Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma

Abstract

Objectives Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure. Methods This study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET-CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03. Results Median follow-up was 19 (9-47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50-93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12-53%). Any grade AEs were observed in 12 patients (63%), 3-4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5-21) months. Conclusions Combination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach.

Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up

“…In the CheckMate 205 study, nivolumab showed efficacy in patients with R/R cHL who had previously been treated with BV, 10 and a retrospective analysis of patients with R/R cHL treated with nivolumab plus BV indicated promising efficacy. 30 R/R PMBL shares clinical and molecular features with R/R cHL, including high mutational density and expression of CD30, 13 , 14 , 15 , 31 and data reported here for CheckMate 436 possibly indicate a similar synergy in patients with R/R PMBL.…”

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

“…While 90% of the patients with HL can be cured by standard first-line treatment, 10%–30% of patients show relapse or refractory disease after the standard first-line treatment. 4 , 7 Younger patients tend to be healthier, and therefore, can often tolerate higher-intensity chemotherapy and AHCT. Thus, AHCT was reported to afford a better prognosis and adopted as the standard treatment for R/R patients, according to the guidelines.…”

“…Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for patients with refractory or relapsed (R/R) disease, resulting in response rates higher than 50%. 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 These new agents have been subsequently included in earlier lines of therapy, including pre-AHCT salvage, post-AHCT consolidation, and first-line treatments. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 This change in practice means that patients with single- or double-refractory (refractory to BV and/or ICIs) disease are becoming a common clinical problem.…”

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma

“…BV has produced promising results even when given as a single agent in the treatment of R/R cHL (overall response rates [ORR], 57%-75% alone or with nivolumab 11 , 12 , 13 , 14 , 15 ), R/R CD30+ non-Hodgkin lymphomas (ORR, 36%-44%; complete response rate [CRR], 17%-24%), 4 , 5 and R/R ALCL (ORR, 67%-86%; CRR, 56%-66%). 12 , 16 Although designed to target CD30, the efficacy of BV has also been shown in lymphomas with variable 5 , 6 or absent 17 , 18 CD30 expression, such as non-Hodgkin B-cell lymphoma or non-ALCL T-cell lymphomas.…”