Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

Robert F Cornell; Raphael Fraser; Luciano Costa; Stacey Goodman; Noel Estrada-Merly; Cindy Lee; Gerhard Hildebrandt; Usama Gergis; Nosha Farhadfar; César O Freytes; Rammurti T Kamble; Maxwell Krem; Robert A Kyle; Hillard M Lazarus; David I Marks; Kenneth Meehan; Sagar S Patel; Muthalagu Ramanathan; Richard F Olsson; John L Wagner; Shaji Kumar; Muzaffar H Qazilbash; Ninah Shah; Parameswaran Hari; Anita D'Souza

doi:10.1016/j.jtct.2020.11.018

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

Transplant Cell Ther. 2021 Mar;27(3):264.e1-264.e7. doi: 10.1016/j.jtct.2020.11.018. Epub 2020 Dec 16.

Authors

Robert F Cornell¹, Raphael Fraser², Luciano Costa³, Stacey Goodman⁴, Noel Estrada-Merly⁵, Cindy Lee⁶, Gerhard Hildebrandt⁷, Usama Gergis⁸, Nosha Farhadfar⁹, César O Freytes¹⁰, Rammurti T Kamble¹¹, Maxwell Krem⁷, Robert A Kyle¹², Hillard M Lazarus¹³, David I Marks¹⁴, Kenneth Meehan¹⁵, Sagar S Patel¹⁶, Muthalagu Ramanathan¹⁷, Richard F Olsson¹⁸, John L Wagner¹⁹, Shaji Kumar¹², Muzaffar H Qazilbash²⁰, Ninah Shah²¹, Parameswaran Hari⁵, Anita D'Souza²²

Affiliations

¹ AbbVie, North Chicago, Illinois.
² Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.
³ Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
⁴ Vanderbilt University Medical Center, Nashville, Tennessee.
⁵ Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁶ Royal Adelaide Hospital, Adelaide, South Australia, Australia.
⁷ Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
⁸ Department of Medical Oncology, Division of Hematological Malignancies, Thomas Jefferson University, Philadelphia, Pennsylvania.
⁹ Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL.
¹⁰ Texas Transplant Institute, San Antonio, Texas.
¹¹ Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
¹² Mayo Clinic Rochester, Rochester, Minnesota.
¹³ University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio.
¹⁴ Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom.
¹⁵ Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
¹⁶ Blood and Marrow Transplant Program, University of Utah, Salt Lake City, Utah.
¹⁷ Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, Massachusetts.
¹⁸ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
¹⁹ Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
²⁰ MD Anderson Cancer Center, Houston, Texas.
²¹ Division of Hematology-Oncology, University of California San Francisco, San Francisco, California.
²² Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: [email protected].

Abstract

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P < .01) and PFS (HR, .43; 95% CI, .26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

Keywords: Bone marrow transplant; Hem malignancies; Myeloma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amyloidosis*
Bortezomib / therapeutic use
Hematopoietic Stem Cell Transplantation*
Humans
Neoplasm Recurrence, Local
Plasma Cells

Substances

Bortezomib

Abstract

Publication types

MeSH terms

Substances

Grants and funding