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1668 Brentuximab Vedotin-Based Regimens for Older Patients with Newly Diagnosed Classical Hodgkin Lymphoma – International, Multi-Center Real-World Experience

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Hodgkin lymphoma, Lymphomas, Elderly, Clinical Research, Diseases, Real-world evidence, Adverse Events, Lymphoid Malignancies, Human, Study Population
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Efrat Luttwak, MD1, Swetha Kambhampati, MD2, Esther Drill, DrPH3*, Nivetha Ganesan, MPH3*, Liron Hofstetter4*, Ronit Gurion5*, Shlomzion Aumann, MD6,7*, Arnon Haran8,9*, Mika Geva10, Marc Panossian11,12*, Robert Stuver, MD1, Paul A. Hamlin, MD1, Ariela Noy, MD13, Alex F. Herrera, MD14 and Alison Moskowitz, MD1

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2City of Hope National Medical Center, Yorba Linda, CA
3Memorial Sloan Kettering Cancer Center, New York, NY
4Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel
5Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel
6Department of Hematology, Hadassah Medical Center, Jerusalem, Israel
7Hebrew University, Jerusalem, Israel
8Department of Hematology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
9Department of Hematology, Hadassah Medical Center, Mevaseret Zion, Israel
10Sheba medical center, Ramat Gan, Israel
11City of Hope, Durate, CA
12UCLA, Westwood, CA
13Memorial Sloan-Kettering Cancer Ctr., New York, NY
14City of Hope, Duarte, CA

Introduction: Despite excellent outcomes for young patients(pts) with HL, pts age 60 have less favorable outcomes with a 5-year PFS of about 60% (Cheng et al. Blood Advances 2022). This disparity is attributed to disease biology factors such as mixed cellularity, EBV positivity, and advanced-stage disease, as well as comorbidities that make patients more vulnerable to treatment toxicity, dose reductions, and interruptions. Brentuximab vedotin (BV) is increasingly used in the front-line setting for older pts. While BV concurrent with AVD (CON) is approved based on ECHELON-1, its use in older pts is limited by toxicity. A phase 2 study (Evens et al., JCO 2018) showed promising results by administering BV sequentially with AVD (SEQ) to improve safety. This study aimed to assess real-world outcomes with BV-based regimens in newly diagnosed older pts with HL.

Methods: This retrospective multicenter study was conducted at five medical centers in the US and Israel. Older pts age ≥60 consecutively diagnosed with HL between 03/2013-04/2023 were identified. Data on demographics, comorbidities (including cumulative illness rating scale-geriatrics [CIRS-G] score), AEs, treatment reductions, interruptions, PFS and OS were manually collected from electronic medical records.

Results: 136 pts were treated with BV-based regimens. Pt characteristics included a median age of 71 years (range 60-91), 65% male, a median CIRS-G score of 5 (range 0-16), 34% with a history of other malignancy, 54% stage IV disease, 29% with bone marrow involvement, 67% with B symptoms, 46% EBV positive in tumor, and 32% with non-nodular sclerosis histology.

Of these pts, 56 (41%) received CON BV-AVD, 54 (40%) were treated with SEQ BV-AVD; the rest (26, 19%) received BV monotherapy or BV-based palliative regimens.

Patients treated with CON BV-AVD were younger compared to those treated with SEQ BV-AVD (median 69 vs. 72 years old, p=0.049); Other baseline characteristics did not differ significantly between the two groups.

At a median follow up of 2.3 years (range 0.06-10.4), 2-year PFS and OS were 65% (95% CI 56-74%) and 83% (95% CI 76-90%), respectively. After excluding 26 pts treated with palliative regimens, 2-year PFS and OS were 73% (95% CI 64-83%) and 86% (95% CI 80-94%), respectively. We found no significant difference in PFS between SEQ and CON BV-AVD (76% vs. 70% 2-year PFS; p=0.5). In a multivariable Cox regression analysis including age and treatment regimen (SEQ or CON), the regimen was not statistically significant (p=0.2) with no difference in OS (p=0.7).

The most common AEs were neuropathy (all 44%/CON 45%/ SEQ 48%), infections (all 29%/CON 29%/ SEQ 26%), and neutropenic fever (all 16%/CON 28%/SEQ 11%), leading to treatment interruption in 33% of pts and treatment reduction in 52%, primarily involving BV. Of 107 patients treated with curative intent with full treatment data, 78 (73%) completed six cycles of AVD. However, only 58 (54%) completed the treatment as initially planned, mainly due to toxicity. Patients on CON BV-AVD were significantly more likely to complete treatment as planned when com­pared to those on SEQ (74% vs 34%, p<0.001).­ Rate of treatment interruption between cycles, or dose reduction did not differ significantly between CON and SEQ regimens.

During the study follow-up, 20 patients treated with curative intent died: 5 from infections (2 CON/3 SEQ including 3 from COVID-19), 7 from disease progression (4 CON/3 SEQ), and 8 from other comorbidities (2 CON/ 6 SEQ).

Among 36 pts who relapsed or had primary refractory disease, 4 died upon progression, and 2 were missing information after progression. Thirteen underwent treatment with PD-1-based combinations, while 17 received alternative chemotherapies.

Conclusions: In a multicenter study, evaluating the real-world outcomes of frontline BV in elderly HL pts, both CON and SEQ BV-AVD regimens demonstrated comparable efficacy and safety to those reported previously and to each other. More SEQ pts discontinued the treatment plan. SEQ BV-AVD had similar outcomes to CON BV-AVD, even after adjusting for age, indicating SEQ may not mitigate the adverse outcomes associated with older age. Recently, SWOG 1826 reported nivolumab-AVD over BV-AVD in advanced stage HL (Herrera et al., ASCO and ICML 2023) with similar findings in geriatric subsets (Torka et al, ICML 2023; Rutherford et al, ASH 2023). These finding support combining anti-PD-1 in frontline treatment for older patients.

Disclosures: Kambhampati: Genentech: Research Funding; Genmab: Consultancy, Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; ADC-Therapeutics: Research Funding. Gurion: Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Medison: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Stuver: Pfizer: Research Funding. Noy: Cornerstone Pharma: Honoraria, Research Funding; PER: Honoraria; NSCI: Honoraria; OncLIve: Honoraria; janssen Global: Consultancy, Other: drug provided for research; Medallion Healthcare: Honoraria; health advance: Consultancy; EUSA: Consultancy; guidepoint global: Consultancy; clearview: Consultancy; epizyme: Consultancy; AstraZeneca: Consultancy; ADC therapeutics: Consultancy; Beigene: Consultancy. Herrera: ADC Therapeutics: Consultancy, Research Funding; Karyopharm: Consultancy; Adicet Bio: Consultancy; Caribou Biosciences: Consultancy; Regeneron: Consultancy; Tubulis: Consultancy; Gilead Sciences: Research Funding; KiTE Pharma: Research Funding; Allogene Therapeutics: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Genmab: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Moskowitz: ADC therapeutics: Research Funding; Beigene: Research Funding; Brystal-Meyers Squibb: Research Funding; Incyte: Research Funding; Merck: Research Funding; Miragen Therapeutics: Honoraria; Seattle Genetics: Honoraria, Research Funding; Secura Bio: Research Funding; Takeda Therapeutics: Honoraria; Tessa Therapeutics: Honoraria.

*signifies non-member of ASH