Among older adult patients with classical Hodgkin lymphoma (cHL), frontline treatment with the combination of the immunotherapy Opdivo (nivolumab) plus the chemotherapy drugs doxorubicin, vinblastine and dacarbazine (N-AVD) was found to be highly effective and well-tolerated despite the presence of a wide range of geriatric impairments, researchers have reported.
Researchers, presenting their findings in the Journal of Clinical Oncology, stated that the combination “produces excellent outcomes for untreated older patients with cHL. It is well tolerated with low rates of [immune-related side effects] and treatment discontinuations. [Older adults] with cHL across a wide range of geriatric impairments benefit from N-AVD and should be considered for curative chemoimmunotherapy as long as they are eligible to receive anthracyclines.”
In the phase 1/2 study, patients aged 60 years old or older with newly diagnosed cHL of any stage were treated with six cycles of AVD at standard doxes, plus 240 milligrams of Opdivo intravenously once every two weeks, on days 1 and 15, of each cycle.
At a median follow-up of 49 months among 37 response-evaluable patients, the three-year progression-free survival and overall survival rates were 79% and 97%, respectively. For patients with stage 3 or 4 disease, the three-year progression-free survival rates were 80% and 97%.
Glossary:
Adrenal insufficiency: when the adrenal glands don’t make enough of the hormone cortisol, according to Johns Hopkins Medicine.
Anthracyclines: according to the National Cancer Institute, a type of antibiotic used to treat cancer that damages the DNA in cancer cells.
Colitis: inflammation of the colon.
Febrile neutropenia: when patients with neutropenia, or low count of a type of white blood cell called neutrophils, experience a fever.
International Prognostic Score: a risk stratification tool for some patients with cancer
Interstitial nephritis: inflammation of the tubules of the kidneys and the tissue surrounding them.
Peripheral motor neuropathy: damage to the nerves that control muscles and movement in the body, such as moving your hands and arms or talking, according to Johns Hopkins Medicine.
Pneumonitis: inflammation of the lung tissue.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time a patient lives, regardless of disease status.
Half of patients experienced grade 3 (severe) or 4 (life-threatening) treatment-related side effects, with four, or 10% of patients, stopping treatment due to treatment-related side effects.
Participating patients had a median age of 66 years, and 38% of them were 70 or older, 78% had stage 3 or 4 disease, 68% had an International Prognostic Score of 3 or greater, 82% were dependent in at least activity of daily living, 23% were dependent in at least one instrumental activity of daily living, 50% with had impaired timed up and go tests and 40% with polypharmacy, meaning they were on more than 10 medications a day, researchers reported.
Eight percent of patients experienced febrile neutropenia. With the exception of one patient who experienced grade 4 adrenal insufficiency, endocrine immune-related side effects were all grade 1 (mild) or 2 (moderate). Researchers reported that nonendocrine immune-related side effects included colitis (one case of grade 2 and one case of grade 3), grade 3 interstitial nephritis (one patient), grade 3 hepatitis (one patient), grade 2 pneumonitis (one patient), grade 2 peripheral motor neuropathy (one patient) and grade 1 or 2 rash (nine patients). While seven patients required systemic steroids for the treatment of immune-related side effects, no unexpected toxicities were noted.
Six patients experienced cHL relapse, and no deaths were attributable to cHL. The one death on the study, researchers noted, was attributed to COVID-19 pneumonia.
Researchers reported that there was no correlation between baseline geriatric impairments and survival outcomes or toxicities.
If confirmed by longer follow-up in the S1826 trial, “the safety and high activity of N-AVD will lead to a new standard of care for most older patients with Hodgkin lymphoma,” Journal of Clinical Oncology editor-in-chief Dr. Jonathan W. Friedberg noted when discussing the relevancy of the study in a contextual piece published alongside the findings.
Reference:
“Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine, Dacarbazine as Frontline Therapy in Older Adults With Hodgkin Lymphoma” by Dr. Pallawi Torka, et al., Journal of Clinical Oncology.
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