HL-032: Nivolumab and Brentuximab Vedotin (BV)–Based, Response-Adapted Treatment in Children, Adolescents, and Young Adults (CAYA) With Standard-Risk Relapsed/Refractory Classical Hodgkin Lymphoma (R/R cHL): Primary Analysis of the Standard-Risk Cohort of the Phase 2 CheckMate 744 Study

Abstract

Background Outcomes for younger patients with R/R cHL are poor, particularly for those without complete metabolic response (CMR) before autologous transplant (auto-HCT). CheckMate 744 ( NCT02927769 ) is an ongoing phase 2 study for CAYA with R/R cHL, evaluating a risk-stratified, response-adapted approach using nivolumab plus BV, and for patients without CMR, BV plus bendamustine. In the initial analysis of the standard-risk cohort (R2), the regimen was well tolerated with high CMR rates before consolidation with high-dose chemotherapy plus auto-HCT. We report primary analysis data. Patients 5–30 years old; had first-line treatment without auto-HCT. Design Risk stratification has been described (Harker-Murray, ASH 2018). Patients received 4 induction cycles of nivolumab plus BV; patients without CMR by blinded independent central review (BICR) received BV plus bendamustine intensification. Patients with CMR at any time could proceed to consolidation off study. Response was per Lugano 2014 criteria. Primary endpoint: CMR rate (Deauville ≤3) per BICR any time before consolidation. Results 44 patients were treated in R2 (median follow-up: 20.9 months); 43 received 4 induction cycles and 11 received intensification. Median age was 16 years (range, 9–30); 24 (55%) patients had primary refractory cHL. CMR rate (90% CI) any time before consolidation was 88% (77–95) and 89% (78–95) per BICR and investigator, respectively; objective response rate (ORR) was 98% by either assessment. After 4 cycles of induction, CMR was 59% and 66% per BICR and investigator, respectively; ORR (90% CI) was 82% (70–91) and 89% (78–95), respectively. One-year progression-free survival rate by BICR was 91% (90% CI, 77–96). During induction, 8 patients (18%) experienced grade (G) 3–4 treatment-related adverse events (TRAEs); the most common any-grade TRAEs were nausea and hypersensitivity (20% each). One TRAE led to discontinuation (G3 anaphylaxis). Most treatment-related immune-mediated AEs were G1–2 (1 patient had 2 G3 infusion-related reactions). Conclusions This risk-stratified, response-adapted approach offers a well-tolerated salvage strategy with high CMR rates and no new safety signals for CAYA with R/R cHL. Most patients avoided bendamustine prior to consolidation. Further follow-up may confirm durability of disease control. Funding BMS. Previous presentation ASCO 2020