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3403 Long Term Outcomes and Renal Response Following Autologous Stem Cell Transplantation for Light Chain Deposition Disease:a Retrospective Study on Behalf of the Cmwp of the EBMTClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Plasma Cell Disorders, Diseases, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Laurent Garderet, MD, PhD1*, Luuk Gras Sr., MD, PhD2*, Linda Koster3*, Montserrat Rovira, MD, PhD4*, Laure Vincent, MD5*, Guido Kobbe, MD6*, Srinivas Pillai7*, Dries Deeren, MD8, Martin Kaufmann, MD9, Jurgen Kuball, MD10, Hakan Ozdogu, MD11*, Maria Jesús Pascual12*, Jakob R. Passweg, MD, MS13, Adam Rye14*, Urpu Salmenniemi15*, John Snowden, MD16*, Thomas Stauffer Larsen17*, Xavier Leleu, MD18, Lauris Gastaud19*, Joanna Drozd-Sokolowska, MD, PhD20*, Kavita Raj, MD, PhD21, Meral Beksac, MD22, Stefan Schonland23*, Patrick John Hayden, MD24 and Donal P McLornan, MD, PhD21*

1Hôpital la pitié salpetriere, Paris, FRA
2EBMT Statistical Unit, Leiden, Netherlands
3EBMT Leiden Study Unit, Leiden, Netherlands
4Hospital clinic, Barcelona, Spain
5Department of Clinical Hematology, Montpellier University Hospital Center, Montpellier, France
6Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany
7University hospital of North Staffordshire, Stoke, United Kingdom
8AZ Delta, Roeselare, BEL
9Department of Hematology, Oncology and Palliative Care, Robert Bosch Hospital, Stuttgart, Germany
10Utrecht University, University Medical Centre, Utrecht, Netherlands
11Baskent University Hospital, Adana, TUR
12Hospital Regional de Málaga, Malaga, Spain
13Department of Hematology University Hospital of Basel, Basel, Switzerland
14Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, GBR
15Dept of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
16Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
17Department of Hematology, Odense University Hospital, Odense, Denmark
18Service D'Hématologie Et Thérapie Cellulaire, Poitiers, France
19Centre Antoine Lacassagne, Tourrettes-sur-Loup, France
20Central Clinical Hospital, The Medical University of Warsaw, Warsaw, Poland
21University College London Hospitals NHS Trust, London, United Kingdom
22Ankara University School of Medicine, Hematology Department, Ankara, Turkey
23University of Heidelberg, Heidelberg, Germany
24Department of Haematology, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland

Background: There is a paucity of data concerning long-term outcomes following autologous stem cell transplantation (ASCT) for light chain deposition disease (LCDD). The goal of this retrospective study was to analyze the outcomes following ASCT in LCDD patients in terms of toxicity and efficacy with both hematological and renal responses.

Methods: Adult patients who underwent a first ASCT for renal biopsy-proven LCDD (AL amyloidosis excluded) between the years 1995 and 2021 were selected from the EBMT registry. The probability of overall survival (OS) and progression-free survival (PFS) was estimated based on the Kaplan–Meier method and differences analyzed using the log-rank test. Engraftment with death as competing event and relapse and non-relapse mortality (NRM) were modeled using the crude cumulative incidence estimator and compared between groups with Gray’s test. eGFR, measured at auto-HCT and 3 6, and 12 months was longitudinally modeled using linear mixed effects models. Results: There were 51 patients in 24 centres. 63% were male. The median year of diagnosis was 2011 (IQR: 2008-2015). The underlying plasma cell disorder was either myeloma (47%) or Monoclonal Gammopathy of Clinical Significance (MGCS, 50%), with 3% missing. The median bone marrow aspirate plasmacytosis was 10% (IQR: 7.8-20) and the immunoglobulin isotypes were as follows: Light Chain only 69% (Kappa 82%, Lambda 18%), IgG 24%, IgA 2%, IgD 2% and non-secretory 2%. Of 17 patients with cytogenetic data, 3 were t(11;14) and one del 17p. All 40 patients with data on disease involvement had renal involvement, and, of these, 3 had cardiac and 2 hepatic involvement. At diagnosis, the median serum creatinine was 233 µmol/L (IQR:159-467), median proteinuria was 1,813 mg/24h (IQR:445-5974) and 16% had bone lesions. 42 of 44 patients with available data had received an induction regimen (93% bortezomib-based) and the hematological responses prior to transplant were as follows: CR 12%, VGPR 29%, PR 31%, MR/SD 16%, and relapse/progression 6% (missing: 6%). A total of 59% were transplanted in or after 2012. The median age at transplant was 55 years (IQR:49-61). The median time from diagnosis to transplant was 7.4 months (IQR:5.5-13.0) and 42% were on dialysis at the time of transplant. The Karnofsky Performance Score (KPS) was >80 in 79%. The Melphalan conditioning dose (mg/m2) was 100 (23%), 140 (55%) or 200 (21%). The median number of infused CD34+ cells x 106/kg was 3.4 (IQR:2.5-4.6) and 33% received G-CSF post-ASCT. A total of 13% received consolidation and 8% maintenance treatment post-ASCT. The median follow-up post-ASCT was 84 months (IQR:46-122). The median time to neutrophil engraftment was 12 days (IQR:11-13) and to platelet engraftment 13 days (11-16). The best hematological response at Day +100 post-ASCT (33% missing) was as follows: CR 44%, VGPR 26% and PR 29%. Mean eGFR at auto-HCT was 48.8 mL/min/1.73m2 (95% CI 36.8-60.8) in those not on dialysis and 15.2 mL/min/1.73m2 (95% CI 1.9-28.8) in those on dialysis (difference 33.6 mL/min/1.73m2, p<0.0001). In both groups there were no significant changes in eGFR after auto-HCT (p=0.99 and p=0.80, respectively). The box-plot figure shows eGFR at auto-HCT, and at 3, 6 and 12 months. At 6 years post-ASCT, OS was 88% (95% CI: 78-98%) and PFS was 44% (95% CI 28-60%). The median OS was not reached. The median PFS was 65 months (95% CI: 45-103). The 2-year cumulative relapse incidence was 17% (95% CI: 6-27%) and the 2-year cumulative incidence of NRM was 2% (95% CI: 0-6%). In univariate analysis, transplant from 2012 onwards was associated with a significantly superior OS (6-year OS 100 vs. 75%; log-rank p=0.05). There was a trend to superior OS in females (6-year OS 100 vs 82%, p=0.05). There was no significant association between KPS, Age, Disease Status at ASCT (VGPR or better vs. Other) or Dialysis Status at ASCT with any outcomes in this small cohort evaluation.

Conclusions: ASCT is a feasible option for patients with LCDD even though 42% were on dialysis at the time of transplantation. Overall outcomes are favourable with a low NRM and good long-term OS. There was no improvement in renal function.

Disclosures: Vincent: Pfizer: Other: Financing meeting participation; BMS, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation. Kobbe: MSD: Honoraria; Pfizer: Honoraria; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Gilead: Honoraria; BMS-Celgene: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Biotest: Honoraria; Takeda: Honoraria; Eurocept: Honoraria, Research Funding; Medac: Research Funding. Salmenniemi: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Immedia Pharma AB: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Viatris: Consultancy. Snowden: Janssen: Speakers Bureau; Sanofi: Speakers Bureau; Jazz: Speakers Bureau; Mallinckrodt: Speakers Bureau; Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees; advisory boards for MEDAC and Vertex, and clinical trial IDMC membership for Kiadis: Speakers Bureau; Advisory boards for Vertex: Speakers Bureau. Stauffer Larsen: BMS: Consultancy; Roche: Consultancy; Gilead: Consultancy; Novartis: Consultancy. Leleu: Harpoon Therapeutics: Honoraria; Janssen: Honoraria; Takeda: Honoraria; AbbVie: Honoraria; Merck: Honoraria; Amgen: Honoraria; Novartis: Honoraria; BMS/Celgene: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Beksac: Menarini: Other: Advisory Board; Takeda: Speakers Bureau; BMS: Speakers Bureau; Pfizer: Other: Advisory Board; Janssen: Other: Advisory Board, Speakers Bureau; Amgen: Speakers Bureau. McLornan: Jazz Pharma: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; UK ALL RIC TRIAL - DSM board: Other: participation on a data safety monitoring board or advisory board; EBMT Scientific Council Member: Other: Chair of EBMT CMWP; Imago Biosciences: Research Funding.

*signifies non-member of ASH