N-AVD as a Frontline Therapy in Older Adults With CHL

Classical Hodgkin lymphoma (cHL) outcomes in older adults (OA) remain poor, even with curative therapy. The 5-year progression-free survival (PFS) for OA remains around 60% (Cheng, et al. Blood Advances 2022). The ECHELON-1 study demonstrated brentuximab-AVD association with higher incidences of toxicities in OA, without any significant benefit in PFS compared to ABVD. The CheckMate 205 study demonstrated the safety of nivolumab+doxorubicin, vinblastine, and dacarbazine (N-AVD). It included six patients (pts) over 60 and evaluated the safety and efficacy of N-AVD in older adults with classical Hodgkin lymphoma (cHL), a phase 2 trial. The study aimed to determine the impact of geriatric assessment (GA) at baseline on treatment toxicity in this population.

The study included pts aged 60 years and above with any cHL stage. The treatment involved intravenous administration of a combination of six cycles of AVD at standard doses along with nivolumab 240 mg on days 1 and 15 of each cycle. A GA was performed to measure function, comorbidity, cognition, psychological state, social activity/support, and nutritional status before the treatment. The study’s primary objective was to improve the 2-year PFS for OA with cHL from a historical control of 55% to 75% with N-AVD. The secondary objectives were 2-year overall survival (OS) and safety. The researchers utilized logistic regressions to analyze the mean scores of each domain of the GA for correlation with grade ³3 toxicities.

Of the 37 pts enrolled, 33 were evaluable for response, with 4 (too early). The median patient age was 66 (range 60-78), with approximately 41%pts ≥70 y. At diagnosis, 78% had stage 3 or 4 disease, 68% had an International Prognostic Score of 3 or higher, 54% had B symptoms, and 43% had extranodal disease. The overall response rate was 100% and 97%, and one patient showed a partial response due to a non-diagnostic biopsy. After a median follow-up of 37 months, 5 (14%) pts experienced HL relapse, and one pt died from HL. According to the study, the 2-year PFS and OS rates were 86.2% (95% CI: 74.4%–99.8%) and 96.4% (95% CI: 89.8%–100%), respectively. Of the pts, 41% experienced grade (gr) 3/4 treatment-related adverse events (TrAE). Only two pts (6%) taking nivolumab had to stop therapy due to TrAEs. Additionally, 5% of pts had treatment-related febrile neutropenia. The endocrine immune-mediated AEs (irAEs) were all Gr 1/2, while nonendocrine irAEs included Gr 3 hepatitis (n = 1), Gr 2 colitis (n = 1), Gr 2 pneumonitis (n = 1), and Gr 1/2 rash (n = 7). The meeting will share the analysis of GA data.

N-AVD proved effective and well-tolerated as frontline therapy for older adults with cHL. The phase 3 study comparing N-AVD with brentuximab-AVD will determine if N-AVD becomes standard care for pts with newly diagnosed cHL. Results will shape future treatment.

Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_107

Clinical Trials: https://classic.clinicaltrials.gov/ct2/show/NCT03907488
https://classic.clinicaltrials.gov/ct2/show/NCT02181738

Torka, P., Feldman, T., Savage, K., Ganesan, N., Hancock, H., Davey, T., Perez, L., Santarosa, A., Subzwari, S., Capadona, C., Yang, C., Galasso, N., David, K., Epstein-Peterson, Z., Khan, N., Kumar, A., Hamlin, P., Ghione, P., Lue, J., . . .  Moskowitz, A. PHASE 2 TRIAL OF NIVOLUMAB PLUS ADRIAMYCIN, VINBLASTINE, DACARBAZINE (N-AVD) AS FRONTLINE THERAPY IN OLDER ADULTS WITH HODGKIN LYMPHOMA. Hematological Oncology, 41, 161-162. https://doi.org/10.1002/hon.3163_107