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485 Characteristics and Outcomes of Newly Diagnosed Multiple Myeloma Patients with and without Extramedullary Disease after Autologous Transplant and Maintenance Therapy: A Study from the Cmwp-EBMT

Program: Oral and Poster Abstracts
Type: Oral
Session: 731. Autologous Transplantation: Clinical and Epidemiological I
Hematology Disease Topics & Pathways:
Clinical Research, Real World Evidence
Sunday, December 12, 2021: 1:00 PM

Nico Gagelmann1*, Dirk-Jan Eikema2*, Linda Koster3*, Tanja Netelenbos, MD, PhD4, Andrew McDonald, MD5*, Anne-Marie Stoppa, MD6, Guido Kobbe, MD7*, Achilles Anagnostopoulos8, Gwendolyn Van Gorkom9*, Eric Deconinck, MD, PhD10*, Claude-Eric Bulabois, MD11*, Michel Delforge12, Donald Bunjes, MD13*, William Arcese, MD, PhD14, Péter Reményi15*, Maija Itälä-Remes, MD, PhD16*, Lorenz Thurner, MD17*, Zahit Bolaman18*, Yafour Nabil19*, Stephan Mielke, MD20, Hélène Labussière-Wallet21*, Patrick J Hayden, MD22, Meral Beksac, MD23, Stefan Schönland24* and Ibrahim Yakoub-Agha25

1Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2Department of Statistics, Leiden University Medical Centre, Leiden, Netherlands
3EBMT Data Office, Leiden, Netherlands
4Hague Teaching Hospital, The Hague, Netherlands
5Alberts Cellular Therapy, Pretoria East Hospital, Pretoria, South Africa
6Institut Paoli Calmettes, Marseille, France
7Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
8Department of Hematology and HCT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
9Dept. Internal Med.Hematology /Oncology, University Hospital Maastricht, Maastricht, Netherlands
10Clinical Hematology, Besançon University Hospital, Besançon, France
11Service d'Hematologie, CHU Grenoble Alpes-Universite Grenoble Alpes, Grenoble, France
12University Hospital Leuven, Leuven, Belgium
13Department of Internal Medicine III, Bone Marrow Transplantation Unit, University Hospital of Ulm, Ulm, Germany
14Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
15St. István and St. László Hospital of Budapest, Budapest, Hungary
16Turku University Hospital, Stem cell transplantation unit, Turku, Finland
17Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
18Internal Medicine, Division of Hematology, Adnan Menderes University, Aydin, Turkey
19University Hospital of Oran, Oran, Algeria
20Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska Institute & University Hospital, Stockholm, Stockholms Laen, Sweden
21Service d’Hématologie, Hôpital Lyon Sud, Pierre Bénite, France
22Department of Haematology, St. James's Hospital, Dublin, Ireland
23Cebeci Yerleskesi Dikimevi, Ankara, Turkey
24Medical Department V, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, Germany
25Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, Lille, France

Patient selection becomes crucial for newly diagnosed multiple myeloma (NDMM), to identify those who may benefit the most from specific treatments. This is particularly important for patients for whom evidence of current treatment options remains very limited. One such subgroup is MM with extramedullary disease (EMD), especially those with organ manifestation. Maintenance therapy after autologous transplantation improves outcome for eligible NDMM patients, but randomized trials only included a small proportion of EMD patients, and to date, no adequate data exist on maintenance in this cohort. Here, we aimed to evaluate the characteristics and outcomes of NDMM with or without EMD after autologous transplant and maintenance therapy.

Cohorts were identified from NDMM patients undergoing first autologous transplant between 2008 and 2018. Involvement had to be documented as absent or present. Maintenance treatment was defined as single-agent treatment within 6 months after first autologous transplant without relapse. Outcomes were calculated from the start of maintenance therapy. Primary end points were progression-free survival (PFS) and overall survival (OS). Secondary end point was cumulative incidence of relapse.

In total, 830 NDMM patients with or without EMD were eligible, receiving either thalidomide (n=287), lenalidomide (n=446), bortezomib (n=75), or daratumumab (n=22; results for these patients will be presented at the meeting). 107 had EMD (n=83 paraskeletal and n=24 organ involvement). Maintenance drug distribution did not differ between NDMM with or without EMD (P=0.69) and is shown in Table 1. Fewer patients with organ involvement had IgA MM (23% vs 21% for no EMD and paraskeletal involvement, respectively). Patients with organ involvement more frequently were ISS stage III (50% vs 24% for no EMD and 15% for paraskeletal involvement).

The median follow-up of the entire cohort was 44 months (95% CI, 40-48 months). According to involvement, 3-year PFS was 52% (48-57%) for patients without EMD, 56% (44-69%) for paraskeletal involvement, and 45% (22-68%) for organ involvement (P=0.15). Of note, early outcome after maintenance start appeared to be significantly worse for organ involvement, with 1-year PFS of 58% vs 81% for paraskeletal involvement and 82% for no EMD. 3-year OS was 81% (77-84%) for no EMD, 88% (80-96%) for paraskeletal involvement, and 68% (47-89%) for organ involvement (p=0.06). Survival curves are depicted in Figure 1. Regarding relapse, organ involvement showed worse early 1-year cumulative incidence, with 42% vs 19% for paraskeletal involvement and 16% for no EMD.

In terms of maintenance therapy in patients without EMD, 3-year PFS was 45% (38-52%) for thalidomide, 59% (52-65%) for lenalidomide, 45% (31-59%) for bortezomib (P=0.005). 3-year OS was 79% (73-85%), 83% (78-88%), and 74% (61-87%; P=0.30). Relapse incidence was also significantly different showing lower relapse rates for lenalidomide (P=0.002).

In terms of maintenance therapy in patients with EMD, 3-year PFS was 52% (36-67%) for thalidomide, 43% (27-60%) for lenalidomide, 65% (32-97%) for bortezomib (P=0.90). Overall survival was 81% (69-93%) for thalidomide, 86% (76-97%) for lenalidomide, and 89% (68-100%) for bortezomib (P=0.70).

In multivariable analysis on PFS (including ISS, performance score, age, remission status) adjusting for early events at 1 year, organ involvement was significantly associated with worse early outcome (hazard ratio, 3.35; P=0.002) and showed no significant difference vs patients with no EMD after 1 year of follow-up. Paraskeletal involvement was not associated with different PFS. Lenalidomide was associated with significantly reduced risk for death or relapse/progression (hazard ratio, 0.69; P=0.003) vs thalidomide, and no difference was seen for bortezomib vs thalidomide. For OS, organ involvement appeared to be associated with worse outcome (hazard ratio 1.71; P=0.17), while no difference was seen for paraskeletal and no EMD. Lenalidomide (hazard ratio 0.72; P=0.05) and bortezomib (hazard ratio, 0.56; P=0.06) appeared to be associated with better OS.

In conclusion, organ involvement was associated with worse early PFS, despite maintenance treatment. Different maintenance treatment did not seem to affect outcome in EMD. For patients without EMD, lenalidomide showed significantly higher PFS compared with thalidomide.

Disclosures: McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kobbe: Celgene: Research Funding. Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials . Deconinck: Stemline Therapetutics: Membership on an entity's Board of Directors or advisory committees; Imunogen: Membership on an entity's Board of Directors or advisory committees; Chugai: Research Funding; Novartis: Research Funding; Pfizer: Other: Travel Grants, Research Funding; Abbevie: Research Funding. Delforge: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Thurner: Takeda: Honoraria; Abbvie: Other: Travel support; Janssen: Other: Travel support; EUSA-Pharma: Honoraria, Other: Travel Support; Astra-Zeneca: Honoraria; Merck: Honoraria. Mielke: DNA Prime SA: Speakers Bureau; Novartis: Speakers Bureau; Miltenyi: Other: Data safety monitoring board; Gilead/KITE: Other: Travel support, Expert panel ; Immunicum: Other: Data safety monitoring board; Celgene/BMS: Speakers Bureau. Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau. Schönland: Pfizer: Honoraria; Takeda: Honoraria, Other: Travel grants; Janssen: Honoraria, Other: Travel grants, Research Funding; Prothena: Honoraria, Other: Travel grants; Sanofi: Research Funding. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria.

*signifies non-member of ASH