Emily C Ayers1, Shaoying Li2, L Jeffrey Medeiros2, David A Bond3, Kami J Maddocks4, Pallawi Torka5, Angel Mier Hicks5, Madeira Curry6, Nina D Wagner-Johnston6, Reem Karmali7,8, Amir Behdad9, Bita Fakhri10, Brad S Kahl10, Michael C Churnetski11,12, Jonathon B Cohen11, Nishitha M Reddy13, Dipenkumar Modi14, Radhakrishnan Ramchandren15, Christina Howlett16, Lori A Leslie17, Samuel Cytryn18, Catherine S Diefenbach18, Rawan Faramand19, Julio C Chavez19, Adam J Olszewski20,21, Yang Liu22, Stefan K Barta1,22, Dhruvika Mukhija23, Brian T Hill24, Helen Ma25, Jennifer E Amengual26, Sunita Nathan27, Sarit E Assouline28, Victor M Orellana-Noia29, Craig A Portell30, Ashwin Chandar31, Kevin A David27, Anshu Giri32, Brian T Hess32, Daniel J Landsburg1. 1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Department of Hematopathology, The University of Texas MD Anderson Cancer, Houston, Texas. 3. Department of Internal Medicine, The Ohio State University Cancer Center, Columbus, Ohio. 4. Department of Hematology, The Ohio State University Cancer Center, Columbus, Ohio. 5. Roswell Park Comprehensive Cancer Center, Buffalo, New York. 6. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. 7. Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg. 8. School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois. 9. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Washington University School of Medicine, St. Louis, Missouri. 11. Department of Hematology, Winship Cancer Institute, Emory University, Atlanta, Georgia. 12. Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. 13. Department of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee. 14. Karmanos Cancer Institute/Wayne State University, Detroit, Michigan. 15. Hematology-Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, Michigan. 16. Deparrment of Pharmacy and Clinical Services, John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, New Jersey. 17. John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, New Jersey. 18. New York University Perlmutter Cancer Center, New York, New York. 19. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida. 20. The Warren Alpert Medical School of Brown University, Providence, Rhode Island. 21. Division of Hematology-Oncology, Rhode Island Hospital, Providence, Rhode Island. 22. Fox Chase Cancer Center, Philadelphia, Pennsylvania. 23. Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 24. Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 25. Center for Lymphoid Malignancies, Department of Medicine, and Department of Pathology and Cell Biology, Columbia University Medical Center , New York. 26. Division of Hematology and Oncology, Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York. 27. Rush University Medical Center, Chicago, Illinois. 28. Medicine and Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 29. University of Virginia, Charlottesville, Virginia. 30. Hematology and Oncology, University of Virginia, Charlottesville, Virginia. 31. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 32. Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
Abstract
BACKGROUND: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.
BACKGROUND: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS:Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.
Authors: Jillian F Wise; Sigve Nakken; Chloé B Steen; Daniel Vodák; Gunhild Trøen; Bjarne Johannessen; Ole Christian Lingjærde; Vera Hilden; Yngvild Nuvin Blaker; Baoyan Bai; Lars Birger Aasheim; Annika Pasanen; Susanne Lorenz; Anita Sveen; Ragnhild A Lothe; Ola Myklebost; Sirpa Leppä; Leonardo A Meza-Zepeda; Klaus Beiske; Michael S Lawrence; Eivind Hovig; June Helen Myklebust; Erlend B Smeland; Harald Holte Journal: Blood Adv Date: 2020-05-12
Authors: Esther K Elliott; Lloyd N Hopkins; Robert Hensen; Heidi G Sutherland; Larisa M Haupt; Lyn R Griffiths Journal: Front Genet Date: 2021-11-26 Impact factor: 4.599