Clinical trialPhase 3Lymphoma

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study

Lancet Oncol · 2021304 patients (pembrolizumab: 151, brentuximab vedotin: 153)

Kuruvilla J, Ramchandren R, Santoro A, et al. Lancet Oncol. 2021. 22:512-524

Study type: Clinical trial
Study name: KEYNOTE-204
Phase: Phase 3
Design: Randomised (1:1), open-label, multicentre trial at 78 hospitals and cancer centres in 20 countries and regions; second interim analysis
Sample size: 304 patients (pembrolizumab: 151, brentuximab vedotin: 153)
Source: Lancet Oncol · 2021
Trial registration: NCT02684292

In plain words

Hodgkin lymphoma is usually well controlled by the first treatment, but in some patients it comes back or does not respond. This study compared two newer drugs in patients whose disease had come back after a stem cell transplant or who could not have a transplant: pembrolizumab (an immunotherapy drug that switches on the immune system against the cancer) and brentuximab vedotin. With pembrolizumab, the disease stayed under control for about 13 months on average, compared with about 8 months with brentuximab. The side effects of the two drugs were different: lung inflammation was seen more often with pembrolizumab, and low white blood cell counts and nerve damage in the hands and feet more often with brentuximab.

Key results

13.2 months vs 8.3 months

Median progression-free survival

HR 0.65 (95% CI 0.48–0.88); p = 0.0027; median time to data cut-off 25.7 months

16% vs 11%

Serious treatment-related adverse events

24 of 148 vs 16 of 152 patients

Not analysed

Overall survival

Not assessed in this interim analysis

Drugs in this study:Pembrolizumab (Keytruda)

Dose and schedule cards

Pembrolizumab (KEYNOTE-204 trial)

Relapsed or refractory classic Hodgkin lymphoma in adults (ECOG 0–1) who have relapsed after autologous stem cell transplantation or are not transplant candidatesOn the page “Lymphoma” · Treatment regimens and dosing: Hodgkin lymphoma

Relapsed or refractory classic Hodgkin lymphoma in adults (ECOG 0–1) who have relapsed after autologous stem cell transplantation or are not transplant candidates

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg every 3 weeks or 400 mg every 6 weeks (children: 2 mg/kg, maximum 200 mg, every 3 weeks)	IV	Day 1

Cycle length: Every 3 weeks (or every 6 weeks)
Duration: Until disease progression, unacceptable toxicity or a maximum of 24 months

In KEYNOTE-204, pembrolizumab 200 mg every 3 weeks was compared with brentuximab vedotin 1.8 mg/kg every 3 weeks; treatment duration and the alternative dose from the FDA label. Check liver enzymes, creatinine and thyroid function at baseline and periodically; for grade 4 haematologic toxicity in Hodgkin lymphoma, withhold the drug until recovery to grade 0–1. For transplant-eligible patients, the EHA guideline recommends checkpoint inhibitor–containing salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation.

On the page “Lymphoma” · Treatment regimens and dosing: Hodgkin lymphoma

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Pembrolizumab

Pembrolizumab 200 mg IV every 3 weeks.

2Brentuximab vedotin

Brentuximab vedotin 1.8 mg/kg IV every 3 weeks.

Source of the regimen details: Abstract of the paper on PubMed

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 years and older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and ECOG performance status 0 or 1, who were ineligible for autologous haematopoietic stem cell transplantation (HSCT) or had relapsed after it.

Endpoints

Dual primary endpoints: progression-free survival by blinded independent central review, and overall survival (not assessed in this interim analysis).

Safety: in all patients who received at least one dose of study drug.

Safety and side effects

Most common treatment-related grade 3 to 5 adverse events (pembrolizumab versus brentuximab vedotin): pneumonitis 4% versus 1%, neutropenia 2% versus 7%, decreased neutrophil count 1% versus 5% and peripheral neuropathy 1% versus 3%. Serious treatment-related adverse events occurred in 16% versus 11% of patients. One treatment-related death from pneumonia was reported in the pembrolizumab group.

Clinical significance and place in guidelines

KEYNOTE-204 is the first randomised phase 3 comparison of a PD-1 inhibitor with brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma. The significant improvement in progression-free survival led the authors to regard pembrolizumab as the preferred option for patients who have relapsed after autologous transplantation or are ineligible for it.

Limitations

The study was open-label and this report is an interim analysis. Overall survival (a dual primary endpoint) was not assessed in this analysis. Pneumonitis and one death from pneumonia in the pembrolizumab group need attention.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.