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Combination Therapy Effective for Untreated Hodgkin Lymphoma in Older Patients

May 17, 2024

June 2024

Lara C. Pullen, PhD

Lara C. Pullen, PhD, is a freelance medical writer in Chicago, Illinois.

Patients with classical Hodgkin lymphoma (cHL) who are older than 60 years have a poor prognosis with the current treatment regimens and experience more severe adverse events (AEs) than younger patients. The ECHELON-1 trial, for example, found that 37% of older patients treated with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine and 17% of older patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen experienced febrile neutropenia. Moreover, multiple studies have found that patients 60 years or older who were treated with ABVD were at increased risk of death from bleomycin lung toxicity.

Now, research indicates that a new combination chemotherapy comprised of prednisone, vinblastine, doxorubicin, and bendamustine (PVAB) is an effective firstline therapy for older patients with HL. Hervé Ghesquières, MD, PhD, of Hôpital Lyon Sud in France, and colleagues reported that the four-year cumulative risk of events in this patient population was 35% for progression and relapse, 9% for death from lymphoma, and 6% for non-lymphoma events. They published the results of the prospective phase II trial in Blood.

The trial involved 78 patients who were at least 61 years old with newly diagnosed, advanced-stage HL. Patients had an Eastern Cooperative Oncology Group performance status from 0 to 2 and adequate cardiac and renal function. Individuals 70 years or older received a mandatory geriatric assessment with the Mini Nutritional Assessment (MNA) and were only enrolled if their MNA score was at least 17, a status the authors labeled as “fit.” The authors did not describe the limitations of their study.

The researchers found that PVAB treatment yielded a complete metabolic response (CMR) rate of 77.5%, which they confirmed by blind central review (78.5%). At four years, the progression-free survival (PFS) was 50%. The in-study death rate from toxicity was less than 5%, and the researchers observed toxicity primarily in patients who were 70 years or older. About one-third (37%) of this older population experienced related serious AEs compared with 9.3% of younger patients.

After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%). Of those who died, 11 died from HL, four died from toxicity during treatment, six died from secondary cancers, and three died from other causes. Dr. Ghesquières said the data reinforce that the results of studies of older adults should be interpreted with the understanding that, in this age category, PFS is influenced by acute and chronic toxicities as well as death from other cancers.

When the team performed a prognostic analysis, they found that liver involvement (p=0.001), C-reactive protein level (p=0.0005), and lymphopenia (p=0.001) were all independently associated with PFS. The new findings confirm data from previous studies that showed the prognostic impact of comorbidities and functional status of older patients on PFS. Dr. Ghesquières said the study also reinforces the importance of functional geriatric assessments for this age category of patients with cHL.

“Ours was the first prospective trial for older patients with cHL and ‘fit’ condition in the Lymphoma Study Association,” Dr. Ghesquières said. “We showed a good inclusion rate and the feasibility of geriatric assessments.

“In the absence of new immunotherapies, the PVAB regimen could be viewed as a valuable non-bleomycin regimen for older patients with cHL and ‘fit’ conditions (good performance status, adequate cardiopulmonary function, and favorable functional condition as determined by a geriatric evaluation scale such as MNA),” he added.

Dr. Ghesquières noted, however, that the CMR rate of 77.5% means new firstline therapies such as PD-1 blockers are still needed for this population. “Of note,” he said, “at the time of initiation of PVAB protocol, there was no access to immunotherapies (brentuximab vedotin or PD1-inhibitors) in firstline therapy in daily practice.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Ghesquières H, Krzisch D, Nicolas-Virelizier E, et al. The phase 2 LYSA study of prednisone, vinblastine, doxorubicin, and bendamustine for untreated Hodgkin lymphoma in older patients. Blood. 2024. 143(11):983-995.

 

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