Abstract
BACKGROUND:
T-cell/histiocyte-rich large B-cell lymphoma (T/HRLBCL) is an aggressive morphological variant of diffuse large B cell lymphoma (DLBCL), which often presents with advanced stage disease, extra-nodal involvement, an association with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and has poor outcomes compared to patients (pts) with other DLBCL subtypes.
METHODS:
We conducted a retrospective, single institution study of pts with newly diagnosed T/HRLBCL and reviewed demographic variables, clinical and pathological characteristics, treatment patterns and outcomes. Pts who were treated/ referred to MD Anderson Cancer Center from 2005-2020 were included in the analysis. We excluded cases without pathologic confirmation by a hematopathologist, missing treatment information, lack of appropriate follow up, or previous treatment with anthracycline containing chemotherapy for unrelated diagnosis. Fisher's exact test or Chi-square test was used to evaluate the association between two categorical variables, Kaplan-Meier method used to estimate the time-to-event endpoints including progression free survival (PFS) and overall survival (OS).
RESULTS:
A total of 172 patients were reviewed, 65 pts were excluded due to aforementioned reasons. A total of 107 newly diagnosed patients met morphological diagnostic criteria. Seventy four pts (70%) were less than 60 years of age at diagnosis with median age of 49 (18-89 years). Seventy two were male (68%) and 37 pts (34%) had documented NLPHL prior to or at the time of T/HRLBCL diagnosis. Ninety pts (89%) were diagnosed with advance stage disease (stage 3/4) with 59pts (55%) with ≥ 1 extra nodal site. Thirty-seven pts (35%) had associated splenomegaly and/or FDG avid splenic involvement. Common extra nodal sites included bone (26%), bone marrow (19%) and liver (17%). On univariate analysis for survival outcomes, there was not a statistical significant association with any of the following: age, gender, association with NLPHL, presence of B symptoms, performance status, elevated lactate dehydrogenase, extra nodal sites, spleen involvement/ splenomegaly, involvement of liver, and type of front-line treatment.
Majority of patients (73%) received front line treatment with R-CHOP, followed by Dose Adjusted R-EPOCH (15%) and other regimens in 11%. Central nervous system prophylactic therapy was given in 24 pts (intrathecal) and 3 pts (high dose methotrexate). One pt had an autologous stem cell transplant consolidation as part of frontline treatment. Seventy (69%) pts achieved complete response (CR), with an overall response rate of 75%, and 25 pts progressed on frontline treatment.
Complete remission rates were higher with R-EPOCH (81%) than RCHOP (70%) (p=0.57), with 2 year PFS to first line treatment at 38% and 46% respectively (P=0.20). In the whole cohort, 2-year PFS was 48% and 2-year OS was 83%. Of the 53 patients who relapsed, 48 patients received salvage chemotherapy, 26 pts went on to receive high dose chemotherapy and autologous transplant, and only 4 patients relapsed after transplant. Three patients in the whole cohort who received CD19 CAR-T and all 3 had disease progression.
Conclusions: This study demonstrates the generally poor outcomes in pts with T/HRLBCL despite the use of monoclonal antibodies and intensive cytotoxic therapies. T/HRLBCL remains a high unmet need for novel therapies.
Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Steiner: BMS: Research Funding; Rafael Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy. Chihara: Astrazeneca: Honoraria. Jain: kite: Consultancy; Lilly: Consultancy. Flowers: Morphosys: Research Funding; Ziopharm: Research Funding; Pfizer: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Kite: Research Funding; EMD: Research Funding; Xencor: Research Funding; Cellectis: Research Funding; SeaGen: Consultancy; BeiGene: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Spectrum: Consultancy; Genentech/Roche: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Allogene: Research Funding; Denovo: Consultancy; Biopharma: Consultancy; Epizyme, Inc.: Consultancy; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Nektar: Research Funding; Amgen: Research Funding; Adaptimmune: Research Funding; National Cancer Institute: Research Funding; Guardant: Research Funding; Sanofi: Research Funding; Novartis: Research Funding; TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Iovance: Research Funding; 4D: Research Funding; Bayer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics: Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Nastoupil: IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Epizyme: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ADC Therapeutics: Honoraria; TG Therapeutics: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; MorphoSys: Honoraria; Gilead/Kite: Honoraria, Research Funding; Bayer: Honoraria; Genentech: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Janssen: Honoraria, Research Funding. Wang: Celgene: Research Funding; Loxo Oncology: Consultancy, Research Funding; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Clinical Care Options: Honoraria; VelosBio: Consultancy, Research Funding; BioInvent: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; CAHON: Honoraria; Moffit Cancer Center: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Mumbai Hematology Group: Honoraria; Epizyme: Consultancy, Honoraria; Hebei Cancer Prevention Federation: Honoraria; Chinese Medical Association: Honoraria; Dava Oncology: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding; Molecular Templates: Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Lilly: Research Funding; Newbridge Pharmaceuticals: Honoraria; OMI: Honoraria; Physicians Education Resources (PER): Honoraria; Pharmacyclics: Consultancy, Research Funding; Scripps: Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Oncternal: Consultancy, Research Funding; BGICS: Honoraria; Bayer Healthcare: Consultancy; CStone: Consultancy; DTRM Biopharma (Cayman) Limited: Consultancy; Genentech: Consultancy; InnoCare: Consultancy, Research Funding; Juno: Consultancy, Research Funding. Vega: i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology: Research Funding; CRISPR Therapeutics and Geron: Research Funding. Iyer: CRISPRX: Research Funding; Seattle Genetics: Research Funding; Rhizen: Research Funding; Merck: Research Funding; Legend: Research Funding; Innate: Research Funding; Spectrum: Research Funding; Trillium: Research Funding; Astra Zeneca: Research Funding; Yingli: Research Funding; Cyclacel: Research Funding. Westin: Morphosys: Research Funding; 47 Inc: Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Curis: Research Funding; Genentech: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; Umoja: Consultancy; ADC Therapeutics: Consultancy, Research Funding.
