Abstract
The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4–11%), relapse (REL) 76% (69–82%), progression-free survival (PFS) 17% (13–23%), and overall survival (OS) 28% (22–35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5–21%), REL 69% (56–81%), PFS 19% (10–31%), and OS 31% (19–44%). Compared with prior CIBMTR pPCL patients (1995–2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7–21%) in 1995 to 46% (34–64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.
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Change history
05 June 2021
A Correction to this paper has been published: https://doi.org/10.1038/s41375-021-01304-3
29 March 2021
A Correction to this paper has been published: https://doi.org/10.1038/s41375-021-01233-1
References
Fernandez de Larrea C, Kyle RA, Durie BG, Ludwig H, Usmani S, Vesole DH, et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia. 2013;27:780–91.
Tiedemann RE, Gonzalez-Paz N, Kyle RA, Santana-Davila R, Price-Troska T, Van Wier SA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia. 2008;22:1044–52.
Kyle RA, Maldonado JE, Bayrd ED. Plasma cell leukemia. Report on 17 cases. Arch Intern Med. 1974;133:813–8.
Noel P, Kyle RA. Plasma cell leukemia: an evaluation of response to therapy. Am J Med. 1987;83:1062–8.
Ramsingh G, Mehan P, Luo J, Vij R, Morgensztern D. Primary plasma cell leukemia: a surveillance, epidemiology, and end results database analysis between 1973 and 2004. Cancer. 2009;115:5734–9.
Gonsalves WI, Rajkumar SV, Go RS, Dispenzieri A, Gupta V, Singh PP, et al. Trends in survival of patients with primary plasma cell leukemia: a population-based analysis. Blood. 2014;124:907–12.
Mahindra A, Kalaycio ME, Vela-Ojeda J, Vesole DH, Zhang MJ, Li P, et al. Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research. Leukemia. 2012;26:1091–7.
Usmani SZ, Nair B, Qu P, Hansen E, Zhang Q, Petty N, et al. Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. Leukemia. 2012;26:2398–405.
Jurczyszyn A, Radocha J, Davila J, Fiala MA, Gozzetti A, Grzasko N, et al. Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients. Br J Haematol. 2018;180:831–9.
Drake MB, Iacobelli S, van Biezen A, Morris C, Apperley JF, Niederwieser D, et al. Primary plasma cell leukemia and autologous stem cell transplantation. Haematologica. 2010;95:804–9.
D’Arena G, Valentini CG, Pietrantuono G, Guariglia R, Martorelli MC, Mansueto G, et al. Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party. Ann Oncol. 2012;23:1499–502.
Gowda L, Shah M, Badar I, Bashir Q, Shah N, Patel K, et al. Primary plasma cell leukemia: autologous stem cell transplant in an era of novel induction drugs. Bone Marrow Transpl. 2019;54:1089–93.
Mina R, Joseph NS, Kaufman JL, Gupta VA, Heffner LT, Hofmeister CC, et al. Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents. Cancer. 2019;125:416–23.
Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, et al. Bortezomib, doxorubicin, cyclophosphamide, dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the intergroupe francophone du myelome. J Clin Oncol. 2016;34:2125–32.
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–e46.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.
Lebovic D, Zhang L, Alsina M, Nishihori T, Shain KH, Sullivan D, et al. Clinical outcomes of patients with plasma cell leukemia in the era of novel therapies and hematopoietic stem cell transplantation strategies: a single-institution experience. Clin Lymphoma Myeloma Leuk. 2011;11:507–11.
Katodritou E, Terpos E, Kelaidi C, Kotsopoulou M, Delimpasi S, Kyrtsonis MC, et al. Treatment with bortezomib-based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group. Am J Hematol. 2014;89:145–50.
Benson DM Jr., Smith MK. Effectiveness of lenalidomide (Revlimid) for the treatment of plasma cell leukemia. Leuk Lymphoma. 2007;48:1423–5.
Guglielmelli T, Merlini R, Giugliano E, Saglio G. Lenalidomide, melphalan, and prednisone association is an effective salvage therapy in relapsed plasma cell leukaemia. J Oncol. 2009;2009:867380.
Vela-Ojeda J, Garcia-Ruiz Esparza MA, Rosas-Cabral A, Padilla-Gonzalez Y, Garcia-Chavez J, Tripp-Villanueva F, et al. Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Ann Hematol. 2002;81:362–7.
Grassinger J, Sudhoff T, Andreesen R, Hennemann B. Complete remission and successful stem cell mobilization after treatment of refractory plasma cell leukemia with bortezomib. Ann Hematol. 2006;85:132–3.
Esparis-Ogando A, Alegre A, Aguado B, Mateo G, Gutierrez N, Blade J, et al. Bortezomib is an efficient agent in plasma cell leukemias. Int J Cancer. 2005;114:665–7.
Gowda L, Shah M, Badar I, Bashir Q, Shah N, Patel K, et al. Primary plasma cell leukemia: autologous stem cell transplant in an era of novel induction drugs. Bone Marrow Transplant. 2019;54:1089–93.
Musto P, Simeon V, Martorelli MC, Petrucci MT, Cascavilla N, Di Raimondo F, et al. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia. Leukemia. 2014;28:222–5.
Lawless Sea. Comparison of haematopoietic stem cell transplantation approaches in primary plasma cell leukaemia. Blood. 2016;128:2293.
Avet-Loiseau H, Roussel M, Campion L, Leleu X, Marit G, Jardel H, et al. Cytogenetic and therapeutic characterization of primary plasma cell leukemia: the IFM experience. Leukemia. 2012;26:158–9.
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28:4184–90.
Gertz MA. Managing plasma cell leukemia. Leuk Lymphoma. 2007;48:5–6.
Chang H, Qi X, Yeung J, Reece D, Xu W, Patterson B. Genetic aberrations including chromosome 1 abnormalities and clinical features of plasma cell leukemia. Leuk Res. 2009;33:259–62.
Chiecchio L, Dagrada GP, White HE, Towsend MR, Protheroe RK, Cheung KL, et al. Frequent upregulation of MYC in plasma cell leukemia. Genes Chromosomes Cancer. 2009;48:624–36.
Kumar S, Kaufman JL, Gasparetto C, Mikhael J, Vij R, Pegourie B, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130:2401–9.
Gonsalves WI, Buadi FK, Kumar SK. Combination therapy incorporating Bcl-2 inhibition with Venetoclax for the treatment of refractory primary plasma cell leukemia with t (11;14). Eur J Haematol. 2018;100:215–7.
Jelinek T, Mihalyova J, Kascak M, Duras J, Popkova T, Benkova K, et al. Single-agent venetoclax induces MRD-negative response in relapsed primary plasma cell leukemia with t(11;14). Am J Hematol. 2019;94:E35–E7.
Acknowledgements
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NHLBI and NCI; U01HL128568 from the NHLBI; HHSH250201700006C, and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, UG1HL06924, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Farber, St. Baldrick’s Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.
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The following authors have conflict of interest: BD reports honorarium from Celgene; Advisory board for Takeda and Amgen. HML reports Bristol Myers Squibb and Celgene. RPG reports Celgene Corporation. KS-G reports Abbot and AbbVie. AA reports research funding from Incyte Corporation; Advisory board for Boston Biomedical and Incyte Corporation. Consulting for Alpha Insights. LH reports Up-To-Date. NS reports funding from Celgene, Bluebird Bio, Sutro Biopharma; Advisory role for Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision Biosciences, GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi; Stock Ownership for Indapta Therapeutics. ADS reports funding from Merck, Prothena, Sanofi, Mundipharma EDO, TeneoBio, Takeda and has received consulting fees from Prothena, Pfizer, Imbrium, and Akcea.
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The original online version of this article was revised: The acknowledgement of the original article was incomplete. Correct is should read: The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NHLBI and NCI; U01HL128568 from the NHLBI; HHSH250201700006C, and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, UG1HL06924, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Farber, St. Baldrick’s Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.
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Dhakal, B., Patel, S., Girnius, S. et al. Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era. Leukemia 34, 3338–3347 (2020). https://doi.org/10.1038/s41375-020-0830-0
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