John Kuruvilla, MD, FRCPC, a clinician investigator in the Cancer Clinical Research Unit at Princess Margaret Cancer Centre, discusses the safety of pembrolizumab (Keytruda) versus brentuximab vedotin (Adcetris) in classical Hodgkin lymphoma (CHL).

, the phase 3 KEYNOTE-204 trial enrolled patients with CHL who relapsed following an autologous stem cell transplant or were ineligible for transplant. They were randomized to 35 cycles of either pembrolizumab or brentuximab vedotin. 

The toxicity is important to consider because both drugs have different safety profiles. It is known that when the antibody-drug conjugate brentuximab vedotin is combined with chemotherapy, that can contribute to peripheral neuropathy, says Kuruvilla; this was shown in the control arm. However, patients recovered from that event and were still able to do reasonably well, adds Kuruvilla.

In the experimental arm with pembrolizumab, it was known that there were going to be some potential toxicities, adds Kuruvilla. The common immune-related toxicities reported with the agent, which are generally mild and grade 1/2, were as expected. The more worrisome toxicity is pneumonitis, which has been described with this class of agent. In general, approximately 10%-11% of those who received pembrolizumab experienced this event. Half of these events were grades 1/2 and the other half were grade 3/4. Patients who experienced pneumonitis were successfully managed with the use of corticosteroids, although a few patients required discontinuation.

Overall, the effect was still broad no treatment-related deaths from toxicity were reported. Given what was known about this class of agent, toxicity effects the minority while the majority still benefits, concludes Kuruvilla.

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John Kuruvilla, MD, FRCPC, discusses the safety of pembrolizumab (Keytruda) versus brentuximab vedotin in classical Hodgkin lymphoma.

Dr. Kuruvilla on the Safety of Pembrolizumab in Classical Hodgkin Lymphoma

John Kuruvilla, MD, FRCPC, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses the broad utility of pembrolizumab (Keytruda) in Hodgkin lymphoma.

At the 2020 ASCO Virtual Scientific Program, findings from the phase 3 KEYNOTE-204 trial demonstrated a 35% reduction in the risk of disease progression or death with pembrolizumab compared with brentuximab vedotin (Adcetris) in patients with classical Hodgkin lymphoma who relapsed post-transplant or were ineligible for transplant.

Moreover, the progression-free survival benefit with pembrolizumab was observed across prespecified patient subgroups.

Biomarkers were not included in this study as there no well-defined predictive targets in Hodgkin lymphoma, explains Kuruvilla.

As such, pembrolizumab may broadly apply to patients in this population who fit the inclusion criteria and have relapsed following or who are ineligible for transplant, concludes Kuruvilla.

John Kuruvilla, MD, FRCPC, discusses the broad utility of pembrolizumab in Hodgkin lymphoma.



Dr. Kuruvilla on the Broad Utility of Pembrolizumab in Hodgkin Lymphoma

John Kuruvilla, MD, FRCPC, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses the treatment landscape in relapsed/refractory Hodgkin lymphoma. 

Over the past decade, the armamentarium of relapsed/refractory Hodgkin lymphoma has expanded, says Kuruvilla.

Early efficacy data with lenalidomide (Revlimid), mTOR inhibitors, and HDAC inhibitors like panobinostat were promising, explains Kuruvilla.

However, the approvals of the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) led to a drastic shift in the management of patients with Hodgkin lymphoma.

Additionally, the approval of the antibody-drug conjugate brentuximab vedotin (Adcetris) in combination with chemotherapy has had a significant impact on the treatment paradigm of patients with stage III or IV classical disease. 

Going forward, these active agents may be moved into the frontline setting to offer potentially curative options for patients with Hodgkin lymphoma, concludes Kuruvilla. 

John Kuruvilla, MD, FRCPC, discusses the treatment landscape in relapsed/refractory Hodgkin lymphoma. 


Dr. Kuruvilla on the Treatment Landscape in Relapsed/Refractory Hodgkin Lymphoma

John Kuruvilla, MD, FRCPC, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses findings from the phase 3 KEYNOTE-204 trial in Hodgkin lymphoma.

In the phase 3 trial, patients who had relapsed following autologous stem cell transplant (ASCT) or were ineligible for ASCT were randomized to pembrolizumab (Keytruda) or brentuximab vedotin (Adcetris). Progression-free survival (PFS) served as the primary end point of the trial.

At a median follow-up of 24.7 months, the median PFS was 13.2 months with pembrolizumab versus 8.3 months with brentuximab vedotin, translating to a 35% reduction in the risk of progression or death (HR, 0.65; 95% CI, 0.48-0.88; 

 =.00271). The benefit was observed in all subgroups, including patients with no ASCT (HR, 0.61), primary refractory disease (HR, 0.52), prior brentuximab vedotin exposure (HR, 0.34), and no prior exposure to brentuximab vedotin (HR, 0.67). Per investigator assessment, PFS was longer with pembrolizumab versus brentuximab vedotin, at 19.2 months versus 8.2 months, respectively (HR, 0.49; 95% CI, 0.36-0.67).

The adverse effect (AE) profiles of both drugs were consistent with past experiences, says Kuruvilla. Grade 3 to 5 treatment-related AEs occurred in 19.6% of patients in the pembrolizumab arm versus 25.0% of patients in the brentuximab arm.

John Kuruvilla, MD, FRCPC, discusses findings from the phase 3 KEYNOTE-204 trial in Hodgkin lymphoma.

John Kuruvilla, MD, FRCPC

Articles

Dr. Kuruvilla on the Safety of Pembrolizumab in Classical Hodgkin Lymphoma

Dr. Kuruvilla on the Broad Utility of Pembrolizumab in Hodgkin Lymphoma

Dr. Kuruvilla on the Treatment Landscape in Relapsed/Refractory Hodgkin Lymphoma

Dr. Kuruvilla on Findings From the KEYNOTE-204 Trial in Hodgkin Lymphoma