-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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465 Development of a Novel Prognostic Score for Relapsed/Refractory Mature T-Cell and NK-Cell Lymphomas (PIRT): Results from a Global Peripheral T-Cell Lymphoma (PETAL) Consortium

Program: Oral and Poster Abstracts
Type: Oral
Session: 625. T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: When Old Meets New in T Cell Lymphomas
Hematology Disease Topics & Pathways:
Research, Combination therapy, Antibody Therapy, Adult, Epidemiology, Lymphomas, Clinical Research, Health outcomes research, Chemotherapy, Health disparities research, T Cell lymphoma, Checkpoint Inhibitor, Diseases, Therapy sequence, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Biological therapies, Immunotherapy, Lymphoid Malignancies, Non-Biological therapies, Monoclonal Antibody Therapy, Study Population, Human, Transplantation (Allogeneic and Autologous)
Sunday, December 8, 2024: 10:00 AM

Min Jung Koh, MS1*, Jessy Xinyi Han, BS2*, Leora Boussi, MD3, Mark N Sorial, PharmD, RPh4*, Sean M McCabe, BS5*, Luke Peng, BS6*, Shambhavi Singh, MD, PhD7, Ijeoma Julie Eche-Ugwu, PhD8,9*, Judith Gabler, MD10*, Maria J. J. Fernandez Turizo, MD11, Caroline MacVicar, BA5*, Aditya Garg7*, Alexander Disciullo, MD12*, Kusha Chopra, BA5*, Alexandra W Lenart, BA5*, Emmanuel Nwodo7*, Jeffrey A. Barnes, MD, PhD13,14, Min Ji Koh, BA10*, Eliana Miranda, MEd, PhD15*, Carlos Chiattone, MD, PhD16, Robert Stuver, MD17, Steven Horwitz, MD17, Mwanasha H. Merrill, MD18, Eric D. Jacobsen, MD19, Jin Seok Kim, MD, PhD20*, Yu Ri Kim, MD21, Jae Yong Cho, MD, PhD22*, Thomas Eipe, PharmD23*, Tanuja Shet, MBBS, MD, DPB, DNB, DTM24*, Epari Sridhar, MD24*, Alok Shetty, MD, DM25*, Saswata Saha, DM26*, Hasmukh Jain, MD, DM27*, Manju Sengar, MD, DM27, Carrie Van Der Weyden, MBBS (Hons), FRACP, FRCPA28*, H. Miles Prince, MD, MBBS29, Ramzi Hamouche, MD30, Tinatin Muradashvili, MD31*, Francine M. Foss, MD32, Marianna Gentilini, MD33*, Beatrice Casadei, MD34*, Pier Luigi Zinzani, MD35,36, Takeshi Okatani, MD37*, Noriaki Yoshida, MD, PhD38, Sang Eun Yoon, MD39*, Won Seog Kim, MD40*, Girisha Panchoo, MBBS41*, Zainab Mohamed, MBChB, MMed42*, Estelle Verburgh, MBChB, M Med Int, FCPSA, PhD42, Jackielyn Cuenca Alturas, BA43*, Mubarak Al Mansour, MD44*, Josie G Ford, BSc45, Martina Manni, PhD46*, Monica Civallero, PhD47*, Tetiana Skrypets, MD48*, Massimo Federico, MD49, Maria Elena Cabrera, MD50*, Amy Ku, MD, PhD51*, Govind Bhagat, MD52, Helen Ma, MD53, Ahmed Sawas, MD54, Khyati Kariya, PhD10*, Makoto Iwasaki, MD, PhD10, Forum Bhanushali55*, Owen A. O'Connor, MD, PhD56, Enrica Marchi, MD, PhD57, Changyu Shen, PhD58*, Devavrat Shah, PhD2* and Salvia Jain, MD59

1Georgetown University School of Medicine, Arlington, VA
2Massachusetts Institute of Technology, Cambridge, MA
3Department of Medicine; Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
4Department of Pharmacy, Massachusetts General Hospital Cancer Center, Boston, MA
5Department of Medicine, Massachusetts General Hospital, Boston, MA
6College of Science, Northeastern University, Boston, MA
7Massachusetts General Hospital, Boston, MA
8Phyllis F. Cantor Center for Research in Nursing and Patient Care Services, Dana-Farber Cancer Institute, Boston, MA
9Beth Israel Deaconess Medical Center, Boston, MA
10Massachusetts General Hospital Cancer Center, Boston, MA
11Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA
12Cancer Center, Massachusetts General Hospital, Boston, MA
13Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA
14Harvard Medical School, Boston, MA
15University of Campinas (UNICAMP), Hematology and Hemotherapy Center (Hemocentro), Campinas, Brazil
16Santa Casa Medical School of Sao Paulo, Sao Paulo, Brazil
17Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
18Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
19Dana Farber Cancer Institute, Boston, MA
20Severance Hospital, Yonsei University Health System, Seoul, Korea, Republic of (South)
21Division of Hematology, Department of Internal Medicine, Hematology, Gangnam Severance Hospital, Seoul, South Korea
22Department of Medicine, Gangnam Severance Hospital, Yonsei University School of Medicine, Seoul, Korea, Republic of (South)
23Department of Clinical Pharmacology, Tata Memorial Centre, Mumbai, India
24Department of Pathology, Tata Memorial Centre, Mumbai, India
25Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
26Department of Medical Oncology, Tata Memorial Centre, Navi Mumbai, Maharashtra, IND
27Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
28Department of Hematology, Peter MacCallum Cancer Center, Melbourne, VIC, AUS
29Peter MacCallum Cancer Inst., East Melbourne, VIC, AUS
30Department of Hematology, Yale Cancer Center, New Haven, CT
31Department of Hematology, Yale University, Cliffside Park, NJ
32Yale University School of Medicine, Hamden, CT
33Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
34IRCCS Azienda Ospedaliero-Universitaria di Bologna  Istituto di Ematologia “Seràgnoli”, Bologna, Italy
35University of Bologna, Istituto Di Ematologia, Bologna, Italy
36Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
37Hiroshima Red Cross & A-Bomb Survivors Hospital, Hiroshima City, JPN
38Radiation Effects Research Foundation, Hiroshima-Shi, JPN
39Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea, Republic of (South)
40Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
41University of Cape Town and Groote Schuur Hospital, Cape town, South Africa
42University of Cape Town, Cape Town, South Africa
43Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
44Department of Medicine, King Abdulaziz Medical City, Jeddah, SAU
45Department of Medicine, Massachusetts General Hospital, Farmington, CT
46Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, ITA
47CHIMOMO Department, University of Modena and Reggio Emilia, Modena, ITA
48Hematology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Modena, AL, Italy
49Oncologia Medica, University of Modena and Reggio Emilia, Modena, Italy
50Hematology Department, Hospital del Salvador, Santiago, Chile
51Department of Pathology and Cell BIology, Columbia University Irving Medical Center, New York, NY
52Department of Pathology & Cell Biology, Columbia University, New York, NY
53VA Long Beach Health System, University of California, Irvine, Long Beach, CA
54Lymphoma Program, Division of Hematology & Oncology, Columbia University Irving Medical Center, New York
55Brigham and Women's Hospital, Boston, MA
56Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA
57Program for T-Cell Lymphoma Research, University of Virginia, Charlottesville, VA
58Biogen, Cambridge, MA
59Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA

The variability in global access to medications and treatment practices make it challenging to evaluate the benefits of contemporary therapies for patients with relapsed and refractory (R/R) mature T-cell and NK-cell lymphomas (MTCL and MNKCL). While numerous prognostic factors and models have been suggested to categorize the risk levels of patients with MTCL and MNKCL, they have primarily been developed for newly diagnosed patients. On the other hand, for the common subtypes of R/R MTCL and MNKCL patients, the identification of risk factors and subgroups that lead to variability in treatment outcomes and overall survival (OS) is still not well established. Thus, a new prognostic model is needed to further refine subgroups with varied outcomes in R/R patients.

We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL diagnosed between Jan 2010 and Sept 2021 who received either “novel” single agent (SA) or cytotoxic chemotherapy (CC) for second line treatment from 13 institutions representing 10 countries. We first split our global cohort of 763 patients with second line treatment details into a training set (80%) and a testing set (20%). Among the 21 available demographics, histological, laboratory, radiologic non-treatment characteristics, we identified 11 variables on univariable analysis to be associated with inferior OS from the start of second-line treatment. Based on the step-by-step selection in multivariable Cox regression (MVC) and clinical considerations, our final model that combined 6 of the 11 features was chosen based on the highest Concordance index (C-index) among the models that incorporated covariates retaining an independent prognostic value (p £ 0.05 in the testing set. The six variables in the final model included age being greater than 60, primary refractory disease in contrast to relapsed, histological subtypes other than AITL, extranodal sites greater than 1, Ki-67 proliferation index (%) being 40 or greater, and absolute lymphocyte count around diagnosis being lower than Lower Limit of Normal (LLN).

We then created a new prognostic index for R/R TCL (PIRT) score to estimate OS from start of second-line treatment, which ranged from 0 to 6. We assigned a score of 1 to each unfavorable feature since the relative risks associated with each of these 6 factors are similar. When patients were initially categorized into 6 subgroups, we observed a clear declining trend of OS with an increasing score. Patients were stratified into 3 final risk group: low- (0-1 risk factor), intermediate- (2-3 risk factors), or high- (3-4 risk factors) groups, which showed notable similarity between their predicted and actual survival. In the training set, the median 3-yr OS for the low-risk group was 75.2% (95% CI: 29.7 - 85.2) vs intermediate-risk group (50.6%, 95% CI: 37.7 - 58.9) vs the high-risk group (16%, 95% CI: 7.7 - 26.9). The three risk groups were also segregated in the testing set with disparate 3-yr OS with low-risk (57.1%, 95% CI: 17.1 - 83.7) vs intermediate-risk (23.3%, 95% CI: 8.7 - 41.9) vs the high-risk (7.0%, 95% CI: 0.4 - 26.9). An analysis of 1000 bootstrapped testing sets showed that our PIRT score achieved a higher prediction probability with an average C-index of 0.7 (95% CI: 0.63 - 0.76) compared to IPI (0.56, 95% CI: 0.5 - 0.63) and PIT (0.59, 95% CI: 0.52 - 0.65). The paired t-tests between IPI vs. PIRT and PIT vs. PIRT scores confirmed the statistical significance of this performance difference. We also validated our prognostic model’s survival prediction power in an independent multicenter study cohort and developed a web-based calculator for healthcare professionals to use: Website for PIRT Score Calculator

In summary, we developed a new prognostic scoring system for patients with R/R MTCL and MNKCL that was validated in training, testing and independent datasets that has enabled their segregation and has the potential to facilitate clinical decision.

Disclosures: Sorial: Daiichi Sankyo: Research Funding; SecuraBio: Research Funding; The Dedham Group: Consultancy; MJH Life Sciences: Honoraria. Stuver: Pfizer: Research Funding. Horwitz: Auxilius Pharma, Abcuro Inc., Corvus, Daiichi Sankyo, DrenBio, Farallon Capital Management, L.L.C., Kyowa Hakko Kirin, March Bio, Neovii Pharmaceuticals AG, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio, Treeline Bio and Takeda Pharmaceuticals.: Consultancy; Auxilius Pharma, Abcuro Inc., Corvus, CTI BioPharma Corp, Daiichi Sankyo, DrenBio, Kyowa Hakko Kirin, March Bio, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio and Takeda Pharmaceuticals.: Honoraria; ADC Therapeutics, Affimed, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio.: Research Funding. Jacobsen: AstraZeneca: Consultancy; Merck: Consultancy; Pharmacyclics: Consultancy; F. Hoffman-LaRoche: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Ascerta: Consultancy. Kim: Roche: Other: All authors received support for third-party writing assistance, furnished by Akshaya Srinivasan, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.. Van Der Weyden: Kyowa Kirin: Consultancy. Prince: AbbVie: Research Funding; Takeda: Honoraria; Mallinckrodt: Honoraria; Johnson and Johnson: Honoraria; Amgen: Honoraria; Kyowa Kirin: Honoraria; Bristol Myers Squibb: Honoraria; GSK: Honoraria. Zinzani: MSD, EUSAPHARMA, NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO, ADC Therap, Sandoz: Membership on an entity's Board of Directors or advisory committees; CELLTRION, GILEAD, JANSSEN-CILAG, BMS, SERVIER, ASTRAZENECA, TAKEDA, ROCHE, KYOWA KIRIN, Incyte, Beigene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kim: Kyowa-Kirin: Research Funding; Boryong: Research Funding; BeiGene: Research Funding; Sanofi: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Donga: Research Funding. Verburgh: MSD: Research Funding; Takeda: Honoraria; Roche: Honoraria; NIH: Research Funding; CANSA: Research Funding; South African Stem Cell Transplantation Society: Membership on an entity's Board of Directors or advisory committees. Ford: Moderna: Current equity holder in publicly-traded company. Sawas: Flatiron Health Inc.: Current Employment, Current equity holder in publicly-traded company; Seagen: Honoraria; Lilly: Honoraria; Kite: Honoraria; Daiichi: Honoraria. O'Connor: Merck: Research Funding; BMS: Research Funding; Acrotec: Honoraria, Other: Advisor; Myeloid Therapeutics: Current equity holder in publicly-traded company, Honoraria; Dren Bio: Current equity holder in publicly-traded company; Kymera: Current equity holder in publicly-traded company, Honoraria, Other: Scientific advisory board. Marchi: Dren Bio: Consultancy, Research Funding; Seagen: Honoraria; Kymera Therapeutics: Consultancy, Research Funding; U.S. Patent Application Serial No. 18/701,581: Patents & Royalties: U.S. Patent Application Serial No. 18/701,581; Kyowa Kirin: Honoraria; Vittoria Biotherapeutics: Consultancy; Everest Clinical Research: Consultancy; Acrotech: Honoraria; Celgene/BMS: Research Funding; Merck: Research Funding. Shen: Biogen Digital Health: Current Employment. Jain: Kyowakirin: Research Funding; Acrotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; SIRPant Immunotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abcuro Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mersana Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; SecuraBio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Myeloid Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Crispr therapeutics: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: There is no established standard of care in relapsed or refractorymature T and NK cell neoplasms. Agents reported in thisobservational study may have been used off-label as part of clinicalpractice.

*signifies non-member of ASH