim (Leukine) paired with a patient-specific immunotherapy mitumprotimut-T (Specifid), failed to reduce time to remission in patients with CD20+ follicular lymphoma following therapy with rituximab (Rituxan), according to the highly anticipated results of a phase III clinical trial.
SAN FRANCISCO -- Sargramostim (Leukine) paired with a patient-specific immunotherapy mitumprotimut-T (Specifid), failed to reduce time to remission in patients with CD20+ follicular lymphoma following therapy with rituximab (Rituxan), according to the highly anticipated results of a phase III clinical trial.
"It's very frustrating," said lead investigator Paul Hamlin, Jr., MD, of Memorial Sloan-Kettering Cancer Center in New York. "This study was a culmination of a decade of work. And right now it looks like we're going back to the drawing board to figure out how to best harness the immune response with this drug."
A phase II trial of follicular lymphoma patients with treatment-nave and relapsed and refractory disease given mitumprotimut-T after therapy with rituximab resulted in an event-free survival plateau at four years, suggesting significant vaccine activity, Dr. Hamlin said.
In the trial, 349 patients with treatment-nave or relapsed/refractory CD20+ follicular lymphoma were randomized to treatment with mitumprotimut-T and sargramostim or placebo and sargramostim after treatment with rituximab at 375 mg/m2 weekly for four weeks (abstract 236).
Enrollees had achieved a complete response (CR), partial response (PR), or stable disease at week 11 after therapy with the rituximab. Sargramostim was given at a dose of 250 mcg subcutaneously daily on days 1 through 4, and mitumprotimut-T was given at 1 mg on day 1 and then monthly for six months, then every other month for six months, and then every three months until disease progression.
The median age of patients in the experimental group was 55 years; the median age in the control group was 53 years. Most patients in both groups in the study had advanced disease. Eighty-nine percent of patients in the experimental group and 83% in the placebo group had stage III or IV disease. There was, however, a significant imbalance in FLIPI score between groups. The experimental group contained significantly more patients with high-risk FLIPI and fewer patient with low-risk FLIPI (p = 0.0042).
The end results showed that outcomes from placebo treatment were actually superior to those from the study drug. Overall time-to-progression was significantly longer in the placebo arm (12.6 months) versus the experimental group (nine months). Even when the investigators adjusted for FLIPI risk group, there was no significant difference in the time-to-progression for patients on the study treatment versus the placebo. There was also no significant difference between groups in overall response rate.
The study drug was well tolerated. The most common adverse event was injection site reaction, which occurred in 93% of patients. Most of these reactions were either mild or moderate.
How do the investigators account for the lack of efficacy seen with mitumprotimut-T? Dr. Hamlin noted that it is possible that the immunosuppressive action of rituximab could have affected patient response to the study drug.
"It's also possible that the idiotype is a weak immunogen or it's an irrelevant target," he said. "The patients' tumor burden may also have played a role in their immune response."