In the DAWN trial, however, investigators said, “some patients experienced prolonged remission durations and symptom relief with no new safety signals.”
A phase II trial of single-agent ibrutinib in chemoimmunotherapy-relapsed or -refractory follicular lymphoma (FL) failed to meet its primary endpoint for overall response.
Commenting on their results, Ajay K. Gopal, MD, of the Seattle Cancer Care Alliance, and colleagues, wrote in the Journal of Clinical Oncology that, although the study did not achieve its primary endpoint, the data on the secondary endpoints for duration of response, disease control rate, and lymphoma symptom resolution rate “suggest benefits of this therapy in some patients.”
Bruton tyrosine kinase inhibitors, such as ibrutinib, have shown activity in B-cell malignancies such as chronic lymphocytic leukemia, mantle-cell lymphoma, and marginal-zone lymphoma. On the basis of current research, as well as preliminary data on use of this agent in FL, Gopal and colleagues conducted the DAWN trial to test ibrutinib in chemoimmunotherapy-relapsed or -refractory disease.
DAWN was an open-label study in which ibrutinib at a dosage of 560-mg daily was assigned to 110 patients with FL between March 2013 and May 2016. Patients had already received a median of three prior lines of therapy.
At a median follow-up of approximately 28 months, about 1 in 5 patients had responded. The overall response rate was 20.9% (95% CI, 13.7%−29.7%); this did not meet the lower bound threshold of 18% for the primary endpoint. Twelve patients achieved a complete response (CR). The researchers did not identify any baseline markers predictive of response.
“To account for the possibility of tumor flare or delayed response, 32 patients without clinical signs of progression were permitted to continue receiving ibrutinib after initial radiographic evidence of disease progression,” the researchers wrote. “Among these patients, seven (23%) had independent review committee–confirmed response-four CR and three PR-after remaining on therapy at a median of 22.0 weeks (range, 11.6–59.6 weeks) after starting ibrutinib.”
The median duration of response was 19.4 months, with a median PFS of 4.6 months. The 30-month overall survival was 61%. In addition, 67% of patients reported resolution of lymphoma symptoms.
Gopal and colleagues commented that, in patients who responded to treatment, regulatory T cells were downregulated at C3D1 (P = .02), and there was an increase in levels of the Th1-promoting (antitumor) cytokines interferon-Î³ and interleukin-12 (P ≤ .035).
The most commonly occurring adverse events were diarrhea, fatigue, cough, and muscle spasms. About half of patients reported serious adverse events.
“The results of this study do not support ibrutinib monotherapy for patients with relapsed/refractory follicular lymphoma; however, some patients experienced prolonged remission durations and symptom relief with no new safety signals,” the researchers wrote. “The relative clinical benefit of ibrutinib in follicular lymphoma will be further defined in ongoing phase III trials of chemoimmunotherapy with or without ibrutinib in the relapsed/refractory setting and rituximab-ibrutinib versus rituximab monotherapy in treatment-naive patients with follicular lymphoma.”