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PO.CL01.15 · 临床研究

Depth of immunoparesis predicts time to first therapy in newly diagnosed monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia

海报缩略图：Depth of immunoparesis predicts time to first therapy in newly diagnosed monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia
编号 1191 展板 15 时间 4/19 02:00–05:00 区域 Section 46 主讲 Yuan Yao, MD;MS
分会场 Prognostic Biomarkers 1
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作者与单位

Yuan Yao1, Kari G. Rabe2, Eli Muchtar1, Paul Hampel1, Yucai Wang1, Lindsey Roeker1, Saad Kenderian1, Amber Koehler1, Catherine Wagner1, Amy Behnken1, Jose F. Leis3, Mazie Tsang3, Talal Hilal3, Ricardo Daniel Parrondo4, Susan M. Schwager1, Min Shi5, Curtis A. Hanson5, Celine M. Vachon6, Shaji Kunnathu Kumar1, Esteban Braggio7, Neil E. Kay1, Susan Slager8, Sameer A. Parikh1

1Division of Hematology, Mayo Clinic, Rochester, MN,2Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN,3Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ,4Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL,5Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN,6Division of Epidemiology, Mayo Clinic, Rochester, MN,7Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, MN,8Division of Hematology; Division of Computational Biology, Mayo Clinic, Rochester, MN

摘要 Abstract

Background: Hypogammaglobulinemia at the time of CLL diagnosis predicts shorter time to first therapy (TTFT). However, the depth of immunoparesis and its impact on TTFT in newly diagnosed MBL/CLL remains unexplored. Methods: We identified previously untreated MBL/CLL patients from Mayo Clinic CLL Database (2000-2024) who had serum immunoglobulin (Ig; IgG, IgM and IgA) and monoclonal protein assessed within 1 year of diagnosis. Immunoparesis was evaluated: a) qualitatively by classifying patients into preserved, partial and full Ig suppression, based on the number of suppressed Igs; and b) quantitatively by calculating the average relative difference (ARD), defined as the mean percentage below normal for all Igs. For both methods, only uninvolved Igs were considered for those with monoclonal protein. TTFT was estimated by Kaplan-Meier with competing risk of death. Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 1420 patients, median age at diagnosis was 65 (range 28-96); 954 (67%) were male; 493 (44.8%) had unmutated IGHV , and 86 (6.8%) had TP53 disruption. The median [range, mg/dL] serum IgG, IgA, and IgM were 889 [111-5290], 132 [1-4880], and 49 [4-9480]. Low IgG was present in 472 (33.2%), low IgA in 223 (16.4%), and low IgM in 530 (37.3%) patients. An M-spike was detected in 122 (8.6%) patients; distribution was: IgG (73), IgM (30), IgA (6), or multiple (13). By qualitative assessment, preserved Ig were seen in 664 (46.8%), partial Ig suppression in 604 (42.5%), and full suppression in 152 (10.7%) patients. By quantitative assessment, median ARD was 0.6 (-0.8 to 11.3); 280 (19.7%) patients had negative ARD, and 1140 (80.3%) had positive ARD. In those with negative ARD, 128 (9%) had partial Ig suppression and 152 (10.7%) had full Ig suppression; in those with positive ARD, 664 (46.8%) had preserved Ig and 476 (33.5%) had partial Ig suppression. Median follow-up was 14.7 years; 510 patients progressed requiring therapy. Median TTFT was 9.6 years. Median TTFT for patients with preserved Ig was 12.6 years, 8.0 years for partial Ig suppression (HR 1.4, 95%CI 1.1-1.7), and 1.8 years for full Ig suppression (HR 3.1, 95%CI 2.4-4.0). The median TTFT was 2.3 and 12.1 years for patients with negative vs positive ARD; negative ARD was associated with shorter TTFT (HR 2.4, 95%CI 2.0-2.9). After adjusting for sex and CLL-International Prognostic Index (CLL-IPI) score, full Ig suppression (HR 2.9, 95%CI 2.2-3.9) and partial Ig suppression (HR 1.6, 95% CI 1.3-2.0) were associated with shorter TTFT (model 1, c-stat 0.77); and negative ARD (HR 2.4, 95%CI 2.0-2.9) was associated with shorter TTFT (model 2, c-stat 0.76). Negative ARD identified an additional 9% of patients at higher risk for shorter TTFT beyond full Ig suppression. Conclusions: The depth of immunoparesis at diagnosis predicts TTFT and enhances risk stratification in newly diagnosed MBL/CLL.
利益披露 Disclosure
Y. Yao, None.. K. G. Rabe, None.. E. Muchtar, None. P. Hampel, BeOne Medicines Ltd, Research Funding ), . AbbVie, Consultancy (Includes expert testimony) ). AstraZeneca, Research Funding ). Y. Wang, Morphosys, Research Funding ). Merck, Research Funding ). Novartis, Research Funding ). Loxo/Eli Lily, Consultancy (Includes expert testimony), Loxo/Eli Lily, Consultancy (Includes expert testimony) ). InnoCare, Consultancy (Includes expert testimony) InnoCare, Research Funding ). Abbvie, Consultancy (Includes expert testimony) Abbvie, Research Funding ). Genmab, Consultancy (Includes expert testimony) Genmab, Research Funding ). Genentech, Research Funding ). Kite, Consultancy (Includes expert testimony) ). Incyte, Consultancy (Includes expert testimony) Incyte, Research Funding ). L. Roeker, AbbVie: Consultancy; Research Funding ). Abbott Laboratories: Current equity holder (publicly traded) Other, Abbott Laboratories: Current equity holder (publicly traded). Adaptive Biotechnologies: Research Funding ). Aptose Biosciences: Research Funding ). Ascentage Pharma: Consultancy ). AstraZeneca: Consultancy; Research Funding ). BeiGene: Consultancy ). Curio: Consultancy ). DAVA: Consultancy ). Dren Bio: Research Funding ). Genentech: Research Funding ). Janssen: Consultancy ). Loxo Oncology: Consultancy; Research Funding ). Medscape: Consultancy ). PeerView: Consultancy ). Pfizer: Consultancy; Research Funding ). Pharmacyclics: Consultancy ). Qilu Puget Sound Biotherapeutics: Research Funding ). TG Therapeutics: Consultancy ). S. Kenderian, BMS: Consultancy; Research Funding ). Capstan Bio: Consultancy ). Carisma: Consultancy ). Chymal: Equity (private company) Other, Chymal: Equity (private company). Chymal Therapeutics: Patents/Royalties Other Intellectual Property. Gilead: Consultancy; Research Funding ). Humanigen: Consultancy; Patents/Royalties; Research Funding ), Other Intellectual Property. Humanigen/Taran: Patents/Royalties Other Intellectual Property. Immix Bio: Patents/Royalties Other Intellectual Property. Juno: Consultancy; Research Funding ). Juno/BMS: Consultancy ). Kite: Consultancy; Research Funding ). Lentigen: Research Funding ). LifeEngine Animal Health Laboratories Inc: Research Funding ). Luminary: Consultancy ). MorphoSys: Research Funding ). MustangBio: Patents/Royalties Other Intellectual Property. Novartis: Consultancy; Patents/Royalties; Research Funding ), Other Intellectual Property. Sunesis/Viracta: Research Funding ). Tolero: Research Funding ). A. Koehler, None.. C. Wagner, None.. A. Behnken, None.. J. F. Leis, None. M. Tsang, Genentech, Inc.: Consultancy ). Lilly: Research Funding ). ONO: Research Funding ). Poseida Therapeutics: Current equity holder (publicly traded) Other, Poseida Therapeutics: Current equity holder (publicly traded). T. Hilal, None. R. D. Parrondo, AbbVie – Consultancy; Research Funding ). Aptitude Health – Honoraria Other, Aptitude Health – Honoraria. AstraZeneca – Consultancy; Honoraria ). BeOne Medicines – Honoraria; Research Funding ). BeiGene/BeOne – Consultancy; Research Funding ). Cullinan Therapeutics – Research Funding ). GlaxoSmithKline – Research Funding ). Janssen – Consultancy ). Loxo Oncology/Lilly – Consultancy ). Mashup Media LLC – Honoraria Other, Mashup Media LLC – Honoraria. MJH Life Sciences / Intellisphere LLC – Honoraria Other, MJH Life Sciences / Intellisphere LLC – Honoraria. Nurix Therapeutics – Research Funding ). Philips Group Oncology Communications – Honoraria Other, Philips Group Oncology Communications – Honoraria. Precisca / Ultimate Opinions in Medicine – Honoraria Other, Precisca / Ultimate Opinions in Medicine – Honoraria. Sanofi Aventis – Consultancy; Honoraria ). S. M. Schwager, None.. M. Shi, None.. C. A. Hanson, None.. C. M. Vachon, None. S. K. Kumar, AbbVie, Consultancy (Includes expert testimony) AbbVie, Research Funding ). Sanofi, Consultancy (Includes expert testimony) ). Adaptive, Consultancy (Includes expert testimony) Adaptive, Research Funding ). Novartis, Consultancy (Includes expert testimony) ). Takeda, Consultancy (Includes expert testimony) Takeda, Research Funding ). Merck, Consultancy (Includes expert testimony) ). Oncopeptides, Consultancy (Includes expert testimony) ). Roche, Consultancy (Includes expert testimony) ). Janssen, Consultancy (Includes expert testimony) Janssen, Research Funding ). MedImmune/AstraZeneca, Consultancy (Includes expert testimony) MedImmune/AstraZeneca, Research Funding ). Celgene, Consultancy (Includes expert testimony) Celgene, Research Funding ). KITE, Consultancy (Includes expert testimony) KITE, Research Funding ). E. Braggio, None. N. E. Kay, AbbVie: Research Funding ). Acerta Pharma: Research Funding ). AstraZeneca: Consultancy; Research Funding ). Beigene: Consultancy ). Bristol Myers Squibb / Celgene: Consultancy ). Dren Bio: Consultancy ). Janssen: Consultancy; Research Funding ). Merck: Research Funding ). Pharmacyclics: Consultancy; Research Funding ). S. Slager, None. S. A. Parikh, AstraZeneca – Consultancy, Honoraria, Research Funding ). BeOne Medicines Ltd – Consultancy, Honoraria ). Genentech – Consultancy, Honoraria, Research Funding ). Janssen – Consultancy, Honoraria, Research Funding ). Kite Pharma – Consultancy, Honoraria ). Merck – Consultancy, Honoraria, Research Funding ). MingSight Pharmaceuticals – Consultancy, Honoraria ). Novalgen Limited – Consultancy, Honoraria ). Pharmacyclics – Consultancy, Honoraria ). So Bi – Consultancy, Honoraria ).

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