Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma–type Richter syndrome

Author:

Herrera Alex F.1ORCID,Ahn Kwang Woo23ORCID,Litovich Carlos2,Chen Yue3,Assal Amer4ORCID,Bashir Qaiser5ORCID,Bayer Ruthee-Lu6,Coleman Melanie7,DeFilipp Zachariah8ORCID,Farhadfar Nosha9,Greenwood Matthew10ORCID,Hahn Theresa11,Horwitz Mitchell12,Jacobson Caron13,Jaglowski Samantha14ORCID,Lachance Sylvie15,Langston Amelia16ORCID,Mattar Bassam17,Maziarz Richard T.18,McGuirk Joseph19ORCID,Mian Mohammad A. H.20,Nathan Sunita21,Phillips Adrienne22,Rakszawski Kevin23,Sengeloev Henrik24,Shenoy Shalini25,Stuart Robert26,Sauter Craig S.2728,Kharfan-Dabaja Mohamed A.29ORCID,Hamadani Mehdi2ORCID

Affiliation:

1. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA;

2. Center for International Blood and Marrow Transplant Research, Department of Medicine, and

3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI;

4. Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, New York, NY;

5. Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX;

6. North Shore University Hospital, Northwell Health Cancer Institute, Long Island, NY;

7. Indiana Blood & Marrow Transplantation, Indianapolis, IN;

8. Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA;

9. Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL;

10. Royal North Shore Hospital, St. Leonards, NSW, Australia;

11. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY;

12. Duke University Medical Center, Durham, NC;

13. Dana Farber Cancer Institute, Boston, MA;

14. Division of Hematology, The Ohio State University Medical Center, Columbus, OH;

15. Institut Universitaire d’Hémato-Oncologie et Thérapie Cellulaire, Université de Montréal, Montréal, QC, Canada;

16. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA;

17. Ascension Via Christi Hospitals, Wichita, KS;

18. Adult Blood and Marrow Stem Cell Transplant Program, Knight Cancer Institute, Oregon Health and Science University, Portland, OR;

19. Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Kansas City, KS;

20. Georgia Cancer Center, Augusta University Medical Center, Augusta, GA;

21. Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center; Chicago, IL;

22. New York Presbyterian Hospital at Cornell, Weill Cornell Medical College, New York, NY;

23. Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA;

24. University Hospital, Rigshospitalet, Denmark;

25. Washington University/St. Louis Children's Hospital, St. Louis, MO;

26. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC;

27. Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY;

28. Department of Medicine, Weill Cornell Medical College, New York, NY; and

29. Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL

Abstract

Abstract Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P < .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.

Publisher

American Society of Hematology

Subject

Hematology

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