Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study

Abstract

Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) in whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase II CheckMate 205 trial. We present updated results (median follow-up ~5 years). Patients with R/R cHL, who were brentuximab vedotin (BV)-naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C), were administered nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. Patients in cohort C with complete remission (CR) for 1 year could discontinue nivolumab and resume upon relapse. Among 243 patients (cohort A, n = 63; B, n = 80; C, n = 100), objective response rate (ORR) was 71.2% (95% CI, 65.1-76.8); CR rate was 21.4% (95% CI, 16.4-27.1). Median duration of response, CR, and partial remission were 18.2 (95% CI, 14.7-26.1), 30.3, and 13.5 months, respectively. Median progression-free survival was 15.1 months (95% CI, 11.3-18.5). Median overall survival (OS) was not reached; OS at 5 years was 71.4% (95% CI, 64.8-77.1). In cohort C, all 3 patients who discontinued in CR and were subsequently re-treated achieved objective response. No new or unexpected safety signals were identified. This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT failure. Results suggest patients may discontinue treatment after persistent CR and reinitiate upon progression. This trial is registered on clinicaltrials.gov as NCT02181713.

Immune checkpoint inhibitors in advanced and relapsed/refractory Hodgkin lymphoma: current applications and future prospects

“…For patients who are ineligible for ABVD or BV-AVD because of frailty or age, the Niviniho and ACCRU trials investigated alternative ICI-based regimens. Both studies had non-durable responses with median PFS of 9 months with nivolumab plus vinblastine augmentation and 18 months with BV-nivolumab, respectively ( Table 2 ) ( 40 , 41 ). These responses were similar to those seen with nivolumab and pembrolizumab monotherapy ( 42 , 43 ).…”

Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice

“…The long-term followup analysis of the study showed durable responses with a median DOR of 18.2 months overall (33.3 months for patients achieving CR) and a 5-year overall survival (OS) of 71.4%. Interestingly, a small portion of patients who discontinued nivolumab in CR and later relapsed obtained a second response after treatment rechallenge [45]. In the CheckMate 744 phase II trial, nivolumab has also been tested as a salvage treatment for young R/R cHL patients in combination with BV +/− bendamustine in a response-adapted approach.…”

Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV‐independent major determinant of microenvironment composition in classic Hodgkin lymphoma

“… 13 , 14 While single‐agent anti‐PD1 therapy is standard‐of‐care in relapsed or refractory HL, it rarely leads to cure in this setting. 15 , 16 Current therapeutic strategies in HL hence combine anti‐PD1 ICB with cytotoxic therapy in the first‐line setting and with other therapeutic modalities in the relapsed situation. 17 , 18 To fully leverage the potential of ICB in HL, understanding the interaction of HRSCs with T cells in the TME seems crucial.…”