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476 Real World (RW) Outcomes and Prognostication of Older Patients with Primary Central Nervous System Lymphoma (PCNSL) in the Contemporary Era

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: PCNSL Treatment and Prognosis and CNS Prophylaxis in High-Risk Aggressive Lymphomas
Hematology Disease Topics & Pathways:
Diseases, Elderly, Non-Hodgkin Lymphoma, CNS Lymphoma, Lymphoid Malignancies, Study Population, Clinically relevant
Sunday, December 6, 2020: 2:00 PM

Kevin A. David, MD 1, Suchitra Sundaram, MD2*, Seo-Hyun Kim, MD3, Ryan Vaca, MD4, Yong Lin, PhD1*, Samuel Singer, MD5*, Mary-Kate Malecek, MD6, Jordan Carter, MD1*, Adam Zayac, MD7, Myung Sun Kim, MD8*, Nishitha Reddy, MD9, Alma Habib, MD10*, Christopher Strouse, MD11, Jerome Graber, MD12*, Veronika Bachanova, MD, PhD13, Mazie Tsang, MD14, Ajay Major, MD, MBA15, David A. Bond, MD, BS16, Prashasti Agrawal17*, Angel Mier-Hicks, MD18, Pallawi Torka, MD19, Priya Rajakumar, MD20*, Parameswaran Venugopal, MD21, Michael Glantz, MD, PhD22*, Samuel Goldlust, MD23*, Rahul Matnani, MD24*, Pallavi Kumar, MD25*, Thomas A Ollila, MD26, Johnny Cai, DO27*, Stephen E. Spurgeon, MD28, Alex G Sieg, MD, MS29*, Joseph Cleveland, MD30*, Narendranath Epperla, MD, MS31, Reem Karmali, MD, MSc32, Seema Naik, MD33*, Peter Martin, FRCPC, MD, MS34, Sonali M. Smith, MD35, James L. Rubenstein, MD, PhD14, Brad S. Kahl, MD36 and Andrew M. Evens, DO, MMSc1

1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
2Roswell Park, Buffalo, NY
3Rush University Medical Center, Chicago, IL
4Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA
5John Theurer Cancer Center, Hackensack, NJ
6Department of Medicine, Washington University School of Medicine, University City, MO
7Department of Medicine, Alpert Medical School of Brown University, Providence, RI
8Knight Cancer Institute, Oregon Health and Science University, Portland, OR
9Vanderbilt University Medical Center, Nashville, TN
10University of Minnesota School of Medicine, Minneapolis, MN
11Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
12University of Washington, Seattle, WA
13Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
14Hematology/Oncology, UCSF, San Francisco, CA
15Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
16Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
17Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY
18Roswell Park Comprehensive Cancer Center, Buffalo, NY
19Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY
20Division of Hematology, Oncology and Stem Cell Transplant, Rush University Medical Center, Chicago, IL
21Division of Hematology Oncology, Rush University Medical Center, Chicago, IL
22Department of Neurosurgery, Penn State College of Medicine, Hershey, PA
23John Theurer Cancer Center, Hackensack-Meridian Health, Hackensack, NJ
24Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
25Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
26Brown University, Providence, RI
27Oregon Health and Science University, Portland, OR
28Oregon Health & Science University, Portland, OR
29Department of Internal Medicine, University of Iowa, Iowa City, IA
30University of California, San Francisco, San Francisco, CA
31The Ohio State University James Comprehensive Cancer Center, Columbus, OH
32Division of Hematology Oncology, Northwestern University, Chicago, IL
33Penn State Cancer Institute, Penn State Hershey Medical Center, Hershey, PA
34Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY
35Department of Oncology, University of Chicago, Chicago, IL
36Washington University School of Medicine in St. Louis, Saint Louis, MO

Introduction: Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and complexities with delivery of chemotherapy (CT). The optimal induction CT and consolidation regimens for older PCNSL pts is unknown. Moreover, there are few large scale prognostication studies available, including analysis of geriatric assessments (GA). We analyzed detailed characteristics, treatment patterns and outcomes with prognostication across 17 academic centers.

Methods: We conducted a large, RW retrospective study of newly diagnosed PCNSL pts (1/2008-1/2019) ages ≥ 60 years (yrs). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. We detailed Cumulative Index Rating Scale-Geriatric (CIRS-G) scores & other GAs. Univariate associations were derived via Cox model with variables p<0.05 entered stepwise into a multivariate (MVA) model.

Results: Among 491 initial cases, n=450 cases were verified for diagnosis & follow-up. Clinical features included: median age 71 yrs (60-88); male 47%; elevated LDH 30%; creatinine clearance <60 ml/min in 20% (median 81 ml/min); hemoglobin <10 g/dL in 8%; and albumin <3.5 g/dL in 35%. 21% of pts had prior or concurrent malignancy and 7% had history of solid organ transplant or autoimmune disease. Histology was DLBCL in 96% (COO non-GC in 76%) with CD20 expression seen in 98%. Immunohistochemistry showed MYC & BCL2 double expression in 40%; EBER was noted in 10% of pts (3/4 being PTLD pts). For disease location, brain parenchyma was involved in 94% of pts with 46% having a single site (54% >1 site). Cerebral involvement predominated in 75% with deep structure involvement in 20% & cerebellum in 5%. CSF involvement was documented in 13% of pts (unchecked in 26%). For GA at diagnosis, the median CIRS-G score was 6 (range 0-27) and impaired self-care activities of daily living (ADLs) were noted in 36%. Furthermore, geriatric syndrome (ie, dementia, delirium, depression, and/or falls) was present in 45% of pts.

Induction therapy included CT in 91% of pts (of whom 82% had rituximab (Rtx)) and radiation therapy (RT) in 8%. The most common chemotherapy regimens were: high-dose methotrexate (HD MTX) or HD MTX with Rtx (MR) in 38%; HD MTX/procarbazine/vincristine (MPV) +/- Rtx 30%; HD MTX/temozolomide/Rtx (MTR) 22%; Rtx alone 2%; and HD MTX/cytarabine/thiotepa/Rtx (MATRIX) in 2%. Median MTX dosing for all pts was 3.5 g/m2 (range 1-8 g/m2), and by 3 most common regimens (all g/m2): MTR 5.1; MR 5.4; MPV 3.1 (P<.0001). For response to induction, 60% had complete response (CR), 18% partial response (PR), 6% stable disease & 16% had primary refractory disease. Induction CT was stopped due to toxicity in 21% of pts and the treatment-related mortality was 7%. Among 321 pts with CR or PR, 14% had autologous stem cell transplant (ASCT); 25% received consolidative CT; and 5% had RT. The most common CT maintenance regimens were temozolomide (n=22), lenalidomide (n=20) and HD MTX (n=15). Among pts experiencing relapse or progression, the most common 2nd line therapies were RT (n=40), MTX (n=39), temozolomide (n=14) and MTR (n=10); 2 pts ultimately went on to receive ASCT.

With 42 month median follow-up (1-125), 3-yr PFS & OS for all pts were 38% & 52%, respectively (Fig 1A/1B). On MVA, factors associated with inferior PFS were: advancing age (continuous HR 1.05, P<.001); anemia (HR 1.14, P=.0035); high CIRS-G (HR 1.038, P=0.017) and geriatric syndrome (HR 1.537, P=.0098) (Fig 1C); and for inferior OS: advancing age (continuous HR 1.04, P=.01); low albumin (HR 2.203, P<.001); high CIRS-G (HR 1.053, P=.011); and geriatric syndrome (HR 1.851, P=.005) (Fig 1D). Among all pts, increasing HD MTX dosing in 500 mg/m2 increments was associated with improved PFS (HR 0.958, P=.0002) & OS (HR 0.954, P=.001); and pts treated with MTR had improved PFS & OS vs MPV or MR (Fig 1E /1F). The favorable effect of MTR vs MR persisted when controlling for age, CIRS-G & geriatric syndrome. Additionally, use of Rtx was associated with improved outcomes (PFS HR 0.592, P<.0001; OS HR 0.528, P<0.0001). Finally, pts achieving CR had significantly improved survival (Fig 1G/1H).

Conclusions: Older pts with PCNSL have suboptimal outcomes, with 2/3 progressing in the first several years. GA is an important prognostic tool, and could be used to stratify pts in future investigations. In addition, use of Rtx, increasing MTX dose, and the MTR regimen were associated with improved outcomes.

Disclosures: Reddy: Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy; Celgene: Consultancy; BMS: Consultancy, Research Funding. Bachanova: Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; FATE: Research Funding; BMS: Research Funding; Incyte: Research Funding. Bond: Seattle Genetics: Honoraria. Goldlust: COTA: Other; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau; Boston Biomedical: Consultancy; Cortice Bio: Consultancy, Other: travel; WEX: Consultancy, Other: travel. Spurgeon: Beigene: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Acerta: Research Funding; AstraZeneca: Research Funding; Genmab: Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding. Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali: BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Naik: Celgene: Other: advisory board; Sanofi: Other: advisory board. Martin: Morphosys: Consultancy; Regeneron: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Kite: Consultancy; Teneobio: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Incyte: Consultancy. Smith: Acerta: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy, Research Funding; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; Pharmacyclics: Research Funding; FortySeven: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Rubenstein: Kymera: Research Funding. Kahl: AbbVie: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; Genentech: Consultancy; Pharmacyclics LLC: Consultancy; Roche Laboratories Inc: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Evens: Merck: Consultancy, Honoraria, Research Funding; Research To Practice: Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria.

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