Adcetris-based combinations showed promise in treating older patients with classical Hodgkin lymphoma who are not eligible for traditional chemotherapy.
Recent research identified possible alternative treatments for older patients with classical Hodgkin lymphoma (cHL) who are ineligible for conventional chemotherapy.
Researchers, in findings published in the journal Blood, said their data “demonstrate safety and promising durable efficacy” of treatment with the antibody-drug conjugate (ADC) Adcetris (brentuximab vedotin) in combination with either the chemotherapy dacarbazine or the immune checkpoint inhibitor Opdivo (nivolumab).
“There are new, promising treatment options for older patients with Hodgkin lymphoma, particularly those who are not able to tolerate standard chemotherapeutic approaches,” said Dr. Jonathan W. Friedberg, director of the James P. Wilmot Cancer Institute and the Samuel Durand Professor of Medicine at the University of Rochester Medical Center, as well as the co-author of the study.
These findings bridge what had been a knowledge gap, as he explained.
“What we’ve learned over the last 10 years is that we don’t really know what the standard [of care] is [for older patients with cHL],” Friedberg said. “The median age of diagnosis is maybe around 29 years. Most of the clinical trials that enroll patients, although they may not have an upper age restriction, enrolled very few patients over the age of 60. Therefore, it was a real knowledge gap that even though 15% or so of Hodgkin lymphoma presents over the age of 70, we had very few patients who were treated in previous clinical trials for that age group.”
Trial Shows Promise for Adcetris Combo in cHL
In the study of patients who were at least 60 years old, 50% of those treated with dacarbazine had at least three general comorbidities or at least one significant comorbidity, versus 38% of those treated with Opdivo.
Learn more: Second Remission Likely After Retreatment With Keytruda for Patients with Hodgkin Lymphoma
Ninety-five percent (22 patients) of those treated with Adcetris and dacarbazine achieved objective response to treatment. Meanwhile 64% achieved complete response (the disappearance of the disease). Objective response and complete response rates were 86% and 67% among the 21 patients treated with Adcetris and Opdivo.
At a median follow-up of 63.6 months, the median duration of response (DOR) to Adcetris and dacarbazine was 46 months. The median progression-free survival (PFS; the time a patient lives following treatment without their disease spreading or worsening) was 47.2 months. Additionally, the median overall survival (OS; the time a patient lives following treatment, regardless of disease status) was not reached, meaning more than half of the patients in that cohort were still alive.
At a median follow-up of 51.6 months in the Adectris and Opdivo arm, DOR, PFS and OS had not yet been reached. As Friedberg explained, this means that more than half of the patients who responded to treatment had not yet experienced disease progression.
How Adcetris Works
Describing the science behind Adcetris, Friedberg said that “maybe a good analogy is it’s sort of like a smart bomb. The antibody helps to direct the treatment to the cancer cells, sparing normal cells, and then the conjugate is a poison that is attached to the antibody that then goes into the cancer cells and kills the cancer cells. For the most part, that’s how it’s felt that they are working in people. It’s not 100% perfect, there are side effects associated with these antibody-drug conjugates. And in the case of [Adcetris], the biggest side effect that we tend to see is neuropathy, which at times can be disabling and require the need for dose adjustment.”
Grade 3 or higher treatment-emergent side effects occurred in 10 patients (45%) in the Adectris and dacarbazine cohort and in 16 patients (76%) in the Adcetris and Opdivo cohort, researchers reported. Sensory peripheral neuropathy (PN, pain, numbness and tingling; 27%) and neutropenia (a low count of neutrophils, a type of white blood cell; 9%) were the most common in the dacarbazine arm and increased lipase (an enzyme that breaks down fat; 24%), motor PN (19%) and sensory PN (19%) were the most common in the Opdivo arm.
“Older patients should appreciate that in many lymphomas, chemotherapy is very appropriate and can be tolerated,” Friedberg said. “But [patients should also know] that there are options if either medical, comorbidity or other health concerns preclude the use of standard chemotherapy that are still quite effective and may even result in durable remissions.
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