Adam J Olszewski1, Lasse H Jakobsen2, Graham P Collins3, Kate Cwynarski4, Veronika Bachanova5, Kristie A Blum6, Kirsten M Boughan7, Mark Bower8, Alessia Dalla Pria8, Alexey Danilov9, Kevin A David10, Catherine Diefenbach11, Fredrik Ellin12, Narendranath Epperla13, Umar Farooq14, Tatyana A Feldman15, Alina S Gerrie16, Deepa Jagadeesh17, Manali Kamdar18, Reem Karmali19, Shireen Kassam20, Vaishalee P Kenkre21, Nadia Khan22, Seo-Hyun Kim23, Andreas K Klein24, Izidore S Lossos25, Matthew A Lunning26, Peter Martin27, Nicolas Martinez-Calle28, Silvia Montoto29, Seema Naik30, Neil Palmisiano31, David Peace32, Elizabeth H Phillips33, Tycel J Phillips34, Craig A Portell35, Nishitha Reddy36, Anna Santarsieri37, Maryam Sarraf Yazdy38, Knut B Smeland39, Scott E Smith40, Stephen D Smith41, Suchitra Sundaram42, Adam S Zayac1, Xiao-Yin Zhang3, Catherine Zhu4, Chan Y Cheah43, Tarec C El-Galaly44, Andrew M Evens10. 1. Lifespan Cancer Institute, The Warren Alpert Medical School of Brown University, Providence, RI. 2. Department of Haematology, Aalborg University Hospital, Aalborg, Denmark. 3. Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 4. Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom. 5. Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN. 6. Winship Cancer Institute, Emory University, Atlanta, GA. 7. Adult Hematologic Malignancies and Stem Cell Transplant Section, University Hospitals Seidman Cancer Center, Cleveland, OH. 8. National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, United Kingdom. 9. Toni Stephenson Lymphoma Center, City of Hope Comprehensive Cancer Center, Duarte, CA. 10. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. 11. Perlmutter Cancer Institute, NYU Langone Health, New York, NY. 12. Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden. 13. The Ohio State University James Comprehensive Cancer Center, Columbus, OH. 14. Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA. 15. John Theurer Cancer Center, Hackensack Meridian Health School of Medicine, Hackensack, NJ. 16. BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, British Columbia, Canada. 17. Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. 18. University of Colorado Cancer Center, Aurora, CO. 19. Division of Hematology Oncology, Northwestern University, Chicago, IL. 20. King's College Hospital, London, United Kingdom. 21. Carbone Cancer Center, University of Wisconsin, Madison, WI. 22. Fox Chase Cancer Center, Philadelphia, PA. 23. Division of Hematology Oncology, Rush University Medical Center, Chicago, IL. 24. Division of Hematology and Oncology, Tufts Medical Center, Boston, MA. 25. Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL. 26. University of Nebraska Medical Center, Omaha, NE. 27. Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY. 28. Nottingham University Hospitals, NHS Trust, Nottingham, United Kingdom. 29. Department of Haemato-oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom. 30. Penn State Cancer Institute, Penn State Hershey Medical Center, Hershey, PA. 31. Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA. 32. Division of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL. 33. Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 34. University of Michigan Comprehensive Cancer Center, Dexter, MI. 35. Division of Hematology/Oncology, University of Virginia, Charlottesville, VA. 36. Vanderbilt University Medical Center, Nashville, TN. 37. Department of Haematology, Cambridge University Hospitals NHSFT, Cambridge, United Kingdom. 38. Georgetown University Hospital, Washington, DC. 39. Department of Oncology, Oslo University Hospital, Oslo, Norway. 40. Loyola University Medical Center, Maywood, IL. 41. University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA. 42. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY. 43. Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia. 44. Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Abstract
PURPOSE: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
PURPOSE:Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.