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1672 Real World Experience with Sequential Brentuximab Vedotin Plus AVD Chemotherapy As Frontline Therapy for Older Patients with Classical Hodgkin Lymphoma: A Multicenter Retrospective Study

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Hodgkin lymphoma, Lymphomas, Diseases, Treatment Considerations, Lymphoid Malignancies, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Ariel Perez Perez, MD1, Nayef Abdel-Razeq, MD2*, Tiba Al Sagheer, PharmD1*, George Nahas, DO1, Jose Sandoval-Sus, MD3, Manny Alfonso, PharmD3*, Carlos Silva, MD3, Syeda Saba Kareem, PharmD4*, Katherine Tobon, PharmD, BS4*, Allison C. Rosenthal, DO5, Stephen M. Ansell, MD, PhD6, Yuliya PL Linhares, MD1, Muhamad Alhaj Moustafa, M.D., M.S.2 and Hayder Saeed, MD4

1Blood and Marrow Transplant Program, Miami Cancer Institute, Baptist Health South Florida, Miami, FL
2Division of Hematology, Mayo Clinic, Jacksonville, FL
3Moffitt Cancer Center at Memorial Healthcare System, Pembroke Pines, FL
4Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
5Division of Hematology/Oncology Mayo Clinic, Phoenix, AZ
6Division of Hematology, Mayo Clinic, Rochester, MN

Introduction:

The treatment of older patients with advanced stage classical Hodgkin lymphoma (cHL) is challenging and outcomes remain poor compared to younger patients (pts). A subgroup analysis of older pts (aged ≥ 60 years) enrolled in the SWOG S1826 study showed the Nivolumab-AVD regimen was better tolerated and improved progression free survival (PFS) compared to concurrent brentuximab vedotin-AVD (Bv-AVD). The sequential administration of Bv before and after AVD chemotherapy (seq Bv-AVD-Bv) is a commonly used approach to minimize the toxicity of Bv-AVD in older pts based on the tolerability and efficacy shown in a phase II study (Evens, et al. J Clin Oncol 2018). There is limited data on clinical outcomes with seq Bv-AVD-Bv in the real-world setting. We report our multicenter study of sequential Bv-AVD-Bv administration in older patients with cHL.

Methods:

This retrospective study included a total of 40 older pts with cHL treated with sequential Bv-AVD-Bv in 6 cancer centers. Descriptive statistics were used to depict patient demographics and disease characteristics prior to treatment initiation. Responses to therapy were assessed using the Lugano criteria. Response evaluable patients were those who received at least one cycle of chemotherapy with AVD. PFS and overall survival (OS) were estimated using log-rank testing with the Kaplan Meier curves.

Results:

The majority (n=23, 57.2%) of patients were male; median age was 72.5 years (range, 57-86 years); 10 (25%) pts were Hispanic, and 18 (45%) pts were Caucasian; performance status by ECOG was 0-2 in 33 (82.5%) pts. In terms of disease characteristics 19 (47.5%) pts had cHL NOS, 10 (25%) had nodular sclerosing subtype; stage III/IV in 35 (87.5%), stage II in 5 (12.5%) pts; B- symptoms in 21 (52.5%); extranodal disease in 19 (47.5%), with bone marrow involvement in 10 (25%) pts. Among the 38 response-evaluable patients the ORR and CR rates were 97.4% and 71.1%, respectively. Bv dose reductions or interruptions were reported in 14 (35.9%) pts. Treatment discontinuation (Td) occurred in 16 (40%) pts. The most common any grade adverse events were hematological toxicities (HT) in 28 (70%) pts and peripheral neuropathy in 24 (60%) pts. Forty-five percent of patients experienced grade 3 or higher HT. The overall incidence of grade 2 or higher peripheral neuropathy was 15%. The main reasons for treatment discontinuation were toxicity (n=9) and disease progression (n=4). During treatment, 1 (2.5%) pt reported loss of basic activities of daily living (ADLs) and 5 (12.5%) had loss of instrumental ADLs (iADLs). G-CSF prophylaxis was used in most (n=33, 82.5%) pts.

At a median follow up of 25.7 months (range, 2.6 - 58.9) the 2 years PFS was 62.6% (95% CI: 46.1-79.1) and the 2 years OS was 83.3% (95% CI: 67-99.6). On univariate analysis, the median PFS correlated with the depth of response (CR: not reached; PR: 11.4 months; SD/PD: 3.9 months; P=0.0001); and with treatment discontinuation (No Td: not reached; Td: 21.6 months; P=0.007). There was no correlation between age, sex, institution, B- symptoms, bone marrow involvement, ADL/iADLs, or disease stage with treatment discontinuation.

Conclusion:

Sequential Bv-AVD-Bv in older patients with cHL can help minimize the toxicity associated with the concurrent administration of Bv-AVD. This sequential approach has shown comparable efficacy in real-word setting as seen in clinical trials. Our findings suggest seq Bv-AVD-Bv remains a feasible option for older fit patients with cHL outside clinical trials. Further randomized studies in older cHL pts are needed.

Disclosures: Perez Perez: Kite Gilead: Speakers Bureau; AbbVie: Consultancy. Nahas: Janssen: Speakers Bureau; BMS: Speakers Bureau; Seagen: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Kareem: Pfizer: Consultancy; Janssen: Consultancy. Tobon: Eli Lilly: Consultancy, Honoraria, Other: Consultant/Advisory Board; Abbvie: Consultancy, Honoraria, Other: Consultant/Advisory Board; Bristol Myers Squibb: Consultancy, Honoraria, Other: Completed non-CE panel discussion. Rosenthal: RMEI, Curio Science, Targeted Oncology, OncLiveU: Other: Educational Workshop Speaker Role. Ansell: ADC Therapeutics: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Research Funding; Bristol Myers Squibb: Research Funding; Pfizer: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding; SeaGen: Research Funding; Takeda: Research Funding. Linhares: Celgene, Genentech, GSK, Incyte, Jansenn, Novartis, Seagen: Membership on an entity's Board of Directors or advisory committees; Kyowa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, ADC therapeutics, Alexion, AstraZeneca, BeiGene: Membership on an entity's Board of Directors or advisory committees. Alhaj Moustafa: AbbVie: Consultancy. Saeed: Abbvie: Consultancy; Pfizer: Speakers Bureau; Acrotech: Consultancy, Speakers Bureau; ADC therapeutics: Consultancy.

*signifies non-member of ASH