Nivolumab/brentuximab vedotin in R/R HL: good CMR rates

Early data featured high rates of complete metabolic response (CMR) before consolidation with high-dose chemotherapy (HDCT)/auto-HCT in the standard-risk patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL).

Prof. Christine Mauz-Körholz (Justus-Liebig-Universität Gießen, Germany) presented the results of the Checkmate 744 trial [1], which tested a new therapy in children, adolescents, and young adults 5-30 years old (CAYA) with relapsed/refractory classical Hodgkin lymphoma (R/R cHL), particularly those who do not achieve complete metabolic response (CMR) before autologous haematopoietic cell transplantation (auto-HCT). First salvage therapy with nivolumab + brentuximab vedotin (BV) has shown a CMR rate of 67% and a 2-year progression-free survival (PFS) rate of 79% in adults with R/R cHL, but it is unknown how this translates to CAYA. CheckMate 744 is an ongoing phase 2 study for CAYA with R/R cHL (at least prior anti-cancer therapy that did not work, including autologous stem cell transplant), using a risk-stratified, response-adapted approach with nivolumab + BV followed by BV + bendamustine for patients with a suboptimal response.

Standard-risk patients (n=44, median age 16 years, with 71% <18 years old) received 4 cycles of induction with nivolumab + BV; those without CMR by blinded independent central review (BICR) received BV + bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (HDCT/auto-HCT). The primary endpoint was CMR rate (Deauville ≤3) at any time before consolidation, as determined by the BICR.

With a median follow-up of 20.9 months, 43 patients had received 4 induction cycles and 11 received intensification, 9 of whom proceeded to consolidation per protocol. CMR rate by BICR any time before consolidation was 88% (90% CI, 77-95; Table). CMR rate and ORR by BICR after induction were 59% and 82%, respectively (Table). 9 of the 11 (82%) patients who received intensification achieved CMR. Progression-free survival at 1 year was 91% (90% CI 77–96).

Table: CMR and ORR per BICR and investigator in response-evaluated patients



During induction, 70% patients had any-grade treatment-related adverse events (TRAEs); 18% were grade 3-4. The most common any-grade TRAEs were nausea and hypersensitivity (20% each). There was 1 TRAE (grade 3 anaphylaxis) leading to discontinuation. Treatment-related immune-mediated AEs were mostly grade 1–2, except for 1 patient who had 2 grade 3 infusion-related reactions.

In conclusion, this nivolumab and BV-based, risk-stratified, response-adapted salvage strategy had high CMR rates and was well tolerated with no new safety signals in CAYA with R/R cHL. Most patients did not require bendamustine intensification. Durability of disease control will require further studies.

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   1. Mauz-Körholz C, et al. Response-adapted therapy with nivolumab + brentuximab vedotin in children, adolescents, and young adults with SD-risk R/R classical HL. EHA25 Virtual, 11-21 June 2020, Abstract S224.

Posted on 28 August, 202019 November, 2021