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Nivolumab (Opdivo) monotherapy led to complete remissions in over 50% of patients with early-stage unfavorable classic Hodgkin's lymphoma, and combined with doxorubicin, vinblastine, and dacarbazine (AVD) yielded responses in nearly all, results of a phase II study showed.

In the randomized NIVAHL trial, interim restaging after four doses of nivolumab alone showed that 96% achieved an objective response, with complete responses in 51%, reported Andreas Engert, MD, of University Hospital of Cologne, Germany, and colleagues.

And interim restaging for patients assigned to two cycles of nivolumab plus AVD showed that 100% achieved an objective response, including a complete response in 87%, the group wrote in .

The primary endpoint of the study was complete response rate after end of study treatment. Among the 101 patients eligible for this analysis, the complete response rate was 90% (95% CI 79%-97%) among those who received concomitant nivolumab plus AVD, and 94% (95% CI 84%-99%) among those who received sequential treatment.

"We conclude very good efficacy of both treatment strategies despite marginally missing the primary end point in the concomitant therapy group," Engert and colleagues wrote. The benchmark for efficacy was set at 80%.

With a median follow-up of 13 months, 12-month progression-free survival was 100% for concomitant treatment and 98% for sequential treatment; 12-month overall survival was 100% in both groups.

In recent years, research has shown that among subtypes of lymphoma, classic Hodgkin's lymphoma is the most sensitive to the use of checkpoint inhibitors, according to Barbara Pro, MD, of Robert H. Lurie Cancer Center and Northwestern University-Feinberg School of Medicine in Chicago.

"In the relapsed/refractory setting, checkpoint inhibition has shown significant remission rates with long-term remissions," said Pro, adding that the complete response rates in this advanced setting are not as high as those found in the NIVAHL study.

"A longer follow-up is needed to see the real impact on progression-free and overall survival in these patients with unfavorable early-stage [Hodgkin's lymphoma]," Pro noted. "Future studies should look at the possibility of reducing the number of chemotherapy cycles for patients who received complete response after monotherapy with nivolumab and investigate the role of radiation for patients who achieved complete response."

From April 2017 to October 2018, 109 patients were randomly assigned to concomitant treatment with 4 cycles of nivolumab plus AVD or sequential treatment with four doses of nivolumab, two cycles of nivolumab plus AVD, and then two cycles of AVD at standard doses. All patients then underwent radiotherapy with 30-Gy at the involved site.

Grade 3 or higher treatment-related adverse events were reported in 76% of patients in the concomitant group and 80% of patients in the sequential group. Serious adverse events occurred in 38% and 28% of the two groups, respectively. Seven cases of hypothyroidism of grade 2 or lower, one case of grade 2 intermittent pneumonitis, and one case of grade 1 intermittent colitis were reported. According to the researchers, these early immune-related adverse events may be "potentially due to preserved immunocompetence in treatment-naive patients."

To mitigate high-grade early-onset immune-related adverse events, the study protocol was amended to add mandatory dexamethasone-based prophylaxis. After this, no measurable differences in the occurrence of adverse events were noted between the two arms.

"Longer follow-up is also needed to see what the real toxicity of these regimens are," Pro said. "It looks feasible though and appears to be very well tolerated, at least from this preliminary data analysis."

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