This past weekend in the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, John Kuruvilla, MD, presented results of the phase 3 KEYNOTE-204 trial, reporting that pembrolizumab significantly increased progression-free survival compared with brentuximab vedotin in patients with relapsed/refractory classic Hodgkin lymphoma. In this interview with i3 Health, Dr. Kuruvilla, an Associate Professor of Medicine at the University of Toronto, discusses the challenges of treating patients with relapsed/refractory classic Hodgkin lymphoma and the benefits of pembrolizumab for patients with this disease.
What are some of the most challenging aspects of treating patients with relapsed/refractory classic Hodgkin lymphoma?
John Kuruvilla, MD: Relapsed/refractory classic Hodgkin lymphoma is a challenging area, particularly given the heterogeneity of the patient population. For a large number of patients, treatment is given in the second-line setting with curative intent, and a good proportion of patients will be cured by autologous stem cell transplantation (ASCT). Unfortunately, for patients who experience disease progression after transplant and for those who are ineligible for transplant due either to comorbidities or to a lack of disease response, there is no proven curative treatment. Therefore, goals in the palliative setting are to provide disease control with good quality of life.
Historically, this area was a challenge, given the lack of novel agents. However, we have recently seen developments, including antibody-drug conjugates such as the anti-CD30 antibody brentuximab vedotin and, more recently, checkpoint inhibitors such as the anti–programmed death-1 (anti–PD-1) antibodies pembrolizumab and nivolumab, which are now approved for these patients. Choosing between agents can be difficult due to the different toxicity profiles and, until recently, a lack of randomized data.
Can you comment on the significance of your findings?
Dr. Kuruvilla: KEYNOTE-204 was a large randomized clinical trial comparing pembrolizumab with brentuximab vedotin in patients with relapsed/refractory classic Hodgkin lymphoma who had received at least one prior line of therapy and who had disease progression after ASCT or were ineligible for ASCT. The trial was the first to randomize patients in this setting. It demonstrated a statistically significant and clinically meaningful benefit in progression-free survival for pembrolizumab compared with brentuximab vedotin, approximately 13 versus 8 months. The toxicity profiles of both agents were generally safe and kept in line with the significant experience with both agents in clinical practice.
How do you foresee the treatment of relapsed/refractory classic Hodgkin lymphoma evolving in the coming years?
Dr. Kuruvilla: KEYNOTE-204 demonstrates a clear role for pembrolizumab as the preferred treatment in this setting. Additional studies are looking at combination approaches, such as brentuximab and nivolumab in CheckMate-812. New treatments such as CD30-directed chimeric antigen receptor (CAR) T-cell therapies are also being studied. Challenging patient populations will continue to include elderly patients, who are underrepresented in many clinical trials, as well as patients who fail all of these novel approaches.
What questions do you commonly encounter from patients with relapsed/refractory classic Hodgkin lymphoma, and how do you counsel them?
Dr. Kuruvilla: There are generally two broad, common questions. The first refers to choices around salvage therapy approaches and ASCT in patients who are eligible for curative therapy. There are very few comparative trials in this setting, but ASCT is well established as the standard of care, and brentuximab vedotin remains an important consideration as consolidation post-ASCT in higher-risk patients. The second common question deals with how to best approach treatment for patients in the noncurative setting. KEYNOTE-204 provides a clear answer that pembrolizumab is the preferred therapy in this patient population. However, more studies are still needed.
About Dr. Kuruvilla
John Kuruvilla, MD, is an Associate Professor of Medicine at the University of Toronto and a hematologist in the Division of Medical Oncology and Hematology at The Princess Margaret Cancer Centre in Ontario, Canada. He specializes in the treatment of lymphoma, with a focus on salvage therapies. Dr. Kuruvilla has authored or coauthored numerous publications investigating novel therapeutics for patients with hematologic malignancies, including patients undergoing stem cell transplantation.
For More Information
Kuruvilla J, Ramchandren R, Santoro A, et al (2020). KEYNOTE-204: randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). J Clin Oncol (ASCO Virtual Scientific Program), 38(suppl_15). Abstract 8005. DOI:10.1200/JCO.2020.38.15_suppl.8005\
Clinicaltrials.gov (2020). A study of nivolumab plus brentuximab vedotin versus brentuximab vedotin alone in patients with advanced stage classical Hodgkin lymphoma, who are relapsed/refractory or who are not eligible for autologous stem cell transplant (CheckMate 812). NLM identifier: NCT03138499.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.