Meta-analysis of nivolumab outcomes in Hodgkin lymphoma patients

On 9 February 2019, Azadeh Armaee from the Iran University of Medical Sciences, Tehran, IR, and colleagues, published in Clinical and Translational Oncology a meta-analysis of seven clinical trials in order to investigate the efficacy of nivolumab on classical Hodgkin lymphoma (cHL) patients. 

In this meta-analysis (CRD42018105712), data from seven studies were pooled to assess cHL patient outcomes following treatment with the PD1 inhibitor, nivolumab. The primary aim of this analysis was to calculate the overall objective response rate and survival rate of cHL patients on nivolumab.

Meta-analysis design 

• Current systematic review of online databases with the use of the MeSH terms: ‘checkpoint inhibitor', 'nivolumab',  'Hodgkin lymphoma', and 'PD1 blockade'
• Final included studies (n = 7):
  • Ansell et al. (2015) NEJM
  • Maruyama et al. (2017) Cancer Sci.
  • Younes et al. (2016) Lancet Oncol.
  • Beköz et al. (2017) Ann Oncol.
  • Kasamon et al. (2017) Oncologist
  • Armand et al. (2018) J Clin Oncol. (CheckMate 205)
  • Herbaux et al. (2017) Blood
• Bias was controlled with the use of Cochrane checklists by two independent external observers
• A total of 560 HL patients were included in all seven studies
• No comparator studies for nivolumab with other drugs were included in this analysis
• Most patients received 3 mg/kg of nivolumab every two weeks until response, disease progression (PD) or unacceptable toxicity
• Range of time of nivolumab drug response from all studies: 2.1−8.7 months
• Overall response rate (ORR) range from all studies: 64−95% (all > 50%)
• Progression-free survival (PFS) range from all studies: 58.25−86%
• Since there was no evidence of heterogeneity between studies, the fixed-effects model was used to pool the data

Key findings

• Pooled data from all seven studies revealed:
  • Objective response rate: 68% (95% CI, 64.1−1%; heterogeneity [I²] = 40.19%; P = 0.123)
  • Partial remission: 52% (95% CI, 46.5−57.6%; I² = 28.35%; P = 0.212)
• Sensitivity analysis and forest plots led to the exclusion of the Herbaux et al. (2017) study due to a higher heterogeneity from the rest of the studies (15%; I² = 50.45%; P = 0.073)
• Pooled data from all six studies (excluding Herbaux et al. 2017) revealed:
  • Stable disease: 19% (95% CI, 16−23%; I² = 30%; P = 0.209; fixed-effect model)
• Common adverse events (AEs) following nivolumab were (N, number of evaluated studies):
  • Pyrexia (in N = 3)
  • Rash (in N = 2)
  • Fatigue (in N = 2)
  • Infusion (in N = 2)
  • Hypothyroidism (in N = 1)
  • Neutropenia (in N = 1)
  • Fever (in N = 1)
  • Increased lipase concentrations (in N = 1) 

Conclusions

The results of this meta-analysis indicated that nivolumab, a PD-1 inhibitor, shows promising efficacy in relapsed or refractory cHL patients. Moreover, nivolumab-related AEs were manageable in most cases. The authors mentioned that among the limitations of this study is that fact that most evaluated studies were cohort trials with only a few having a control arm.