ASCO 2020-PEMBROLIZUMAB FOR HODGKIN LYMPHOMA

Pembrolizumab monotherapy demonstrated a progression-free survival (PFS) benefit over brentuximab vedotin (BV) in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma, according to the results from the phase III international KEYNOTE-204 trial (Abstract 8005). Clinically meaningful improvement in PFS was observed in all subgroups tested, including patients who did not receive an autologous stem cell transplant (auto-SCT), those with primary refractory disease, those who were BV-naive, and patients previously treated with BV.

John Kuruvilla, MD, FRCPC, of the Princess Margaret Cancer Centre, Toronto, Canada, presented the study findings during the ASCO20 Virtual Scientific Program.

Dr. Mark Roschewski

“Salvage chemotherapy and auto-SCT is the standard of care for eligible patients with R/R classical Hodgkin lymphoma,” he said. “Unfortunately, there is no standard of care for patients ineligible for auto-SCT due to chemo-refractory disease, comorbidity, or advanced stage.”

In explaining the rationale behind KEYNOTE-204, Dr. Kuruvilla noted that BV is the standard of care for patients who have relapsed post–auto-SCT and is now increasingly used in curative settings.

The trial compared pembrolizumab monotherapy and BV in 304 patients who were post–auto-SCT or ineligible for auto-SCT and had measurable disease and an ECOG Performance Status of 0 or 1. Patients were randomly assigned 1:1 to 200 mg of intravenous pembrolizumab once every 3 weeks or 1.8 mg/kg of intravenous BV once every 3 weeks and stratified according to status after first-line therapy and whether or not they had received prior auto-SCT. Primary endpoints were PFS per blinded independent central review and overall survival (OS); secondary endpoints included PFS per investigator review, objective response rate (ORR), and safety.

The median PFS was 13.2 months in the pembrolizumab arm compared with 8.3 months in the BV arm (HR 0.65, 95% CI [0.48, 0.88]; p = 0.00271).

“More durable responses and higher response rates were associated with pembrolizumab versus BV, although this was not statistically significant,” Dr. Kuruvilla said.

“More durable responses and higher response rates were associated with pembrolizumab versus BV, although this was not statistically significant,” Dr. Kuruvilla said.

The ORR was 65.6% versus 54.2%, and the duration of response was 20.7 versus 13.8 months in the pembrolizumab and BV arms, respectively.

In discussing the safety profiles of the two treatment arms, Dr. Kuruvilla noted that the rates of treatment-related adverse events (TRAEs) were similar; grade 3 to 5 TRAEs occurred in 19.6% of patients treated with pembrolizumab versus 25.0% of patients treated with BV.

“Serious TRAEs were numerically more frequent in the pembrolizumab arm at 16.2% versus 10.5%,” he said. “There was one treatment-related death in the pembrolizumab arm—this was a case of grade 5 pneumonia.” In the pembrolizumab arm, 8.8% of patients discontinued treatment due to serious TRAEs compared with 3.9% of patients in the BV arm.

Dr. Kuruvilla concluded that “pembrolizumab should be considered the preferred treatment option and a new standard of care for the treatment of R/R classical Hodgkin lymphoma in patients who have relapsed post–auto-SCT or are ineligible for auto-SCT.”

Mark Roschewski, MD, of the National Cancer Institute, was the discussant for the abstract. He said that pembrolizumab was clearly more effective than BV in the investigated setting, with a clinically meaningful PFS benefit PFS of over 4 months.

“I was also encouraged to see that the benefit was particularly pronounced in patients who have primary refractory disease,” which is a group of patients who pose a specific clinical challenge, he said.

Although Dr. Roschewski agreed that the study findings were practice-defining, he noted that there are several reasons to be cautious, including the fact that approximately 5% of patients reported grade 3/4 pneumonitis.

“I would also have to say that it’s unknown if this strategy as monotherapy is curative, and we still don’t know if it actually improves the OS for these patients, something that would take longer follow-up to really get a good handle on,” he concluded.

— Jasenka Piljac Žegarac, PhD