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3348 Post-Transplant Cyclophosphamide for Graft Vs Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation: First Comparison By Donor Type; A Study from the Chronic Malignancies Working Party of the EBMT

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Non-Biological, Therapies, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Firoozeh Sahebi1*, Dirk-Jan Eikema2*, Linda Koster3*, Nicolaus Kröger4*, Ellen Meijer5*, Goda Choi6, Montserrat Rovira7*, Yener Koc8*, Emanuele Angelucci9*, Didier Blaise, MD10, Corrado Tarella11*, Andrew McDonald12*, Concepcion Herrera Arroyo13*, Noel Milpied14*, Luca Castagna15*, Friedrich Stoelzel, PD, MD16, Jaime Sanz Caballer, MD, PhD17*, Johanna Tischer18*, Fabio Ciceri19*, David Valcarcel20, Luigi Rigacci21*, Patrick J Hayden, MD22, Meral Beksac, MD23, Ibrahim Yakoub-Agha24 and Stefan Schonland25*

1City of Hope, Duarte, CA
2EBMT Statistical Unit, Leiden, Netherlands
3EBMT Data Office, Leiden, Netherlands
4University Hospital Eppendorf, Hamburg, Germany
5VU University Medical Center, Amsterdam, Netherlands
6University of Groningen, University Medical Center Groningen, Groningen, Netherlands
7Hospital Clinic, Dept. of Hematology, IDIBAPS, Barcelona, Spain, Barcelona, Spain
8Medicana International, Istanbul, Turkey
9Hematology and Transplant Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
10Institut Paoli Calmettes, Marseille, France
11European Institute of Oncology, Milan, Italy
12Netcare Pretoria East Hospital, Pretoria, South Africa
13Hospital Reina Sofia, Cordoba, Spain
14CHU Bordeaux, Pessac, France
15Transplantation Unit, Department of Oncology and Haematology, Instituto Clinico Humanitas, Milan, Italy
16Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
17Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Valencia, Spain
18LMU, Department of Internal Medicine III, University Hospital of Munich-Grosshadern, Munich, -, Germany
19Ospedale San Raffaele s.r.l., Milan, Italy
20Hematology Department, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Hospital Universitari, Barcelona, Spain
21Ospedale S. Camillo-Forlanini, Rome, Italy
22Department of Haematology, St. James's Hospital, Dublin, Ireland
23Ankara University School of Medicine, Department of Hematology, Ankara, Turkey
24Univ Lille, CHU de Lille, INFINITE, INSERM U1286, 59000 Lille, LILLE, France
25University Hospital Heidelberg, Heidelberg, Germany


Acute and chronic graft vs. host disease (a/cGVHD) are major causes of treatment failure and non-relapse mortality (NRM) in multiple myeloma (MM) patients (pts) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Use of post-transplant cyclophosphamide (PTCy) is now an established method for GVHD prophylaxis after HLA haplo-identical (haplo)-HCT. We previously reported data in MM pts undergoing haplo-HCT (EBMT/CIBMTR) and showed that PTCy was associated with promising overall survival (OS) (Sahebi et al., BBMT 2019). However, data using PTCy for GVHD prophylaxis in other donor types are very limited in MM.


We evaluated PTCy as GVHD prophylaxis in MM pts who underwent a first allo-HCT using matched related (MRD), matched unrelated (MUD), mismatched related or unrelated (MMRD/MMUD, one antigen), and haplo donors within EBMT centers. OS and progression free survival (PFS) were determined by means of the Kaplan-Meier estimator. Neutrophil and platelet engraftment, relapse and NRM, and a/cGVHD were analyzed individually in a competing risks framework with relapse and death as competing events. Cox proportional hazards regression was used in the multivariable analyses. All estimates include 95% confidence intervals. All included covariates are listed in the Table.

Patient Characteristics

Between 2012-2018, a total of 295 MM pts received PTCy as GVHD prophylaxis. Median age at transplant was 55 yrs. Allo-HCT was given at a median interval of 34.9 mo from MM diagnosis. The conditioning regimen included reduced intensity (RIC, 193, 65.4%) and myeloablative (MAC, 102, 34.6%). All pts except 10 (3.4%) had prior autologous HCT; all of these 10 pts received a haplo-HCT. GVHD prophylaxis included PTCy + cyclosporine A or tacrolimus +/- mycophenolate mofetil in the majority of patients (239, 81%), and this combination was used in nearly every patient with haplo-HCT. Overall, peripheral blood was used as the stem cell source in about 80% of pts, but bone marrow was used in nearly 40% of haplo-HCTs.

Results (Median and 95% confidence interval are provided)

  • 1) Median time to neutrophil engraftment was 19 d (18-19 d) with no apparent difference among donor types.
  • 2) Median time to platelet engraftment was 23 d (21-26 d), whereas haplo-HCT engraftments were longer (27 d (25-33 d)).
  • 3) NRM at 1 yr was 18% (12-22%) and at 2 yrs was 19% (14-24%), with no significant difference among different donor types. Age < 50 yrs significantly decreased NRM to 9% (2-16%, p=0.027) at 2 yrs.
  • 4) Cumulative incidence of grade II-IV aGVHD at +100 d was 30% (25-36%), and 1 yr cGVHD was 27% (21-32%), with no apparent difference among donor types.
  • 5) OS was 63% (57-69%) at 1 yr and 51% (45-58%) at 2 yrs for the whole group, with no statistical difference among different donor types after a median follow-up of 26.1 mo. Disease status at transplant < PR significantly decreased OS to 35% (22-47%, p=0.005) at 2 yrs.
  • 6) PFS was 42% (36-49%) at 1 yr and 26% (20-32%) at 2 yrs for the whole group without apparent significant difference among donor types. Disease status at transplant < PR significantly decreased PFS to 16% (6-26%, p=0.028) at 2 yrs.
  • 7) However, in multivariable analyses, donor type using haplo, HR 1.65 (0.56-1.67, p=0.03), was associated with increased mortality in addition to disease status at allo-HCT < PR, HR 1.93 (1.25-2.97, p=0.003). Finally, MUD was associated with an improved PFS, HR=0.63 (0.4-0.99, p=0.04). Disease status < PR, HR=1.85 (1.24-2.74, p=0.002) was again associated with inferior PFS.


PTCy in MM patients undergoing allo-HCT throughout donor types resulted in a low incidence of aGVHD grade II-IV of 30% and cGVHD of 27%, with OS of 51% and PFS of 26% at 2 yr. Our first donor comparison using PTCy revealed improved survival in matched (MRD and MUD) versus haplo allo-HCT after adjusting for other risk factors.

Disclosures: Blaise: Jazz Pharmaceuticals: Honoraria. Tarella: TG-therapeutics: Research Funding; ImmunoGen: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. McDonald: venetoclax advisory board in South Africa (in CLL context): Consultancy; Alberts Cellular Therapy: Current Employment. Milpied: Roche: Honoraria, Other: Travel support; Astellas: Honoraria; Gilead Sciences: Other: consultancy or advisory role; Celgene: Other: Travel support; Sandoz: Honoraria, Other: consultancy or advisory role; Janssen: Honoraria. Yakoub-Agha: Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria. Schonland: Janssen: Honoraria, Other: travel support to meetings, Research Funding; Prothena: Honoraria, Other: travel support to meetings, Research Funding; Takeda: Honoraria, Other: travel support to meetings, Research Funding.

*signifies non-member of ASH