10 results on '"Elyse I. Harris"'
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2. Consensus Cachexia Criteria Are Independently Linked to Progression Free and Overall Survival in Multi-Site Analysis of Patients with Aggressive B-Cell Lymphomas Treated with CAR T-Cell Therapy
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Ishan Roy, Narendranath Epperla, Geoffrey Shouse, Jason T. Romancik, Tamara K. Moyo, Vaishalee P. Kenkre, Thomas A. Ollila, Lindsey A. Fitzgerald, Brian T. Hess, Andrew M. Evens, Joanna Zurko, Sayan Mullick Chowdhury, Kaitlin Annunzio, Robert Ferdman, Rahul S. Bhansali, Elyse I. Harris, McKenzie Sorrell, Jieqi Liu, Imran A. Nizamuddin, Jonathan Moreira, Shuo Ma, Jane N. Winter, Barbara Pro, Deborah M. Stephens, Alexey V Danilov, Nirav N. Shah, Jonathon B. Cohen, Stefan K. Barta, Pallawi Torka, Leo I. Gordon, and Reem Karmali
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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3. Impact of Race and Social Determinants of Health on Outcomes in Patients with Aggressive B-Cell Lymphomas Treated with Chimeric Antigen Receptor T-Cell (CART) Therapy
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Reem Karmali, Narendranath Epperla, Geoffrey Shouse, Jason T. Romancik, Tamara K. Moyo, Vaishalee P. Kenkre, Thomas A. Ollila, Lindsey A. Fitzgerald, Brian T. Hess, Andrew M. Evens, Ishan Roy, Joanna Zurko, Sayan Mullick Chowdhury, Kaitlin Annunzio, Robert Ferdman, Rahul Bhansali, Elyse I. Harris, McKenzie Sorrell, Jieqi Liu, Imran A. Nizamuddin, Shuo Ma, Jonathan Moreira, Jane N. Winter, Barbara Pro, Deborah M. Stephens, Alexey V Danilov, Nirav N. Shah, Jonathon B. Cohen, Stefan K. Barta, Pallawi Torka, and Leo I. Gordon
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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4. Double Hit/Double Expressor Lymphomas: A Multicenter Analysis of Survival Outcomes with CD19-Directed CAR T-Cell Therapy
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Joanna Zurko, Geoffrey Shouse, Pallawi Torka, Tamara K. Moyo, Jason T. Romancik, Imran A. Nizamuddin, Kaitlin Annunzio, Jieqi Liu, Stefan K. Barta, Robert Ferdman, Rahul Bhansali, Jonathon B. Cohen, Sayan Mullick Chowdhury, Nirav N. Shah, Elyse I. Harris, Vaishalee P. Kenkre, McKenzie Sorrell, Brian T. Hess, Deborah M. Stephens, Lindsey A. Fitzgerald, Thomas A. Ollila, Ishan Roy, Shuo Ma, Jane N. Winter, Barbara Pro, Jonathan Moreira, Leo I. Gordon, Alexey V Danilov, Andrew M. Evens, Narendranath Epperla, and Reem Karmali
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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5. Checkpoint Inhibitors Based Salvage Regimens Lead to Higher Survival in Relapsed Refractory Classic Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant
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Sanjal H Desai, Michael A Spinner, Kevin David, Veronika Bachanova, Gaurav Goyal, Brad S. Kahl, Kathleen Dorritie, Jacques Azzi, Vaishalee P Kenkre, Sally Arai, Cheryl Chang, Brendon Fusco, Nuttavut Sumransub, Haris Hactic, Raya Saba, Uroosa Ibrahim, Elyse I Harris, Matthew J Maurer, Harsh Shah, Nina Wagner-Johnston, Deepa Jagadeesh, Victor Orellana-Noia, Catherine Diefenbach, Siddharth Iyengar, KC Rappazzo, Rahul Mishra, Yun Choi, Grzegorz S Nowakowski, Ranjana Advani, and Ivana N Micallef
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
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6. Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL
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Joanna C Zurko, Imran Nizamuddin, Narendranath Epperla, Kevin A David, Jonathon B. Cohen, Tamara Moyo, Thomas A Ollila, Brian T. Hess, Ishan Roy, Robert Ferdman, Jieqi Liu, Sayan Mullick Chowdhury, Jason T. Romancik, Rahul S Bhansali, Elyse I. Harris, Mckenzie Sorrell, Rebecca Masel, Adam S Kittai, Nathan Denlinger, Audrey M Sigmund, Lindsey A. Fitzgerald, Carlos Galvez, Shuo Ma, Jane N Winter, Barbara Pro, Leo I Gordon, Alexey V Danilov, Deborah M. Stephens, Nirav N Shah, Vaishalee P Kenkre, Stefan K Barta, Pallawi Torka, Geoffrey Shouse, and Reem Karmali
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Hematology - Abstract
Most patients receiving CAR T-cell therapy (CAR-T) for aggressive B-cell lymphoma (B-NHL) will not experience a durable remission. There are several novel agents approved for the treatment relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T (peri-CAR-T). We conducted a multicenter retrospective analysis for the purpose of describing peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n=514) from thirteen centers treated with CAR-T for aggressive B-NHL between 2015-2021 were included. Clinical characteristics, CAR-T outcomes and treatment regimens administered pre- and post-CAR-T were collected. Survival curves were constructed using Kaplan Meier method. Multivariate Cox regression was used to determine the impact of variables on survival outcomes. For all patients receiving CAR-T, a greater number lines of therapy prior to CAR-T apheresis and receipt of bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). From time of CAR-T infusion, median PFS and OS were 7.6 and 25.6 months (n=514). From time of progression post-CAR-T (n=254), median OS was 5.5 months. The median PFS of treatments given in the first-line post-CAR-T failure (n=167) was just 2.8 months. Patients with refractory disease at day 30 had inferior OS and were less likely to receive subsequent treatment(s) compared to other patients with CAR-T failure. AlloHCT for select patients at any time following CAR-T failure (n=16) led to durable responses in over half at one-year. These data provide a benchmark for future clinical trials in patients with progression post-CAR-T, an unmet clinical need.
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- 2022
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7. Doppler ultrasound screening in patients with newly diagnosed heparin-induced thrombocytopenia
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Eliot C. Williams, Matthew J. Brunner, Luke D. Zurbriggen, and Elyse I. Harris
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medicine.medical_specialty ,Heparin ,business.industry ,Ultrasonography, Doppler ,Hematology ,Newly diagnosed ,medicine.disease ,Thrombocytopenia ,Heparin-induced thrombocytopenia ,Research Letter ,medicine ,Humans ,In patient ,Radiology ,Doppler ultrasound ,business ,Ultrasonography - Published
- 2021
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8. Practice Patterns Pre-CART for Aggressive B-Cell Lymphomas: Patient Selection and Real World Salvage and Bridging Practices
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Narendranath Epperla, Leo I. Gordon, Alexey V. Danilov, Lindsey Fitzgerald, Brian T. Hess, Imran Nizamuddin, Pallawi Torka, Sayan Mullick Chowdhury, Robert Ferdman, Deborah M. Stephens, Rahul S. Bhansali, Geoffrey Shouse, Jonathon B. Cohen, Shuo Ma, Reem Karmali, Kevin A. David, Barbara Pro, Carlos Galvez, Jane N. Winter, Rebecca Masel, Nirav N. Shah, Kaitlyn O'Shea, Stefan K. Barta, Jason T. Romancik, Mckenzie Sorrell, Vaishalee P. Kenkre, Joanna C. Zurko, Elyse I. Harris, Jieqi Liu, and Thomas A Ollila
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Oncology ,Cart ,medicine.medical_specialty ,Bridging (networking) ,Practice patterns ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,medicine.anatomical_structure ,Internal medicine ,medicine ,business ,Selection (genetic algorithm) ,B cell - Abstract
Introduction The treatment of aggressive B-cell NHL has evolved rapidly over the last 5 years, owing to the FDA approval of 3 CD19 CAR T-cell constructs (CARTs) along with other novel targeted therapies. Real world practice data suggest that CARTs have been successfully administered in populations typically excluded from clinical trials. However, data on how to best utilize novel targeted agents as a pathway to CARTs and feasibility of CARTs in rare histologies remains limited. This retrospective multicenter study describes patient (pt) selection and practice patterns in pts treated with CD19 CARTs and provides insight on feasibility of CARTs in special populations. Methods Adult pts with R/R aggressive B-cell NHL treated with CD19 CARTs between 2015- 2020 across 12 US academic centers were identified. Data on demographic and clinical characteristics, disease and toxicity outcomes were collected. Univariate analyses (UVA) were performed to determine impact of demographic/clinical variables on survival. Survival curves were calculated using Kaplan-Meier method. Subgroup analysis was performed for pts with secondary central nervous system lymphoma (sCNSL). Results Clinical and demographic features were recorded from 400 pts (Table 1). Median age was 59 years (range 18-84). Of 271 pts with immunohistochemistry data, 79 (29%) had double-expressor lymphoma. Of 178 pts with FISH data captured, 62 (35%) had double/triple-hit lymphoma. Most common histological subtypes included 271 (68%) pts with de novo DLBCL, 81 (20%) with transformed FL, 13 (3%) with Richter's syndrome, and 8 (2%) with PMBCL. Rare histologies included 7 (2%) with transformed MZL, 5 (1%) with PTLD and 2 (0.5%) with grey zone lymphoma. 24 (6%) pts had sCNSL at time of CART apheresis. Two (0.5%) pts were HIV-positive. Median number of lines of therapy prior to CART was 2 (range 1-8); 182 (46%) pts received ≥ 3 lines. 114 (28%) pts previously had an autologous stem cell transplant. Targeted therapies used as salvage regimens at any point prior to CART are listed in Table 2: commonly used salvage targeted therapies included lenalidomide based therapy (imids, n=37, 9%), BTK inhibitors (BTKis, n=30, 8%), checkpoint inhibitors (CBIs, n=17, 4%) and polatuzumab-containing regimens (n=10, 3%). 2 (1%) pts received loncastuximab, and no pts received tafasitamab. Six (1.5%) pts proceeded to CART despite complete response to most recent pre-CART therapy. 191 (48%) pts received bridging between apheresis and CART infusion, choice of bridging noted in Table 2: the majority received chemotherapy (n=103, 54%); 28 (15%) received radiation (XRT); 25 (13%), 24 (13%) and 18 (9%) pts received imids, polatuzumab-containing regimens, or BTKis, respectively. With median follow-up of 22.4 months (mo) for the overall group, median (m) PFS was 11 mo (n=363); mOS, was 27 mo (n=397; Fig 1). Pts with sCNSL had a mPFS and mOS of 2 and 4 mo, respectively (Fig 1). On UVA, factors predicting poorer PFS and OS in the overall group included ≥3 pre-CART lines (p For outcomes according to bridging regimens: mPFS after CART for most commonly used systemic bridging therapies was 86 days (d) for platinum-based chemotherapy, 77 d for imids, 90 d for BTKis, 98 d for polatuzumab-bendamustine/rituximab, and 274 d for XRT. Median PFS for XRT bridging (274 d) was statistically better when compared to mPFS for listed systemic therapies combined (p Conclusion Survival outcomes with CARTs in our data set are consistent with those reported in clinical trial settings. CARTs are utilized in real world practice in rare subsets of aggressive R/R B-cell NHL not routinely included in clinical trials. Despite early data suggesting pts with sCNSL benefit from CART, our data suggest outcomes with CART are dismal in this group. Targeted therapies including imids, polatuzumab, BTKis and CBIs are feasible choices for salvage and/or bridging as a pathway to CARTs. Bridging with XRT resulted in improved mPFS post CART as compared to bridging with systemic therapies and suggests differences in pt selection for each with systemic therapies likely favored in those with more widespread disease burden. Minimal use of CD19-targeted agents pre-CART is attributed to later approval of these agents and concern for potential loss of CD19 antigen leading to CART resistance. Figure 1 Figure 1. Disclosures Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Shouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Stephens: Beigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Arqule: Research Funding; Mingsight: Research Funding; JUNO: Research Funding; Celgene: Consultancy; CSL Behring: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ma: Loxo: Research Funding; AstraZeneca: Honoraria, Research Funding, Speakers Bureau; Juno: Research Funding; Beigene: Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding; Janssen: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding, Speakers Bureau. Winter: BMS: Other: Husband: Data and Safety Monitoring Board; Actinium Pharma: Consultancy; Janssen: Other: Husband: Consultancy; Gilead: Other: Husband: Consultancy; Agios: Other: Husband: Consultancy; Epizyme: Other: Husband: Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Danilov: Astra Zeneca: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Gilead Sciences: Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Rigel Pharm: Honoraria; Bayer Oncology: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding. Shah: Umoja: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Incyte: Consultancy. Barta: Seagen: Honoraria; Daiichi Sankyo: Honoraria; Acrotech: Honoraria; Kyowa Kirin: Honoraria. Epperla: Genzyme: Honoraria; Karyopharm: Other: Ad Board; Beigene: Speakers Bureau; Verastem: Speakers Bureau. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Karmali: Epizyme: Consultancy; BeiGene: Consultancy, Speakers Bureau; EUSA: Consultancy; Roche: Consultancy; AstraZeneca: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Takeda: Research Funding; BMS/Celgene/Juno: Consultancy, Research Funding; Janssen/Pharmacyclics: Consultancy; Genentech: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau.
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- 2021
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9. Novel Salvage Regimens Lead to Better Response and Survival in Relapsed Refractory Classic Hodgkin Lymphoma after Autologous Stem Cell Transplant
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Saba Raya, Catherine Diefenbach, Nuttavut Sumransub, Jacques Azzi, Sanjal Desai, Grzegorz S. Nowakowski, Sally Arai, Michael A. Spinner, Gaurav Goyal, Vaishalee P. Kenkre, Haris Hactic, Victor M. Orellana-Noia, Ranjana H. Advani, Ivana N. Micallef, Matthew J. Maurer, Elyse I. Harris, Veronika Bachanova, Uroosa Ibrahim, Kevin A. David, Cheryl H. Chang, KC Rappazzo, Brendon Fusco, and Kathleen A. Dorritie
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Internal medicine ,Relapsed refractory ,medicine ,Hodgkin lymphoma ,Stem cell ,Lead (electronics) ,business - Abstract
Introduction: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) after autologous stem cell transplant (ASCT); yet studies comparing novel ST with conventional salvage chemotherapy are lacking. In a single center cohort, we demonstrated that bendamustine/brentuximab (BBV) had higher overall response rates (ORR) and complete response (CR) rates in ASCT-eligible R/R cHL (Desai et al JCO, 2021). Herein we report comparative outcomes of novel and conventional ST in R/R cHL who undergo ASCT, in a large multicenter retrospective cohort. Methods: Consecutive R/R cHL pts who underwent ASCT at 12 institutions across United States were included. Demographics and clinical variables at relapse including age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year) were recorded by electronic health records review. Study objectives were ORR, CR to first ST, post-ASCT PFS and OS by final ST. Time to event endpoints were defined from date of ASCT. Results: From 12 participating institutions, 853 pts of R/R cHL who underwent ASCT were eligible for this study. Median age was 33 (14-72) years, 457 (54%) were male, 446 (52%) had BD, 257 (30%) had advanced stage, 271 (32%) had END, 369 (43%) had B symptoms, 142 (17%) had PRD and 307 (36%) had ER. All 853 received at least 1 ST, 245 received 2 ST, 71 received 3 ST and 26 received 4 ST. Seven groups of ST were identified: 1. Conventional platinum-based chemotherapy (PBC) group including ICE, DHAP and ESHAP 2. BBV 3. Brentuximab Vedotin and nivolumab (BV/Nivo) 4. BV alone (BV) 5. gemcitabine-based chemotherapy (Gem) 6. checkpoint inhibitors (CPI) and 7. other miscellaneous agents (Misc). 1st ST was as follows: 553 had PBC; 69 had BBV; 48 had BV/Nivo; 65 had BV; 49 had Gem; 4 had CPI and 63 had Misc. There was no significant difference in the baseline characteristics by type of 1 st ST (data not shown). BBV had significantly higher ORR (92% vs 79%, p Final ST prior to ASCT was PBC in 451, BBV in 76, BV/Nivo in 48, BV in 87, CPI in 24, Gem in 90 and Misc in 64. Table 1 lists K-M estimates of 2-year survival probabilities for different Final ST groups. Median follow up was 3 (range 0.1-13) years. BV/Nivo group had significantly higher proportion of patients with PRD and BD than PBC, no other differences in baseline characteristics were identified amongst ST groups (data not shown). BV/Nivo (HR: 0.1 (CI 95:0.02-0.4), p 536 pts underwent ASCT in CR, 273 underwent ASCT in partial response (PR) and 31 underwent ASCT with progressive disease (PD). Pre-ASCT PR (HR 1.6 (CI 95:1.3-2.6), p In pts with pre-ASCT CR, all 36 who had pre-ASCT CR after BV/Nivo were alive and relapse free for follow up of 0.1-5 yrs. BV/Nivo was associated with significantly higher PFS (HR 0.1 (CI 95: 0.01-0.7), p Conclusions: BV/Nivo has a higher CR rate and better post-ASCT PFS compared to conventional chemotherapy and can lead to durable remissions in pts with pre-ASCT CR. BBV had a higher response rate and similar post-ASCT survival to conventional chemotherapy. BV had lower response rates compared to chemotherapy. Novel ST such as BV/Nivo and BBV may be preferable to conventional chemotherapy in R/R cHL. Figure 1 Figure 1. Disclosures Spinner: Notable Labs: Honoraria. Bachanova: FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dorritie: SITC presentation: Honoraria; Genmab: Research Funding; University of Pittsburgh/UPMC Hillman Cancer Center: Current Employment; Janssen: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Juno/BMS: Research Funding; Kite, a Gilead Company: Research Funding; OncLive/Institutional Perspectives on Cancer presentation: Honoraria. Arai: Magenta Therapeutics: Research Funding. Maurer: Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Diefenbach: Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; IMab: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment; AbbVie: Research Funding; IGM Biosciences: Research Funding; Incyte: Research Funding; Trillium: Research Funding; Gilead: Current equity holder in publicly-traded company; MEI: Consultancy, Research Funding. Nowakowski: Kyte Pharma: Consultancy; Ryvu Therapeutics: Consultancy; Selvita: Consultancy; Curis: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MorphoSys: Consultancy; Bantham Pharmaceutical: Consultancy; Daiichi Sankyo: Consultancy; Zai Labolatory: Consultancy; Incyte: Consultancy; Kymera Therapeutics: Consultancy; TG Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Nanostrings: Research Funding. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees.
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- 2021
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10. Outcomes and Treatment Patterns in Patients with Aggressive B-Cell Lymphoma after Failure of Anti-CD19 CAR T-Cell Therapy
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Rahul S. Bhansali, Brian T. Hess, Carlos Galvez, Imran Nizamuddin, Pallawi Torka, Deborah M. Stephens, Geoffrey Shouse, Sayan Mullick Chowdhury, Nirav N. Shah, Thomas A Ollila, Jieqi Liu, Leo I. Gordon, Reem Karmali, Alexey V. Danilov, Elyse I. Harris, Rebecca Masel, Kevin A. David, Stefan K. Barta, Lindsey Fitzgerald, Narendranath Epperla, Barbara Pro, Jason T. Romancik, Jonathon B. Cohen, Robert Ferdman, Jane N. Winter, Mckenzie Sorrell, Vaishalee P. Kenkre, Joanna C. Zurko, Kaitlyn O'Shea, and Shuo Ma
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business.industry ,Anti cd19 ,Immunology ,medicine ,Cancer research ,CAR T-cell therapy ,In patient ,Cell Biology ,Hematology ,B-cell lymphoma ,medicine.disease ,business ,Biochemistry - Abstract
Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospective analysis with a primary objective to assess treatment patterns and outcomes in pts with R/R aggressive B-cell lymphoma who develop PD after anti-CD19 CARTs. Methods: Pts with aggressive B-cell lymphoma treated with anti-CD19 CART between 2015 and 2020 across 12 US academic medical centers were included. Demographic and clinical characteristics were collected along with CART toxicities and response. Regimens administered as salvage post CART were assessed. Univariate analyses (UVA) were performed to determine impact of demographic and clinical variables on survival outcomes. All p-values were two-tailed. Survival curves were calculated using the Kaplan-Meier method. Results: A total of 400 pts received anti-CD19 CARTs and were included for analysis. For the entire cohort: median PFS and OS from time of CART infusion were 11 months [mo] and 27 mo respectively. On log-rank testing, pts who received ≥3 lines of pre-CART therapy and those with refractory disease pre-CART had significantly worse PFS (p=0.004 & 0.001) and OS (both p With median follow-up 22.4 mo, 190 pts (48%) had PD after CART; demographic and clinical variables of pts with and without PD are detailed in Table 1. Biopsy to confirm PD and assess CD19 status was done in 69 pts (36%) with CD19 negative relapse seen in 11 (16%). Of pts with PD, median PFS and OS from time of PD was 83 days (in pts who received salvage) and 174 days (for all PD pts) respectively. Pts with PD were more likely to have elevated LDH (p=0.001) and extranodal disease (p=0.003) at apheresis. For pts with PD after CART: 125 (65.5%) received further therapies. Pts were more likely to receive salvage therapies if their best response to CART was CR (p=0.026) or PR (p=0.015). Response rates of select first- and second-line therapies and PFS of first line therapies received after CART failure are detailed in figure 1. ORR and CRs were highest for polatuzumab, bendamustine, & rituximab (pola-BR; 73% & 40%), followed by BTK inhibitors (BTKi; 50% & 38%), and bispecific antibodies (bsAb) (50% & 25%). Five of 7 pts who received a BTKi had non-germinal center (GC) cell of origin (COO; 1 unknown COO). On log-rank testing, pts with elevated LDH (p=0.003) at time of apheresis and those with intermediate/high IPI (p=0.013) had inferior PFS with first salvage regimens. Median PFS was highest for pola-BR (4.5 mo, n=14), followed by bsAb (2.5 mo, n=8), lenalidomide +/- anti-CD20 antibody (1.8 mo, n=13), checkpoint inhibitors (CPI; 1.6 mo, n=10), BTKi (1.2 mo, n=8), radiation alone (1.2 mo; n=17), chemotherapy (1.1 mo, n=12), and tafasitamab + lenalidomide (0.9 mo, n=5). Median PFS for all treated pts was 1.8 mo. OS from start of first salvage regimen was highest for CPI (OS 12.4 mo, n=10), followed by pola-BR (8.9 mo, n=14), BTKi (8.8 mo, n=8), lenalidomide +/- anti-CD20 (8.7 mo, n=13), radiation alone (7.1 mo, n =17), bsAb (5.9 mo, n=8), chemotherapy (5.4 mo, n=12), and tafasitamab + lenalidomide (1.2 mo, n=5). 12 pts (6.3%) later received an allogeneic hematopoietic cell transplant (alloHCT). In alloHCT pts at last follow-up, 10 were evaluable for response: 7 had CR and 5 remain in CR. Clinical characteristics of pts who received alloHCT are detailed in table 2. Notably, median age was 59 years (41-68), 1 (8.3%) had a prior alloHCT, and 6 (50%) had prior autologous HCT. The majority had CR or PR as best response to CART (CR n=6, 50%; PR n=3, 25%), and only 1 pt (8.3%) with PD as best response to CART was salvaged with alloHCT. Conclusions: This is the largest reported analysis to date of pts with aggressive B-cell lymphoma who develop PD post-CART. The highest ORRs were with pola-BR, bsAb, and BTKi as first line of salvage. High response rates with BTKi may be attributed to non-GC COO in the majority of treated pts and perhaps a beneficial immunomodulatory effect on previously administered CARTs. AlloHCT remains a potential curative therapy for select pts with over half with durable remission; however, few ultimately received alloHCT. Despite increased use of novel therapies, survival in pts who progress after CART is still dismal warranting more effective therapies. Figure 1 Figure 1. Disclosures Epperla: Genzyme: Honoraria; Karyopharm: Other: Ad Board; Beigene: Speakers Bureau; Verastem: Speakers Bureau. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Ma: Abbvie: Honoraria, Research Funding; Beigene: Research Funding, Speakers Bureau; Loxo: Research Funding; Juno: Research Funding; AstraZeneca: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding, Speakers Bureau. Winter: Gilead: Other: Husband: Consultancy; Janssen: Other: Husband: Consultancy; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Epizyme: Other: Husband: Data and Safety Monitoring Board; Agios: Other: Husband: Consultancy; Actinium Pharma: Consultancy; BMS: Other: Husband: Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Danilov: Bayer Oncology: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Rigel Pharm: Honoraria; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; SecuraBio: Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Gilead Sciences: Research Funding. Stephens: Adaptive: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; JUNO: Research Funding; Mingsight: Research Funding; CSL Behring: Consultancy; Novartis: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Arqule: Research Funding; Celgene: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shah: Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Umoja: Consultancy; Incyte: Consultancy; Kite: Consultancy; Legend: Consultancy; Epizyme: Consultancy; Lily: Consultancy, Honoraria, Research Funding. Shouse: Beigene Pharmaceuticals: Honoraria; Kite Pharmaceuticals: Speakers Bureau. Barta: Acrotech: Honoraria; Daiichi Sankyo: Honoraria; Seagen: Honoraria; Kyowa Kirin: Honoraria. Karmali: Karyopharm: Consultancy; EUSA: Consultancy; Roche: Consultancy; Janssen/Pharmacyclics: Consultancy; Genentech: Consultancy; Morphosys: Consultancy, Speakers Bureau; Epizyme: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Consultancy, Research Funding; AstraZeneca: Speakers Bureau; Takeda: Research Funding; BeiGene: Consultancy, Speakers Bureau.
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