Brentuximab vedotin (BV) + AVD for newly diagnosed classic Hodgkin lymphoma (cHL): incidence and management of peripheral neuropathy (PN) in a multi‐institution cohort

Introduction: BV in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is the new standard of care for newly diagnosed stage III/IV cHL. In the pivotal ECHELON-1 trial, PN was the most common toxicity, seen in 67% of patients (pts) and leading to discontinuation of BV in 6.6%. However, PN from BV+AVD in cHL has not been studied in a non-trial setting, where clinicians may have different strategies for managing it. Methods: We conducted a multi-site, retrospective study to characterize PN in pts who were planned to receive 6 cycles of BV+AVD for newly diagnosed cHL before 9/2022. Data was obtained from medical records and PN was graded retrospectively using CTCAE v5.0 criteria. Multivariable logistic regression was used to assess factors associated with PN. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan Meier method. A Cox proportional hazards model was used to test the effect of discontinuation on PFS. Results: 153 pts from 10 US institutions were eligible. Median age was 35 years (range 18–76) with 22% of pts over 60 years old. Thirty-four pts (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage (8% stage I/II), performance status (3% ECOG 3+), preexisting PN (6%), or other comorbidities including HIV and other malignancies (10%). Of advanced stage pts, 41% had IPS 4–7. Median no. BV+AVD cycles was 6 (range 1–6). PN was reported by 80% of pts during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of pts due to PN leading to BV discontinuation in 23% with median no. of doses omitted of 4 (range 1–10), dose reduction in 17% and temporary dose hold in 4%. Vinblastine was modified in 17% of pts due to PN including discontinuation or temporary hold in 10% and dose-reduction in 7%; in 35% of pts with vinblastine modification, BV was continued. None of the factors assessed (age, sex, baseline PN, diabetes mellitus) predicted development of any grade PN. However, higher initial dose of BV in mg (based on weight) was associated with increased risk of grade 2+ PN (OR 1.03, 95% CI: 1.01–1.05, p = 0.002). With median follow up of 24 months (range 0.33–87), PN resolution was documented in 36% and improvement in 33% at last follow up. Ongoing G2+ PN was present in 13% of pts at last follow up. 2-year PFS for the advanced stage patients (n = 140) was 82.7% (95% CI: 0.76–0.90) and OS was 97.4% (95% CI: 0.944–1). Discontinuation of BV due to neuropathy did not affect PFS (HR 1.1, 95% CI: 0.45–2.5). Encore Abstract - previously submitted to ASCO 2023 Keyword: Hodgkin lymphoma Conflicts of interests pertinent to the abstract. S. M. Bair Consultant or advisory role: TG Therapeutics, Abbvie, Arcellx N. Epperla Consultant or advisory role: Karyopharm, TG Therapeutics, Beigene, Novartis Honoraria: Genzyme Research funding: AstraZeneca, Secura Bio S. Gaballa Consultant or advisory role: ADC Therapeutics, Epizyme, BeiGene, Kite M. Spinner Consultant or advisory role: Kite M. Messmer Stock ownership: Schrodinger C. B. Wagner Consultant or advisory role: Pfizer B. Hu Employment or leadership position: BMS, Novartis, GenMab, TG Therapeutics, Lilly Honoraria: MJH Life Sciences, BeiGene, Artiva, DAVA Oncology Research funding: Genentech, Crispr Therapeutics, MorphoSys, Caribou Biosciences, Repare Therapeutics Educational grants: MJH Life Sciences S. F. Huntington Consultant or advisory role: SeaGen, Janssen, Bayer, Genentech, Abbvie, Flatiron, Novartis, BeiGene, AstraZeneca, ADC Therapeutics, Epizyme, Merck, TG Therapetucis, Tyme, Arvinas Honoraria: SeaGen, Pharmacyclics, AstraZeneca Research funding: Celgene, DTRM, TG Therapeutics, Debiopharm Group, Agios Educational grants: Celgene, Bayer, Pharmacyclics, Genentech N. N. Shah Consultant or advisory role: Kite, Loxo/Lilly, TG Therapeutics, Incyte, Novartis, Juno, Janssen Stock ownership: Tundra Targeted Therapeutics Research funding: Miltenyi Biotec, Loxo/Lilly, Adaptive Biotechnologies Educational grants: Miltenyi Biotec M. E. Hughes Consultant or advisory role: AstraZeneca, Genzyme, Janssen, Abbvie, Karyopharm Research funding: Acerta Pharma, HOPA E. A. Chong Consultant or advisory role: Novartis, Beigene, Kite, Tessa, Juno S. D. Nasta Research funding: Pharmacyclics, Roche, Rafael, FortySeven/Gilead S. K. Barta Consultant or advisory role: Affimed, Daiichi Sankyo, Kyowa Kirin Honoraria: Kyowa Kirin, Seagen, Acrotech D. J. Landsburg Consultant or advisory role: ADC Therapeutics, Calithera, Epizyme, Morphosys Research funding: Curis, Triphase J. Svoboda Consultant or advisory role: Seagen, BMS, Astrazeneca, Pharmacyclics, Adaptive Biotechnologies, Atara Research funding: Seagen, Celgene, Pharmacyclics, Merck, BMS, Incyte, AstraZeneca, Adaptive Biotechnologies