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Pembrolizumab Versus Brentuximab Vedotin in Relapsed/Refractory cHL

December 6, 2021

December 2021

In patients with relapsed/refractory classical Hodgkin lymphoma (cHL), treatment with immunotherapy agent pembrolizumab was associated with greater improvements in health-related quality of life (HRQoL), compared with brentuximab vedotin (BV), according to findings from the KEYNOTE-204 trial published in Blood Advances.

Lead author Pier Luigi Zinzani, MD, PhD, of the University of Bologna in Italy, told ASH Clinical News that the prognosis of patients with relapsed/refractory cHL remains poor, despite available treatment. Additionally, many of the treatments used for this population adversely affect HRQoL, contributing to additional patient burden associated with the disease.

Dr. Zinzani and colleagues noted that while BV has become a standard second-line therapy, research shows long-term declines in HRQoL with this option. In contrast, pembrolizumab may be associated with fewer adverse events compared with BV. Additionally, results from the KEYNOTE-087 trial showed that pembrolizumab led to improvements in or maintenance of patients’ health status, function, and symptoms, all of which are key components of HRQoL.

To compare the HRQoL outcomes of the two treatments in this patient population, the researchers evaluated data from the international phase III KEYNOTE-204 trial, which included patients with cHL who had relapsed or refractory disease after, or were deemed ineligible for, autologous hematopoietic cell transplantation (AHCT). Patients were randomly assigned to receive either pembrolizumab (n=151) or BV (n=153).

In this analysis of the KEYNOTE-204 findings, the investigators obtained data on HRQoL in patients who received one or more doses of the study drug from patient-reported outcomes (PROs). Of these, researchers focused on the EQ-5D and the EORTC QLQ-C30 questionnaires, which were administered every six weeks until week 24, followed by every 12 weeks.

The primary PRO endpoints included the mean score changes in the QLQ-C30 Global Health Status (GHS)/QoL and functioning scale scores as well as EQ-5D VAS and utility scores. The investigators also assessed the proportions of patients who had deteriorated, stable, or improved scores at 24-week follow-up on the QLQ-C30 GHS/QoL and functional scales, which were defined as:

  • deteriorated: ≥10-point score decrease
  • stable: <10-point score change
  • improved: ≥10-point score increase

A total of 146 patients in the pembrolizumab group and 150 patients in the BV arm who received at least one treatment and completed at least one PRO assessment were included in the PRO analysis. The investigators reported high completion rates of the QLQ-30 and EQ-5D questionnaires at baseline (>90%) for both the pembrolizumab and the BV treatment groups. Both treatment groups also had comparable and high compliance rates for QLQ-C30 and EQ-5D at baseline (>90%) and at week 24 (≥80%).

There was a significant improvement from baseline to week 24 on the QLQ-C30 Global Health Status (GHS)/QoL in the pembrolizumab arm and worsening in the BV group (least squares mean difference = 8.60; 95% CI 3.89-13.31; p=0.0004). Additionally, there were improvements for each QLQ-C30 domain, aside from the emotional and cognitive functioning domain, with pembrolizumab.

Treatment with pembrolizumab also prolonged time to deterioration for GHS/QoL compared with BV (hazard ratio = 0.40; 95% CI 0.22-0.74; p=0.003) as well as each QLQ-C30 domain except for the cognitive functioning domain.

According to the investigators, a limitation of this analysis included its open-label design, which the researchers noted could have influenced patient responses. Additionally, the lack of formal hypothesis testing for the HRQoL endpoints represents another potential limitation of this research.

Despite these limitations, the researchers wrote that their findings “suggest that pembrolizumab should be considered the preferred treatment option for patients with relapsed/refractory cHL who have experienced relapse following AHCT or who are ineligible for AHCT.”

Study authors report relationships with Merck, which funded the study.


Zinzani PL, Ramchandren R, Santoro A, et al. Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma [published online ahead of print, 2021 Oct 13]. Blood Adv. doi: 10.1182/bloodadvances.2021004970.


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