Blood cancers

Pembrolizumab may be new standard of care in relapsed/refractory Hodgkin lymphoma

Pembrolizumab could be considered a new standard of care for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma who have relapsed post– autologous stem cell transplant or are ineligible for transplant, according researchers commenting on new trial findings presented at the ASCO 2020.

Results from the phase III KEYNOTE-204 trial released as part of the virtual meeting this week showed that pembrolizumab had a significant progression-free survival (PFS) benefit over brentuximab vedotin.

In the international, open-label trial, 300 patients were randomised to either pembrolizumab 200 mg IV brentuximab 1.8 mg/kg IV every three weeks.

After follow up averaging 24 months, significantly greater improvement was seen with in the pembrolizumab arm for the primary endpoint of progression free survival (13.2 months) compared with the BV arm (8.3 months, HR 0.65). The 12 month PFS rates were 53.9% vs 35.6%, respectively, according to lead investigator Professor John Kuruvilla of the Princess Margaret Cancer Centre, Toronto, Canada.

Benefit was observed in all subgroups tested, including patients with no auto-SCT (HR=0.61), primary refractory disease (HR=0.52), prior brentuximab (HR=0.34) and brentuximab-naive (HR=0.67).

Benefits for pembrolizumab were also seen for secondary outcomes such as investigator assessment PFS (median 19.2 vs 8.2 months HR 0.49).

The overall response rate (ORR) was 65.6% for pembrolizumab and 54.2% for brentuximab; Complete response rates were 24.5% and 24.2%, respectively, but these were not significant different.

Median (range) duration of response (DOR) was 20.7 months (0.0+ to 33.2+) for pembrolizumab and 13.8 months (0.0+ to 33.9+) for brentuximab.

Grade 3-5 treatment related adverse events (TRAE)occurred in 19.6% of patients with pembrolizumab and 25.0% with brentuximab. One death due to TRAE occurred with pembrolizumab (pneumonia).

In an ASCO discussion of the results, Dr Mark Roschewski, Clinical Director, Lymphoid Malignancies Branch of the US National Cancer Institute, said the ‘practice defining’ results showed that pembrolizumab was clearly more effective than brentuximab vedotin in this setting and was particularly beneficial for primary refractory patients.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said.

However he cautioned that serious pneumonitis was seen in up to one in twenty patients, and he would therefore reconsider in patients at risk of lung toxicity.

“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 overall survival of these patients, something that would take longer follow up to really get a good handle on.

Dr Mark Roschewski added that a future research question was whether PD-1 inhibitors now represent a preferred strategy to convert patients that are considered ineligible for autologous stem cell transplant to become eligible.

Speaking to the limbic Professor Mark Hertzberg, Director of the Clinical Haematology Service at Prince of Wales Hospital, Sydney said the results were ‘tantalising’ and might tip the balance towards the use of pembrolizumab, although it was too early to say if the study would be immediately practice changing.

“One caveat is that brentuximab vedotin lends itself more to to use in combination with other agents such as bendamustine, so it’s not so clear cut,” he said.

Both brentuximab and prembrolizumab are currently PBS subsidised for patients with relapsed or refractory Hodgkin lymphoma and who have failed autologous stem cell transplant (ASCT) or is ASCT naïve, he noted.

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