Combination Therapy of Nivolumab in First Line and Relapsed/Refractory Classic Hodgkin's Lymphoma: A Systematic Review and Meta-Analysis of Clinical Trials

Introduction

Nivolumab has been FDA approved for the treatment of relapsed/refractory (R/R) classic Hodgkin lymphoma (CHL). A meta-analysis by Amraee et al. in patients of R/R CHL with nivolumab showed pooled overall response rate (ORR) was 68% with complete remission (CR) rate 16.8%. Similarly, a meta-analysis of brentuximab vedotin (BV) in R/R CHL showed pooled ORR of 62.6% (95% CI, 58.5-74.5). Combination of nivolumab with BV is being explored in patients with R/R CHL. Here we provide a comprehensive review of combination treatment of nivolumab with other therapies in R/R CHL.

With the current data in R/R setting current trials have also explored nivolumab in first line treatment of CHL. We also provide a systematic review of the current trials in CHL in first line setting.

Methods

PubMed, Embase, Scopus were searched for all relevant articles from database inception to June 2022. We also reviewed abstracts and presentations from all major conference and reviewed citation lists. Selection criteria included clinical trials using combination treatment of nivolumab with other chemotherapy in CHL. A total of 559 records were screened by title and abstract and 8 records were included for the final analysis. R software was used for statistical analysis.

Results

We found 5 studies of nivolumab with BV, 2 studies of nivolumab with AVD, 1 study each of nivolumab with ibrutinib, ICE, ruloxitinib, bendamustine and ipilimumab (Table 1). For the nivolumab with BTX in R/R CHL the pooled ORR was 84% (95%CI 0.74 -0.91 p <0.01). The pooled CR rate was 62% (95%CI 0.51-0.72 p 0.88). For the nivolumab with BTX in treatment naïve CHL the pooled ORR was 61% (95%CI 0.31 -0.85 p <0.01). The pooled complete response (CR) rate was 47% (95%CI 0.24-0.71 p <0.01). Grade 3 adverse event (AE) rate was 40% (95%CI 0.18-0.67 p<0.01) and treatment discontinuation AE rate is 8% (95%CI 3-17% p 0.22).

Two studies were analyzed in the nivolumab and AVD group in treatment naïve CHL. The pooled overall response rate (ORR) of nivolumab with AVD was 92% (95%CI 0.80 -0.97 p 0.07). The pooled complete response (CR) rate was 76 % (95%CI 0.49-0.68 p 0.28) and grade 3 adverse event (AE) rate was 72% (95%CI 0.58-0.83 p 0.04).

Conclusion

Nivolumab with BV in R/R CHL had better pooled ORR (84% and 92% respectively) when compared with other meta-analysis performed with nivolumab alone (68%) or BV (62.6%) alone. However well-designed randomized controlled trials should be conducted to confirm the findings of this meta-analysis. There is comparable grade 3 or greater AE with nivolumab, BV combination (47% vs 33%) in R/R CHL when compared to ABVD.

No relevant conflicts of interest to declare.