Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Population data for Aggressive NHL Management
Hematology Disease Topics & Pathways:
Clinical Trials, Non-Hodgkin Lymphoma, Lymphomas, Clinical Research, B Cell Lymphoma, Diseases, Aggressive Lymphoma, Lymphoid Malignancies, Molecular Testing
Methods: Eligible pts with DLBCL or high-grade B-cell lymphoma (HGBCL) who received anthracycline-containing chemotherapy were enrolled across five cancer centers. In pts who achieved a PET-negative CR, serial peripheral blood samples were obtained every 3 months (mos) and CT scans every 6 mos for 2 years (yrs) post-treatment. The IS MRD assay (Adaptive Biotechnologies, Seattle, WA) that leverages multiplex PCR followed by NGS to identify and track rearrangements of IgH, V-J, D-J and IgK/L loci and translocations in Bcl1/2-IgH was used. MRD positive was defined as any detectable rearrangement and MRD undetectable as no evidence of rearrangement.
Results: 500 pts were enrolled and 400 were evaluable (pre-treatment tumor pathology available, completed frontline treatment, and achieved PET-negative CR at end-of-treatment). Baseline characteristics were median age of 62 yrs (range 19-95), male sex 58%, advanced stage 61%, and poor-risk by R-IPI 42%. Histologies included DLBCL, NOS (88%), primary mediastinal B-cell lymphoma (6%), HGBCL (5%), T-cell rich B-cell lymphoma (3%), and other (1%). Pts received regimens including RCHOP x 6 cycles (37%), REPOCH x 6 cycles (20%), clinical trial (15%), combined modality therapy (RCHOP+RT) (9%), and other RCHOP variations (19%).
Among the 400 evaluable pts, 44 relapses have occurred as of July 1, 2021. In 45% of pts (20/44), clinical relapse was detected using surveillance imaging alone (typically CT CAP with IV contrast) in an otherwise asymptomatic pt with a normal physical exam and laboratory evaluation. In 10% of pts (4/44), relapse was detected by patient-reported clinical symptoms alone. In 45% of pts (20/44), relapse was detected by imaging, clinical symptoms, and/or evaluation by an oncologist. With a median follow-up of 34 months, the 2-year PFS was 88.9% (85.8, 92.1). Advanced age, advanced stage, and poor-risk R-IPI were associated with inferior PFS.
Of the 44 relapses, tumor-specific clonotypes were identified in 39 pts (4 failed quality control (QC), 1 failed calibration) and 38 pts had ≥1 sample available within 90 days of relapse. Of 356 patients in ongoing CR, tumor-specific clonotypes were identified in 279 patients (29 failed QC, 33 failed calibration, and 15 are pending sequencing). The patient-level prospective MRD results are shown in Figure 1. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the IS MRD assay was 63% (24/38), 78% (218/279), 28% (24/85), and 94% (218/232), respectively. Plasma MRD detection had improved sensitivity and specificity compared with circulating cells. Among the 24 relapsed patients with a positive MRD result at or before relapse, the median anticipation of the test was 3 months (range 0 to 24 months).
Conclusion: Overall outcomes are excellent for DLBCL and HGBCL pts who achieve PET-negative CR. In this multicenter prospective analysis with standardized follow up, a substantial proportion (45%) of clinical relapses are detected radiographically in asymptomatic pts, supporting the value of CT surveillance imaging in DLBCL, particularly for pts with advanced stage or high-risk disease. MRD assessment using the IS MRD assay had suboptimal sensitivity and specificity in the post-treatment surveillance setting in DLBCL. Further study of the clinical context and its correlation with test performance is ongoing.
Disclosures: Kumar: Kite Pharmaceuticals: Other: advisory board , Research Funding; Abbvie Pharmaceuticals: Research Funding; Celgene: Honoraria, Other: advisory board, Research Funding; Adaptive Biotechnologies, Celgene, Abbvie Pharmaceticals, Pharmacyclics, Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Astra Zeneca: Honoraria, Other: Advisory Board, Research Funding; Seattle Genetics: Research Funding. Westin: Bristol Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Morphosys: Research Funding; Novartis: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Umoja: Consultancy; 47 Inc: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; Curis: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Schuster: TG Theraputics: Research Funding; Incyte: Research Funding; Adaptive Biotechnologies: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Loxo Oncology: Consultancy; Juno Theraputics: Consultancy, Research Funding; BeiGene: Consultancy; Alimera Sciences: Consultancy; Acerta Pharma/AstraZeneca: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Abbvie: Consultancy, Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Janssen: Consultancy, Honoraria; NCI: Research Funding; University of Miami: Current Employment; NIH grants: Research Funding; Stanford University: Patents & Royalties; Verastem: Consultancy, Honoraria. Jacob: Adaptive Biotechnologies: Current Employment. Mullins: Adaptive Biotechnologies: Current Employment. Zelenetz: AstraZeneca: Honoraria; Amgen: Honoraria; Beigene: Honoraria, Other, Research Funding; Gilead: Honoraria, Research Funding; SecuraBio: Honoraria; Genentech/Roche: Honoraria, Research Funding; BMS/Celgene/JUNO: Honoraria, Other; Janssen: Honoraria; LFR: Other; MEI Pharma: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Verastem: Honoraria; MethylGene: Research Funding; NCCN: Other; Pharmacyclics: Honoraria; Novartis: Honoraria; Gilead: Honoraria; MorphoSys: Honoraria.
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