ASCO Annual Meeting
ASCO Annual Meeting
Perspective from Lee Greenberger, PhD
Perspective from Joshua Brody, MD, PhD
Source/Disclosures
Source:

Kuruvilla J, et al. Abstract 8005. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.


Disclosures: Merck Sharp & Dohme funded this study. Kuruvilla reports research funding from, honoraria from or consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Karyopharm Therapeutics, Merck, Novartis, Pfizer, Roche and Seattle Genetics. Please see the abstract for all other researchers’ relevant financial disclosures.
May 29, 2020
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Pembrolizumab extends PFS in relapsed or refractory classical Hodgkin lymphoma

Perspective from Lee Greenberger, PhD
Perspective from Joshua Brody, MD, PhD
Source/Disclosures
Source:

Kuruvilla J, et al. Abstract 8005. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.


Disclosures: Merck Sharp & Dohme funded this study. Kuruvilla reports research funding from, honoraria from or consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Karyopharm Therapeutics, Merck, Novartis, Pfizer, Roche and Seattle Genetics. Please see the abstract for all other researchers’ relevant financial disclosures.
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Pembrolizumab extended PFS compared with brentuximab vedotin for patients with relapsed or refractory classic Hodgkin lymphoma, according to study results presented during the ASCO20 Virtual Scientific Program.

The results — from an interim analysis of the randomized phase 3 KEYNOTE-204 study — suggest pembrolizumab (Keytruda, Merck) monotherapy should be the standard of care for this population, researchers concluded.

“Both of these agents clearly have a role in this disease,” John Kuruvilla, MD, hematologist and associate professor of medicine at Princess Margaret Cancer Centre and University of Toronto, told Healio. “Brentuximab vedotin initially established itself in this setting, and this randomized study shows pembrolizumab is superior, but I don’t look at it as if brentuximab vedotin has gone away. We just have another generation of active treatments. We already have refined where we can use brentuximab vedotin by moving it earlier, and I think this will show the same strategy needs to be taken with checkpoint inhibitors.”

John Kuruvilla, MD
John Kuruvilla

An estimated 15% to 20% of patients with classical Hodgkin lymphoma — the most common type of Hodgkin lymphoma — do not achieve remission after first-line treatment, Kuruvilla said. Prognosis is poor for these patients, many of whom are young, so additional effective therapies are needed.

Pembrolizumab extended PFS compared with brentuximab vedotin for patients with relapsed or refractory classic Hodgkin lymphoma.

Pembrolizumab — an anti-PD-1 therapy — is approved in the United States for treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma who relapsed after three or more prior lines of therapy.

The international, open-label KEYNOTE-204 study compared pembrolizumab with brentuximab vedotin (Adcetris, Seattle Genetics), an antibody-drug conjugate directed at CD30, among 304 adults with relapsed or refractory classical Hodgkin lymphoma who either underwent or were ineligible for autologous stem cell transplant.

All patients had measurable disease and an ECOG performance status of 0 or 1, and 15 patients had received prior brentuximab vedotin.

Researchers assigned patients pembrolizumab dosed at 200 mg or brentuximab vedotin dosed at 1.8 mg/kg (maximum 180 mg per dose) on day 1 of each 3-week cycle. Treatment continued for up to 35 cycles.

Researchers stratified randomization by prior stem cell transplant and status after first-line therapy (primary refractory vs. relapsed within less than 12 months after completion vs. relapsed 12 months or longer after completion).

PFS by blinded independent central review per International Working Group criteria — including clinical and imaging data after autologous stem cell transplant or allogeneic stem cell transplant — and OS served as co-primary endpoints. Other endpoints included PFS secondary, which excluded clinical and imaging data after autologous or allogeneic stem cell transplant; objective response rate assessed by blinded independent central review; PFS by investigator review and safety. Duration of response assessed by blinded independent central review served as an exploratory endpoint.

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Kuruvilla and colleagues presented data of 300 patients (pembrolizumab, n = 148; brentuximab vedotin, n = 152).

Median follow-up was 24.7 months (range, 0.6-42.3). Median time on treatment was 305 days (range, 1-814) in the pembrolizumab group and 146.5 days (range, 1-794) in the brentuximab vedotin group. At the time of data cutoff, 256 patients had discontinued treatment.

The primary PFS analysis showed a statistically significant PFS benefit with pembrolizumab (median, 13.2 months vs. 8.3 months; HR = 0.65; 95% CI, 0.48-0.88). A higher percentage of pembrolizumab-treated patients remained progression free at 12 months (53.9% vs. 35.6%).

Researchers observed the benefit with pembrolizumab in all evaluated subgroups, including patients who had not undergone autologous stem cell transplant (HR = 0.61), those with primary refractory disease (HR = 0.52), and patients who either received prior brentuximab vedotin (HR = 0.34) or were naive to the agent (HR = 0.67).

Researchers also reported improvement in other endpoints with pembrolizumab, including PFS secondary (median, 12.6 months vs. 8.2 months; HR = 0.62; 95% CI, 0.46-0.85), investigator-assessed PFS (median, 19.2 months vs. 8.2 months; HR = 0.49; 95% CI, 0.36-0.67), ORR (65.6% vs. 54.2%), complete response rate (24.5% vs. 24.2%) and median duration of response (20.7 months vs. 13.8 months).

Both drugs exhibited safety profiles consistent with prior reports.

A lower percentage of patients assigned pembrolizumab than brentuximab vedotin experienced grade 3 to grade 5 treatment-related adverse events (19.5% vs. 25%). One patient assigned pembrolizumab died due to treatment-related pneumonia.

Slightly more than 10% of pembrolizumab-treated patients developed pneumonitis. These patients were treated successfully with corticosteroids, and no deaths occurred due to these toxicities.

Peripheral neuropathy in the brentuximab vedotin group appeared manageable, Kuruvilla said.

Per study protocol, OS was not formally tested during the interim analysis. The study will continue so researchers can evaluate OS, and additional data could be available in the next 12 to 18 months, Kuruvilla said.

“You’re always concerned in Hodgkin lymphoma that the bar is set high. There are so many effective therapies and people can go on to other treatments and OS advantages are frequently elusive,” he told Healio. “That being said, given the large effect we saw with the drug in terms of the HR for PFS, we might actually see a survival advantage. I think that would be quite a surprise, but it would validate the benefit of checkpoint inhibitors in this disease.” – by Mark Leiser

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Reference:

Kuruvilla J, et al. Abstract 8005. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.

Disclosures: Merck Sharp & Dohme funded this study. Kuruvilla reports research funding from, honoraria from or consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Karyopharm Therapeutics, Merck, Novartis, Pfizer, Roche and Seattle Genetics. Please see the abstract for all other researchers’ relevant financial disclosures.