Pembrolizumab Shows Superior PFS in Relapsed/Refractory Classical Hodgkin Lymphoma

John Kuruvilla, MD

Treatment with pembrolizumab (Keytruda) induced a 4.9-month progression-free survival (PFS) benefit over brentuximab vedotin (BV) in patients with relapsed/refractory classical Hodgkin lymphoma, according to findings presented at the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

"Pembrolizumab should be considered the preferred treatment option and the new standard of care in relapsed/refractory classical Hodgkin's lymphoma in patients that have relapsed post autologous stem cell transplant or are ineligible for autologous stem cell transplant," said lead author John Kuruvilla, MD, of the Princess Margaret Cancer Centre in Toronto, Canada.

Treatment with pembrolizumab showed an increase in PFS of 4.9 months (13.2 months vs 8.3 months; HR, 0.65; 95% CI, 0.48-0.88; P = 0.00271), and the benefit extended to several key subgroups, including those ineligible for autologous stem cell therapy (auto-SCT; HR, 0.61; 95% CI, 0.42-1.23), those with primary refractory disease (HR, 0.52; 95% CI, 0.33-0.83), and those who were BV-naïve (HR, 0.67; 95% CI, 0.49-0.92).

A total of 304 patients were enrolled in the randomized, open-label, phase III KEYNOTE-204 study, with 151 patients assigned to the pembrolizumab arm and 153 assigned to receive BV. All patients were aged ≥18 years and were either post auto-SCT or ineligible for auto-SCT. Both BV-naïve and BV-exposed patients were eligible for the study.

The primary end point of the study was PFS per blinded independent central review (BICR) per International Working Group criteria including clinical and imaging data after auto-SCT or allogeneic SCT along with overall survival.

The objective response rate was 65.6% for pembrolizumab vs 54.2% for the BV arm, with 24.5% of patients achieving a complete response and 41.1% of patients seeing a partial response to treatment with pembrolizumab. Duration of response also favored the pembrolizumab arm, with an increase of 6.9 months when compared with BV (20.7 months vs 13.8 months). Data cutoff for these results were January 16, 2020.

Safety reports were consistent with the known profiles of each agent. Serious treatment-related adverse events (TRAEs) were slightly higher for patients receiving pembrolizumab, with 16.2% (n = 24) reporting a serious TRAE.

The most commonly reported TRAEs were hypothyroidism (15.5%), pyrexia (12.8%), pruritis (10.8%), and fatigue (8.8%). Nineteen patients (12.8%) discontinued treatment due to TRAEs, compared with 25 (16.4%) in the BV arm. There was one death due to a TRAE with pembrolizumab, resulting from a grade 5 case of pneumonia.

Immune-mediated adverse events (IRAEs) were higher in the pembrolizumab arm, with the most common being hypothyroidism (18.9%) and pneumonitis (10.8%, of which 5.4% were grade 3/4 IRAEs). of the 16 patients who reported pneumonitis, 15 required treatment with corticosteroids, which led to resolution in 12 patients.

Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 8005

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