Brentuximab vedotin and nivolumab in combination with chemotherapy for nonbulky, early-stage classical Hodgkin lymphoma

Brentuximab vedotin 和 nivolumab 联合化疗治疗非肿块型早期经典霍奇金淋巴瘤

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Abstract

Most patients with early-stage classical Hodgkin lymphoma (cHL) are treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without radiation therapy, although studies are now evaluating the incorporation of novel agents paired with abbreviated chemotherapy. We present the efficacy and safety of AN+AD (brentuximab vedotin [BV] and nivolumab in combination with doxorubicin and dacarbazine) in patients with early-stage cHL. In this phase 2 study, patients with nonbulky (<10 cm) Ann Arbor stage I or II cHL received 4 cycles of AN+AD. The primary end point was complete response (CR) rate at end of treatment (EOT) by investigator. At the time of this analysis, 154 patients received ≥1 dose of AN+AD. The objective response rate at EOT was 96% (95% confidence interval [CI], 91.7-98.6), and the CR rate was 92% (95% CI, 86.0-95.4). In the favorable (n = 56) and unfavorable (n = 97) subgroups, CR rates were 95% (95% CI, 85.1-98.9) and 91% (95% CI, 83.1-95.7), respectively. The proportion of patients with duration of CR of at least 2 years was 96% (95% CI, 90.9-98.4). At a median follow-up of 27.9 months, the estimated 2-year progression-free survival rate was 97% (95% CI, 92.0-98.8). Any-grade and grade ≥3 treatment-emergent adverse events occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Any-grade treatment-emergent immune-mediated adverse events occurred in 22% of patients. One disease-related death was reported after the safety reporting period. Results from this study support the use of BV and nivolumab in combination with limited chemotherapy for patients with nonbulky, early-stage cHL. This trial was registered at www.clinicaltrials.gov as NCT03646123.

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