Older patients with classical Hodgkin lymphoma unsuitable for conventional chemotherapy had high rates of durable responses with two brentuximab vedotin (BV; Adcetris) regimens, one that omitted chemotherapy, a small prospective study showed.

Brentuximab plus the alkylating agent dacarbazine (DTIC) produced an objective response rate (ORR) of 95% in 22 patients, whereas brentuximab plus nivolumab (Opdivo) led to responses in 86% of 21 patients. Two-thirds of patients achieved complete responses with each regimen.

Patients treated with the dacarbazine regimen had a median progression-free survival (PFS) of almost 4 years and the median had yet to be reached with the nivolumab regimen after 51.6 months of follow-up, reported Jonathan Friedberg, MD, MMSc, of the University of Rochester Wilmot Cancer Institute in New York, and co-authors in Blood.

“Despite a high median age, inclusion of patients up to 88 years, and frailty demonstrated on comprehensive geriatric assessment, our results compare favorably with our previous single-agent and combination studies in older patients incorporating BV,” the authors wrote. “With a median follow-up of almost 4 years, the mDOR [median duration of response] and median PFS have not been reached, supporting the inference that some patients treated with this regimen may go on to be cured. Comprehensive geriatric assessments demonstrated similar rates of frailty and geriatric syndromes in the BV-nivolumab cohort compared with the BV-DTIC cohort.”

The high response rates and durability of responses do raise the question of whether some patients with classical Hodgkin lymphoma, irrespective of age, might be cured without standard combination chemotherapy, agreed the author of an accompanying commentary.

“Traditionally, the dogma has been that a cure can only come from some combination of an anthracycline, a vinca alkaloid, and a drug that rhymes with -carbazine,” wrote Ryan C. Lynch, MD, of the University of Washington and Fred Hutchinson Cancer Center in Seattle. “Personal anecdotes as well as emerging data from studies like this suggest there may be another way.”

“Using noninvasive genotyping and circulating tumor DNA may help identify patients who are either at lower risk at baseline or perhaps cured far earlier during their treatment than anticipated,” Lynch continued. “Given newer drugs and emerging technologies, we should resolve to design the next generation of studies with the goals of less or, dare I say, no chemotherapy at all, allowing us to reserve more toxic chemotherapy regimens for only those who truly need it.”

Overall survival for adults with advanced classical Hodgkin lymphoma has improved dramatically over the past 2 decades, Friedberg and co-authors noted in their introduction. Nonetheless, older patients have inferior outcomes. A recent analysis of Medicare patients showed that only a fourth received full-course chemotherapy, half received partial regimens or single-agent treatment, and the remaining fourth received no treatment at all.

Full-course therapy improves survival, but the observation is confounded by selection bias as frail patients and those with significant comorbidities are less likely to be treated with the regimens, the authors pointed out.

A recent study of brentuximab monotherapy in combination with dacarbazine led to objective responses exceeding 90%, which proved to be durable. The combination of brentuximab and nivolumab has led to high rates of durable complete responses in younger patients. The cumulative results provided a rationale to evaluate brentuximab in combination with dacarbazine or nivolumab in older patients with previously untreated classical Hodgkin lymphoma.

In the non-comparative phase II study, the researchers enrolled patients ages 60 and older with untreated classical Hodgkin lymphoma who were considered unfit for conventional chemotherapy. Eligible patients had three or more general comorbidities or at least one significant comorbidity.

The 22 patients in the dacarbazine cohort had a median age of 69, 73% were men, 73% had stage III/IV disease, and three-fourths reported limitations in physical functioning.

The ORR of 95% included complete responses in 64% of patients. After a median follow-up of 63.6 months, median duration of response was 46 months, and median PFS was 47.2 months. Median duration of complete response and median overall survival had yet to be reached.

The most common treatment-emergent adverse events (TEAEs) were peripheral neuropathy (77%), constipation (45%), fatigue (45%), and nausea (41%). The most common grade ≥3 TEAEs were peripheral neuropathy (27%) and neutropenia (9%).

The 21 patients in the nivolumab cohort had a median age of 72, 71% were men, 77% had grade III/IV disease, and 43% reported limitations in physical functioning. The 86% ORR included complete responses in 67% of patients. After a median follow-up of 51.6 months, median duration of response, median duration of complete response, median PFS, and median overall survival had yet to be reached.

The most commonly reported TEAEs with brentuximab and nivolumab were fatigue (76%), peripheral neuropathy (48%), constipation (48%), nausea (48%), and diarrhea (48%). Grade ≥3 TEAEs included increased lipase (24%), motor peripheral neuropathy (19%), and sensory peripheral neuropathy (19%).

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