First-line nivolumab-AVD improves PFS both in adult and paediatric patients with advanced Hodgkin lymphoma

Results from the phase 3 SWOG S1826 trial showed that nivolumab-AVD improved progression-free survival (PFS) compared with brentuximab vedotin-AVD, both in paediatric and adult patients. This is a key step towards harmonising paediatric and adult therapy of Hodgkin lymphoma.

The anti-CD30 antibody drug conjugate brentuximab vedotin (Bv) is standard-of-care in frontline treatment of advanced-stage Hodgkin lymphoma both in paediatric and adult patients, although with a different chemotherapy backbone (AVE-PC vs AVD) [1,2]. However, relapses are still common (7–20%), most paediatric patients still receive consolidating radiotherapy, and in particular paediatric patients are vulnerable to late morbidity.

Recently, nivolumab has shown to be highly effective in relapsed or refractory Hodgkin lymphoma and was well tolerated [3]. Therefore, the SWOG S1826 trial (NCT03907488) compared the efficacy and safety of first-line treatment with nivolumab-AVD and Bv-AVD, both in paediatric and adult patients. The primary endpoint was PFS. Prof. Alex Herrera (City of Hope Medical Center, CA, USA) presented the results [4].

A total of 940 participants (n=237; ≤18 years) with newly diagnosed stage III/IV Hodgkin lymphoma were randomised 1:1 to receive 6 cycles of nivolumab-AVD or 6 cycles of Bv-AVD. In the nivolumab-AVD arm G-CSF was optional, and in the Bv-AVD arm G-CSF was required.

Nivolumab-AVD improved PFS compared with Bv-AVD. At 1-year, PFS rate was 94% compared with 86% in the nivolumab-AVD and Bv-AVD arm, respectively (HR=0.48; P=0.0005). The PFS benefit was observed within all prespecified subgroups (see Figure). In addition, nivolumab-AVD favoured event-free survival (EFS): 1-year EFS rate was 91% compared with 84%, respectively (HR 0.56; P=0.0019). Overall survival data are not yet mature. Less than 1% of patients receive consolidating radiotherapy.

Figure: PFS benefit consisted across prespecified subgroups in SWOG S1826 [1]



AVD, doxorubicin, vinblastine, and dacarbazine; BV, brentuximab vedotin; N, nivolumab; CI, confidence interval; HR, hazard ratio; IPS, international prognostic score.

Nivolumab-AVD was well-tolerated. Although 55% of patients developed neutropaenia, no increased infectious toxicity was observed in the nivolumab-AVD arm compared with the Bv-AVD arm.

“Nivolumab-AVD improves PFS compared with Bv-AVD both in paediatric and adult patients. The low rate of consolidating radiotherapy may reduce late toxic effect of the treatment,” Prof. Herrera concluded. “In addition, this is a key step towards harmonising paediatric and adult therapy of Hodgkin lymphoma.”

1. Ansell SM, et al. N Engl J Med 2022;387:310–320.
2. Castellino SM, et al. N Eng J Med 2022;387:1649–1660.
3. Armand P, et al. J Clin Oncol 2018;36(14):1428–1439.
4. Herrera AF, et al. SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL). Abstract LBA4, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 1 August, 20231 August, 2023