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5099 Hodgkin Lymphoma Transformation in Patients Who Received No Prior Chemotherapy for CLL/SLL: Outcomes from a Multicenter Retrospective Study in the Modern Era of Therapy

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, Hodgkin lymphoma, CLL, Lymphomas, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Paul J. Hampel, MD1, Ying Huang, MS, MA2, Sarah Miller, BS3*, John N. Allan, MD4, Seema A Bhat, MD5, David A. Bond, MD, BS5, Danielle M. Brander, MD6, John C. Byrd, MD7, Julio C. Chavez, MD8, Elise A. Chong, MD9, Alexey Danilov, MD, PhD10, Matthew S. Davids, MD, MMSc11, Kaitlyn M. Dvorak-Kornaus, PhD5*, Hannah Freedman, RN12*, Nikita Malakhov, MD13, Matthew Matasar, MD, MS14, Cecelia Miller, PhD15, Sameer A. Parikh, MBBS16, Erin M. Parry, MD, PhD17, Kari G. Rabe, MS18*, Phil Raess, MD, PhD19*, Manoj Rai, MD20*, Joanna M. Rhodes, MD21, Kerry A. Rogers, MD5, Aditi Saha, MBBS22, Jake Schade, BA23*, Geoffrey Shouse, PhD, DO24, Stephen E Spurgeon, MD25, Deborah M. Stephens, DO26, Yucai Wang, MD, PhD16, Jennifer A. Woyach, MD27, Max Yano, MD, PhD28*, Omer Zulfa29* and Adam S Kittai, MD30

1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
2Division of Hematology, Department of Statistics, The Ohio State University Wexner Medical Center, Columbus, OH
3Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
4Division of Hematology and Oncology, Weill Cornell Medicine, Long Island City, NY
5Division of Hematology, The Ohio State University, Columbus, OH
6Duke University, Durham, NC
7Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
8Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
9Department of Medicine, Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
10City of Hope Comprehensive Cancer Center, La Canada Flintridge, CA
11Department of Medical Oncology, Dana-Farber Cancer Institute, Inc., Boston, MA
12Department of Medical Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA
13Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY
14Division of Blood Disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, New York, NY
15Division of Pathology, The Ohio State University, Columbus, OH
16Division of Hematology, Mayo Clinic, Rochester, MN
17Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
18Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
19Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, OR
20Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland, OR
21Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
22Department of Hematology/Oncology, Moffitt Cancer Center, West Orange, NJ
23Rutgers Cancer Institute, New Brunswick, NJ
24City of Hope Cancer Center, Duarte, CA
25Knight Cancer Institute, Oregon Health & Science University, Portland, OR
26University of North Carolina Chapel Hill, Chapel Hill, NC
27Division of Hematology, Ohio State University Comprehensive Cancer Center, Columbus, OH
28College of Medicine, The Ohio State University, Columbus, OH
29University of Cinncinati, Cincinatti, OH
30Icahn School of Medicine at Mount Sinai, New York, NY

Introduction:

Richter transformation is the development of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma, in patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Transformation into Hodgkin lymphoma (HT) is a rare event and outcomes in pts with this complication in the current CLL/SLL therapeutic era of small molecule inhibitors (SMI; e.g., Bruton tyrosine kinase inhibitors [BTKi] and BCL2 inhibitors [BCL2i]) are unknown.

Methods:

We conducted a retrospective study of pts from 12 academic centers. Pts with HT who had not previously received chemotherapy for CLL/SLL-directed treatment (tx) were included. Pt, disease, and tx characteristics were collected. HT was categorized into 3 groups: “Concurrent HT,” defined as HT and CLL/SLL diagnosed simultaneously (within 3 months); “HT without prior CLL/SLL tx,” defined as HT and CLL/SLL diagnosed >3 months apart with the CLL/SLL never treated; and “HT with prior non-chemotherapy tx for CLL/SLL” defined as having received non-chemotherapy CLL/SLL-directed tx prior to the diagnosis (dx) of HT. Overall survival (OS) was measured from HT dx and estimated using the Kaplan-Meier method. Cox regression model was used to identify prognostic factors associated with OS.

Results:

Within a total cohort of 402 pts with Richter transformation (all histologies) without prior chemotherapy, 41 pts with HT (10%) were identified: 12 with concurrent HT, 10 with HT without prior CLL/SLL tx, and 19 with HT with prior non-chemotherapy tx for CLL/SLL. The median age at CLL/SLL dx was 62 years (range 31-96 years) and 73% were male. At CLL/SLL dx, 67% (14/21 evaluated) had unmutated IGHV, and 24% (8/34 evaluated) had TP53 disruption (del(17p) and/or TP53 mutation).

The median age at HT dx was 65 years (range 31-96 years) among all pts. At HT dx, there was no significant difference in highest SUV on PET (median 12.3, range 3-31.1), lactate dehydrogenase (LDH) level (median 242 U/L, range 112-859 U/L), or lymph node longest diameter (median 4.6 cm, range 1.6-25 cm) among the 3 subgroups.

The median time from CLL/SLL dx to HT dx was 5.4 years (range 0.3-16.5 years) in pts with HT without prior CLL/SLL tx and 4.2 years (range 0.5-17.3 years) in pts with HT with prior non-chemotherapy tx for CLL/SLL. The median number of prior non-chemotherapy CLL/SLL-directed tx was 1 (range 1-6) and included BTKi only (n=17) and BTKi and BCL2i sequentially (n=2); no patient had received only prior BCL2i. Among the 19 pts with HT with prior non-chemotherapy tx for CLL/SLL, 18 pts were on active tx at time of dx (17 BTKi, 1 BCL2i).

Initial HT management included: doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; n=16), brentuximab vedotin (BV)-AVD (n=10), radiation only (n=2), other systemic tx (n=11), and supportive cares / hospice (n=2). All but 1 of the 11 other systemic tx were various HL tx regimens. Across all pts with available data (n=32), the overall response rate to 1st line HT tx was 78% (69% complete response rate); 13% had progressive disease and 9% (n=3; all with concurrent HT) died within 6 months without formal response assessment. A total of 11 pts received at least 1 additional line of therapy for HT, which included BV (n=4), an immune checkpoint inhibitor (n=1), or both (n=6) at any point beyond 1st line HT tx.

Median follow-up from HT dx was 32.8 months (range 2.4-253.8 months). The 36-month OS for the entire cohort was 75% (95% CI: 55-87%). The 36-month OS estimates by subgroups were: 62% (95% CI: 26-84%) in pts with concurrent HT, 100% in pts with HT without prior CLL/SLL tx (no events by 36 months), and 67% (95% CI: 33-87%) in pts with HT with prior non-chemotherapy tx for CLL/SLL.

Exploratory univariable analysis identified TP53 disruption at CLL dx (HR 12.36; 95% CI: 2.55-59.84) and lymph node longest diameter (HR 1.32 per 1 cm increase; 95% CI: 1.12-1.55) and LDH 2-fold increase (HR 3.97; 95% CI 1.24-12.68) at HT dx as prognostic for worse OS. HT subgroup was not prognostic.

Conclusions:

This is the largest report of outcomes in pts with CLL/SLL who develop HT following SMI tx without any prior chemotherapy, representing a contemporary cohort. Prior CLL/SLL tx status was not associated with OS; however, cautious interpretation is required given the sample size. Our findings support the use of appropriate HL-directed treatment in the setting of HT; however, OS estimates remain worse than would be expected in an older adult de novo HL cohort (Cheng Blood Adv 2022).

Disclosures: Allan: ADC Therapeutics: Consultancy; TG Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Research Funding; Epizyme: Consultancy; BeiGene: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Bhat: AstraZeneca: Consultancy, Research Funding. Bond: Incyte: Research Funding; BMS: Research Funding; Kite/Gilead: Research Funding; GenMab: Research Funding; ADC Therapeutics: Consultancy; AstraZeneca: Research Funding; Nurix Therapeutics: Consultancy, Research Funding; Accutar: Research Funding; Novartis: Consultancy, Research Funding. Brander: BeiGene: Consultancy, Other: site PI clinical trial (grant paid to institution); Catapult: Other: site PI clinical trial (grant paid to institution); DTRM: Other: site PI clinical trial (grant paid to institution); Genentech: Consultancy, Other: site PI clinical trial (grant paid to institution); Juno/Celegene/BMS: Other: site PI clinical trial (grant paid to institution); NeWave: Other: site PI clinical trial (grant paid to institution); Nurix: Other: site PI clinical trial (grant paid to institution); Pharmacyclics: Consultancy, Other: site PI clinical trial (grant paid to institution); TG therapeutics: Other: site PI clinical trial (grant paid to institution); BMS: Other; AstraZeneca/Acereta: Other: site PI clinical trial (grant paid to institution); ArQule/Merck: Other: site PI clinical trial (grant paid to institution); AbbVie: Consultancy, Other: site PI clinical trial (grant paid to institution). Chavez: Janssen: Honoraria; Lilly: Honoraria, Speakers Bureau; AstraZeneca: Consultancy; Cellectis: Consultancy; GenMab: Consultancy, Research Funding; Abbvie: Consultancy; Allogene: Consultancy; Kite, a Gilead Company: Consultancy; Novartis: Consultancy; BeiGene: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy; Merck: Research Funding. Chong: AstraZeneca: Consultancy, Research Funding; Nurix: Research Funding; Genentech/Roche: Research Funding; CARGO: Research Funding; AbbVie: Research Funding; Beigene: Consultancy; Genmab: Research Funding. Danilov: Cyclacel: Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; ADCT: Consultancy; MEI Pharma: Research Funding; Takeda: Research Funding; Bayer: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Incyte: Consultancy; MorphoSys: Consultancy; Nurix: Consultancy, Research Funding; Genentech: Consultancy; BeiGene: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy, Research Funding; GenMab: Consultancy, Research Funding; Janssen: Consultancy. Davids: Ascentage Pharma: Consultancy, Research Funding; Adaptive Biosciences: Consultancy; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Genmab: Consultancy; Merck: Consultancy; Surface Technology: Research Funding; BMS: Consultancy; MEI Pharma: Research Funding; Novartis: Research Funding; Janssen: Consultancy; AbbVie: Consultancy, Research Funding; Eli Lilly: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding. Matasar: Seattle Genetics: Consultancy, Honoraria, Research Funding; Kite: Honoraria; Pfizer: Honoraria; GM Biosciences: Consultancy, Research Funding; Merck: Current equity holder in publicly-traded company; Genentech: Consultancy, Honoraria, Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees; Allogene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Immunovaccine Technologies: Research Funding; IMV Therapeutics: Honoraria; Takeda: Honoraria; Regeneron Pharmaceuticals, Inc.: Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; BMS/Celgene: Honoraria; ADC Therapeutics: Honoraria; AstraZeneca: Honoraria; Bayer: Consultancy, Honoraria, Research Funding. Parikh: Merck: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MingSight: Consultancy; Amgen: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy; Novalgen Limited: Consultancy; Genentech: Consultancy, Research Funding; BeiGene: Consultancy; Janssen: Consultancy, Research Funding; AbbVie: Consultancy. Rogers: Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees; AstraZeneca Pharmaceuticals LP.: Membership on an entity's Board of Directors or advisory committees; AbbVie Inc, BeiGene Ltd, Genentech, a member of the Roche Group, Janssen Biotech Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Pharmacyclics LLC, an AbbVie Company: Consultancy; AbbVie Inc, Genentech, a member of the Roche Group, Novartis: Research Funding. Shouse: Abbvie: Consultancy; Astra Zeneca: Honoraria; Beigene, Inc: Consultancy, Honoraria, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau. Stephens: AstraZeneca, Beigene, Novartis: Research Funding; Abbvie, AstraZeneca, Beigene, BMS, Celegene, Eli Lilly, Genentech, Janssen, Pharmacyclics: Consultancy. Wang: Kite: Honoraria; Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; InnoCare, AbbVie: Consultancy; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding. Woyach: AbbVie: Research Funding; Pharmacyclics: Consultancy, Research Funding; Schrodinger: Research Funding; AstraZeneca: Consultancy; BeiGene: Consultancy; Loxo Lilly: Consultancy; Merck: Consultancy; Janssen: Research Funding; Morphosys: Research Funding; Newave: Consultancy; Genentech, Inc.: Consultancy. Kittai: Galapagos: Consultancy; Abbvie: Consultancy; BMS: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy, Research Funding, Speakers Bureau; Eli-Lilly: Consultancy.

*signifies non-member of ASH