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983 Refining Prognostication in Peripheral T Cell Lymphoma (PTCL): A Risk-Adapted Prognostic Model for Patients with Limited-Stage PTCL

Program: Oral and Poster Abstracts
Type: Oral
Session: 625. T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: Are We Ready to Move the Needle in T Cell Lymphomas?
Hematology Disease Topics & Pathways:
Research, Adult, Epidemiology, Lymphomas, Clinical Research, Health outcomes research, T Cell lymphoma, Diseases, Lymphoid Malignancies, Study Population, Human
Monday, December 9, 2024: 5:30 PM

Carolina Romero, MD1*, Macarena Roa, MD2*, Henry Idrobo, MD3*, Denisse Castro, MD4, Brady E Beltran, MD5,6*, Daniel J Enriquez, MD7*, Jule F Vasquez, MD8, Claudia Roche, MD9*, Daniel Artiles, MD10*, Fabiola Valvert, MD, FRCP11, Luis Mario Villela Martinez, MD, MSc12*, Juliana Pereira, MD, PhD13, Ana Carolina Oliver, MD14, Jamila Vaz Tavarez, MD15*, Sergio Augusto B Brasil, MD, PhD16*, Karin Z Cecyn, MD17*, Nelson S Castro, MD18*, Renata Lyrio R Baptista, MD19,20*, Samuel S. Medina, MD21*, Davimar Miranda Maciel Borducchi, PhD22, Marcelo Bellesso, MD23*, Danielle Leão Cordeiro De Farias, MD, MSc, MBA24, Yung Gonzaga, MD25*, Laura Korin, MD26*, Patricio Pereyra, PhD27*, Camila Peña, MD2, Maria Alejandra Torres Viera, MD28*, Kelly Meza, MD29*, Seisha Von Glasenapp, PhD30, Alfredo Quiroz, MD31*, Cesar Samanez-Figari, MD32*, Rosa Oliday Rios Jimenez33*, Sally Paredes, MD4*, Thais Fischer, MD34*, Asaad Trabolsi, MD35, Jonathan H. Schatz, MD36, Swaminathan P Iyer, MD37*, Ranjit Nair, MD38, Eduardo Edelman Saul, MD39, Casey Bermack, MD37, Jorge J. Castillo, MD40, Carmino De Souza, MD, PhD41*, Eliana Miranda, PhD, MEd41*, Bryan Valcarcel, MD, MPH42, Carlos Chiattone, MD, PhD16,43 and Luis Enrique Malpica Castillo, MD44

1Hospital del Salvador, Santiago, Chile
2Hospital Del Salvador, Santiago, Chile
3Universidad del Valle del Cauca, Cali, COL
4Hospital Edgardo Rebagliati Martins, Lima, Peru
5Servicio Oncología Médica, Hospital Edgardo Rebagliati, Lima, Peru
6Instituto de Investigación en Ciencias Biomédicas, Universidad Ricardo Palma, Lima, Peru
7Instituto Nacional De Enfermedades Neoplasicas, Lima, Peru
8Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
9Hospital Armando Milan Castro, Vila Clara, Cuba
10Hospital Arnoldo Milan Castro, Vila Clara, Cuba
11INCAN, Ciudad de Guatemala, Guatemala
12Hospital Fernando Ocaranza, Hermosillo, Mexico
13University of São Paulo, Department of Hematology, Hemotherapy & Cell Therapy, University of São Paulo, São Paulo, São Paulo, Brazil
14Hospital Britanico de Montevideo, Montevideo, Uruguay
15Ophir Loyola Hospital, Belém, Brazil
16Santa Casa Medical School of Sao Paulo, Sao Paulo, Brazil
17Federal University of Sao Paulo, Sao Paulo, Brazil
18Hospital de Cancer de Barretos, Barretos, São Paulo, BRA
19Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, Brazil
20State University of Rio de Janeiro, Rio De Janeiro, Brazil
21University of Campinas, São Paulo, BRA
22Medical School of ABC, Santo Andre, Brazil
23HemoMed, Instituto de Ensino e Pesquisa – IEP, Sao Paulo, Brazil
24Beneficencia Portuguesa Hospital, Sao Paulo, Brazil
25Cancer National Institute, Rio De Janeiro, Brazil
26CABA- Alexander Fleming Institute, Olivos, Argentina
27Hospital Nacional Posadas, Buenos Aires, Argentina
28Clinica Santa Sofia, Caracas, Venezuela (Bolivarian Republic of)
29Baylor College of Medicine, Houston, TX
30Hospital Central Instituto de Previsión Social, Asuncion, Paraguay
31Departamento de Hematología, Hospital Central Instituto de Previsión Social, Asunción, Paraguay
32Oncosalud, AUNA, Lima, Peru
33Hospital Clínico Quirúrgico Hermanos Amejeiras, La Habana, Cuba
34Santa Casa de São Paulo Medical School, São Paulo, Brazil
35University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL
36Department of Hematology, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL
37University of Texas MD Anderson Cancer Center, Houston, TX
38University of Texas MD Anderson Cancer Center, Pearland, TX
39Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
40Dana-Farber Cancer Institute, Bing Center for Waldenström Macroglobulinemia, Boston, MA
41Centro de Hematologia e Hemoterapia (HEMOCENTRO), Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
42George Washington University, Washington, DC
43Hospital Samaritano-Higienopolis, Sao Paulo, Brazil
44Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX

INTRODUCTION

Peripheral T-cell lymphomas (PTCL) is a rare and heterogeneous group of diseases in which risk-stratified approaches for managing patients (pts) with limited-stage (LS) PTCL remain unexplored. Although existing prognostic systems, such as the International Prognostic Index and the Prognostic Index for PTCL (PIT), have been used to predict outcomes, they lack impact on clinical decision-making. To refine the management of LS PTCL and improve prognostication, we developed a risk-stratified prognostic model and validated the findings in an independent external cohort.

METHODS

We included pts aged ≥18 years with newly diagnosed stage I-II PTCL. Subtypes were classified as anaplastic large cell lymphoma (ALCL, irrespective of ALK status) and non-ALCL (i.e., PTCL not otherwise specified [NOS], angioimmunoblastic T cell lymphoma and lymphomatous adult T cell leukemia/lymphoma [ATL]). Data for the training cohort was derived from the hospital-based registries of the Grupo de Estudio Latinoamericano de Linfoproliferativos and the Brazilian T-cell Project (median follow-up of 39 months). Data for the validation cohort was obtained from 2 academic centers in the United States (median follow-up of 53 months).

Overall survival (OS) was the primary endpoint of the score. We used Directed Acyclic Graphs to identify candidate variables reflecting patient fitness (ECOG performance status), disease activity (B symptoms, serum albumin and LDH levels and extranodal involvement), and disease biology (ALCL vs non-ALCL). Variables with a p-value <0.1 in an univariable Cox regression were included in a multivariable model. We used Kaplan-Meier and C-index to evaluate the discriminatory performance of the score compared to the PIT score.

RESULTS

The training cohort included 199 pts with LS PTCL who received first-line treatment with curative intent. The median age at diagnosis was 52 years (range 18-86) with a male predominance (59%) and good performance status (ECOG ≤1, 87%). B symptoms and extranodal involvement were present in 39% and 40%, respectively. ALK-negative ALCL (17%) and PTCL NOS (59%) were the most frequent subtypes within the ALCL and non-ALCL groups, respectively. CHOP (41%) was the most frequently used regimen. In the validation cohort, clinical features were similar, except a higher frequency of ALCL subtypes (49% vs 27%, p<0.001), lower frequency of extranodal involvement (16% vs. 40%, p<0.001), and a higher use of brentuximab vedotin-based regimens (35% vs. 3%, p<0.001).

Three factors were associated with OS in the multivariable Cox model, ECOG ≥2 (Hazard ratio [HR]=3.12, 95% confidence interval [CI]=1.61-6.05), B symptoms (HR=1.96 [1.16-3.32]) and non-ALCL subtype (HR=2.79 [1.25-6.23]). We used the HRs to assign points to the selected variables and developed a 2-risk group stratification model identifying pts with favorable (score 0-1) and unfavorable (score 2-6) prognoses. Pts with unfavorable risk had worse outcomes than those with favorable status (3-year OS 89% vs. 54%, p<0.001). The C-index was 0.602.

In the validation cohort (n=91), the score identified worse outcomes in pts with unfavorable features than those with favorable (3-year OS 97% vs. 64%, p=0.002), with better discriminatory performance than in the training cohort (C-index=0.690). Although the C-index of the PIT score was about 0.702 in both cohorts, the low sample sizes in the risk subgroups increased the uncertainty of estimates, and Kaplan-Meier curves overlapped. Sensitivity analysis excluding lymphomatous ATL cases did not affect score predictability on OS (p=0.002, C-index=0.605).

CONCLUSION

We have developed and validated a prognostic score for OS in LS PTCL pts reflecting patient fitness, disease activity, and biology. The 2-risk group scoring approach is practical for clinical use and may allow reproducibility in clinical studies. Notably, some pts with favorable status received less aggressive approaches, such as abbreviated courses of chemotherapy plus radiation therapy. Our model was developed in a setting of different PTCL epidemiology from Western countries, but the score maintained its prognostic value in the validation cohort from the United States. The score should be validated in prospective studies and among other Western and Asian populations. Our score may be used in clinical practice and trial designs to allocate pts with LS PTCL who may benefit from novel therapy approaches.

Disclosures: Oliver: Abbvie: Consultancy; Servier: Consultancy; Roche: Consultancy. De Farias: Libbs/mAbxcience: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Independent data monitoring committee, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau; Sanofi: Speakers Bureau; Pintfarma: Speakers Bureau; Knight Therapeutics/United Medical: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Europharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Viracta: Research Funding; Celltrion: Research Funding; MEDAC: Research Funding; Agios: Research Funding; Sandoz: Research Funding; Onconova: Research Funding; MSD: Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Zodiac: Speakers Bureau; AstraZeneca: Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Steering committee member, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Lilly: Research Funding; Regeneron: Research Funding; GSK: Research Funding. Iyer: Acrotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate: Research Funding; Merck: Research Funding; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Ono: Research Funding; IMPaRT.AI: Other: Stock, Founder; Crispr: Membership on an entity's Board of Directors or advisory committees, Research Funding; Salarius: Consultancy; Astra Zeneca: Research Funding; Trillium: Research Funding; Yingli: Membership on an entity's Board of Directors or advisory committees, Research Funding; Legend: Research Funding; Seagen/Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; JCO-CCI: Other: Editor. Nair: 280 Bio Inc.: Membership on an entity's Board of Directors or advisory committees. Castillo: Kite Pharmaceuticals: Consultancy; Janssen: Consultancy; Mustang Bio: Consultancy; Pharmacyclics: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Cellectar Biosciences: Consultancy, Research Funding.

*signifies non-member of ASH