Real-world clinical outcomes with novel agent combination therapies for the frontline treatment of pediatric and adult advanced-stage Hodgkin lymphoma
Year: 2025
Type: conference-abstract
Abstract: Introduction: Brentuximab vedotin (BV) and nivolumab (N) have resulted in significant progress in the treatment of advanced-stage Hodgkin lymphoma (AS-HL). The SWOG 1826 trial demonstrated a progression-free survival (PFS) and safety benefit with frontline N-AVD (doxorubicin, vinblastine, and dacarbazine) compared to BV-AVD; however, real-world data are limited. This study evaluates the efficacy, toxicity and feasibility of these regimens outside of the clinical trial setting. Methods: This multicenter retrospective study evaluates pediatric (age 12-17) and adult patients (pts)(age ≥18 years(yrs)) treated with BV-AVD or N-AVD in the real-world setting for AS-HL. Fifteen institutions contributed data, and Lugano criteria were utilized to assess response. Adverse events (AEs) graded according to CTCAE 5.0 criteria. Survival outcomes evaluated relative to treatment start date. Results: Between 9/2011 - 2/2025, 556 pts received BV-AVD (433 pts - 78%) or N-AVD (123 pts – 22%). Median age 32 yrs (range, 12-90), 41.7% (n=232) of pts were female, 5.4% (n=26) ECOG ≥2, 6.8% (n=38) were pediatric, and 16.5% (n=92) were older adults (age >60 yrs). Baseline characteristics, including age, sex, ECOG, stage, comorbidities, laboratories and disease characteristics (B symptoms, bulky disease, extranodal disease, stage) were comparable between N-AVD and BV-AVD (all p>0.05). Evaluating treatment delivery, 8% (n=34) of BV-AVD pts and 6% (n=7) of N-AVD pts were unable to complete the intended 6 cycles of therapy (p=0.56). Growth factor support was administered in 92.1% (n=386) receiving BV-AVD compared to 49.6% (n=60; primary prophylaxis: 32 pts, asymptomatic neutropenia: 17, neutropenic fever/infection: 5, other/unknown: 6) receiving N-AVD (p<0.0001). N-AVD was associated with higher rates of neutropenia (any grade (gr): 77.9% vs 48.9%, p<0.0001; gr ≥3: 57.4% vs 37.8%, p=0.0002) and any gr infections (34.2% vs 19.8%, p=0.001) compared to BV-AVD; however, gr≥3 infections (11.7% vs 8.6%, p=0.29) or febrile neutropenia (14.9% vs 13.8%, p=0.77) did not differ between N-AVD to BV-AVD. Dose delays were not significantly different (BV-AVD: 27.6% vs N-AVD: 26.4%, p=0.91), but dose reductions/omissions were more common in BV-AVD group (37.8% vs 13.3%, p<0.0001) compared to N-AVD. In pts treated with N-AVD, immune-related AEs of any gr occurred in 24.2% (n=29), with gr≥3 events in 8.3% (n=10). With BV-AVD, a higher incidence of cardiovascular toxicities (thrombosis, cardiac structural or arrythmia events - any gr: 13.6% vs 2.9%, p=0.01; gr≥3: 9.1% vs 0%, p=0.005) and neuropathy (any gr: 58.9% vs 21.5%, p<0.0001; gr≥3 11.6% vs 0%, p<0.0001) were found compared to N-AVD. Response rates were similar between BV-AVD and N-AVD: overall response rate 92% vs 97% (p=0.20), complete response rate 86% vs 90% (p=0.35). Progressive disease at end-of-therapy: 7.0% (BV-AVD) vs 2.6% (N-AVD). One-yr PFS in pts treated with N-AVD and BV-AVD was 91% (95% CI, 84-98%) and 88% (95% CI, 85-91%), respectively. No death events were observed in N-AVD group (1-yr OS: 100%), 24 deaths in BV-AVD group [1-yr OS: 98% (95% CI, 96-99)] secondary to: infection/sepsis - 10 pts, secondary malignancy - 3, HL - 2, cardiogenic shock - 1, unknown - 8. At current data cutoff, follow-up for N-AVD pts was short (median: 9.8 months vs 30.0 months) compared to BV-AVD, limiting direct survival comparisons. To balance follow-up, additional analyses were conducted on pts treated between 2022-2025 (n=339). No differences in PFS/OS were observed in pediatric pts or older adults (p>0.05); however, improved PFS was seen with N-AVD (1-yr PFS: 96 vs 87% p=0.04) compared to BV-AVD in adult patients (n=253; 18-60 yrs). Conclusions: This large real-world multicenter study demonstrates that response rates and 1-yr survival outcomes with N-AVD and BV-AVD are similar to the published SWOG 1826 trial (N-AVD vs BV-AVD: 1-yr PFS: 94% vs 86%, Herrera et al. 2024). Increased cardiovascular AEs, dose reductions/omissions and neuropathy with BV-AVD indicate better tolerability with N-AVD; however, the higher rate of febrile neutropenia and infections in comparison to SWOG 1826 in N-AVD pts suggests that growth factor prophylaxis may be beneficial in select high-risk subgroups. Longer-term follow-up data will be available at time of presentation, but even with short follow-up, pts (age 18-60) demonstrated a significant PFS benefit with N-AVD, supporting the change to N-AVD as the standard for AS-HL.
Source: Blood
Authors: Karan Chohan, Lei Feng, Hunter Cochran, Maya Rosenberg, Leidy Isenalumhe, Elif Yilmaz, Seo-Hyun Kim, Yun Kyoung Tiger, Pallawi Torka, Hayley Flanagan, Sharon Castellino, Jonathan Bender, Radhamani Kannaiyan, Justin Kahla, B. Paige DePriest, Hiba Narvel, Samanta Catueno, Katherine Tobon, Julia Fadul, Patricia Faulkenberry, Amy Ayers, Sunita Nathan, Salmaan Mubeen, Efrat Luttwak, Jamie Flerlage, Robin Norris, Supreet Kaur, Olivia Tran, Chalothorn Wannaphut, Ashleigh Hawk, Miriam Garcia, Branko Cuglievan, Peter Riedell, Kris Mahadeo, Mehdi Hamadani, Catherine Diefenbach, Nancy Bartlett, Sairah Ahmed
Institutions: The University of Texas MD Anderson Cancer Center, Washington University in St. Louis, NYU Langone Health, New York University, Moffitt Cancer Center, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Rush University Medical Center, Rutgers Cancer Institute, Memorial Sloan Kettering Cancer Center, University of Rochester Medicine, Children's Healthcare of Atlanta, Cincinnati Children's Hospital Medical Center, The University of Texas at San Antonio Health Science Center, University of Chicago, Duke University, Medical College of Wisconsin
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417008358
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