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3325 Daratumumab after Allogeneic Hematopoietic Stem Cell Transplantation in Multiple Myeloma: Safety and Efficacy. a Retrospective Study from the Cmwp EBMT

Program: Oral and Poster Abstracts
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
antibodies, multiple myeloma, Biological, Diseases, Therapies, Plasma Cell Disorders, Lymphoid Malignancies
Monday, December 7, 2020, 7:00 AM-3:30 PM

Laure Vincent1,2*, Luuk Gras Sr.3*, Patrice Ceballos, MD, PhD4*, Jürgen Finke Sr., MD, PhD5, Jakob Passweg6*, Marie Robin, MD, PhD7, Laura Rosinol, MD, PhD8*, Monique C. Minnema9, Raphael Teipel, MD10*, JA Van Deosum11*, Mathias Haenel, MD12*, Pascal Lenain, MD13*, Edouard Forcade, MD, PhD14*, Christian Koenecke, MD15*, Sophie Ducastelle, MD16*, Jaime Sanz17*, Wilfried Schroyens, MD, PhD18, Tsila Zuckerman, MD19, Marco Ladetto, MD20, Linda Koster21*, Liesbeth C. de Wreede, PhD22*, Patrick J Hayden, MD23, Stefan Schönland, MD24*, Ibrahim Yakoub-Agha25 and Meral Beksac, MD26

1CHU Montpellier, Montpellier, France
2Hôpital Saint-Eloi, Montpellier, France
3EBMT Statistical Unit, Leiden, Netherlands
4Department of Hematology, Hopital St Eloi CHU de Montpellier, Montpellier, France
5University of Freiburg, Freiburg, Germany, Dept. of Hematology, Oncology and Stem Cell Transplantation,, Freiburg, Germany
6University Hospital Basel, Basel, Switzerland
7Hôpital Saint-Louis, APHP, Paris, France
8Hematology, Hospital Clinic i Provincial, Barcelona, Spain
9University Medical Center Utrecht, Utrecht, Netherlands
10Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
11University of Groningen, University Medical Center Groningen, Groningen, Netherlands
12Klinikum Chemnitz, Chemnitz, Germany
13Hematology department, Centre Henri Becquerel, Rouen, France
14Hôpital Haut-Levèque, Pessac, France
15Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
16Hematology department 1 G, Centre Hospitalier Lyon Sud, Pierre Benite, France
17Hospital Universitari I politècnic La Fe, VALENCIA, ESP
18Hematology, Antwerp University Hospital, Edegem, Belgium
19Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
20Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, ITA
21EBMT Data Office, Leiden, Netherlands
22Leiden University Medical Center, Leiden, Netherlands
23Department of Haematology, St. James's Hospital, Dublin, Ireland
24University of Heidelberg, Heidelberg, Germany
25Univ Lille, CHU de Lille, INFINITE, INSERM U1286, 59000 Lille, LILLE, France
26Cebeci Yerleskesi Dikimevi, Ankara, Turkey


Allogeneic stem cell transplantation (allo-HSCT) is a treatment option for high-risk multiple myeloma (MM), especially in patients who relapse early following auto-HSCT. Though there is a proven graft versus myeloma effect, relapse remains common. Daratumumab (Dara) is a humanized monoclonal anti-CD38 antibody approved for both newly diagnosed and relapsed MM. Its mechanisms of action include direct anti-MM activity (CDC, ADCC, ADCP, apoptosis induction) and indirect anti-MM activity depleting CD38+ immunosuppressive regulatory cells and promoting T-cell expansion and activation. The combination of its mechanism of action and lack of toxicity makes Dara a good candidate for use in the post-allo-HSCT setting. However, its immune effects (decrease in CD38-positive immune suppressor cells, including Tregs, NK cells, regulatory B cells, and myeloid-derived suppressor cells) may interfere with post-allo anti-MM effects. Nikolaenko et al (Clin Lymph Myeloma Leuk 2020) reported that aGVHD developed in five (15%) of 34 patients given Dara (mostly in combination) as treatment for post-allo relapse and the median PFS was 4.5 months.


We performed a retrospective study to evaluate the safety and efficacy of Dara post-allo-HSCT). Patients with MM having received at least one Dara infusion at any time after allo-HSCT were included. Key exclusion criteria were plasma cell leukemia and AL amyloidosis.


A total of 121 patients who received Dara after a first allo-HSCT were identified in the EBMT database. The year of allo-HSCT ranged from 2004 to 2019, median 2014. Allo-HSCT was performed at a median (range) of 34 (6-172) months after the diagnosis of myeloma. The stem cell source was PB in 89%, 37% were matched related donor and 39% matched unrelated donor. Conditioning was reduced intensity in 72% and myeloablative in 28%. Disease status at allo-HSCT was CR in 9%, VGPR in 35 %, PR in 43%, SD/MR in 7% and progression in 6%.

The median age (range) at the first Dara infusion was 55 (32-71) yrs with a male to female distribution of 70/51. Dara was administered either alone (n=70) or in combination with other anti-myeloma directed therapy (n=51). The first dose of Dara was given at a median (range) of 30 (1-173) months post-allo-HSCT. Fifteen patients started Dara in the first 6 months after allo-HSCT, 50% of patients in the first 2.5 years, 22% in 2.5 to 5 years, and 28% more than five years after allo-HSCT.

Among patients with available data, 45% had at least one serious infection: bacteremia 22% (including 15% ³ grade 3), septic shock 5% (all ³ grade 3), pneumonia 31% (including 21% ³ grade 3), urine infections 7%, CMV reactivation 7% and EBV reactivation 6%.

In the first 100 days after starting Dara, aGVHD worsened in 2% (0-4%). The incidence of cGvHD within two years was 5% (1-9%).

Dara had been stopped due to adverse events in 10% (95% CI 5-16%) by 24 months. At the same timepoint, 70% (60-79%) of patients had stopped because of progression.

The best response to Dara was sCR/CR in 11%, VGPR in 12%, PR in 25%, SD/MR in 20% and progression in 33%. The best response was obtained at a median of 81 days (min-max 7-851 days) after starting Dara. The proportion of at least stable disease was higher when DLI treatment (n=37) was given pre-Dara.

The median follow-up from the first dose of Dara was 26.8 months (95% CI 22.3 to 31.1). After starting Dara, the median PFS was 6.5 months, the median TTNT 19.3 months and median OS 21.6 months.

Extra-medullary progression post-Dara was observed in 43% of patients for whom there was available data. Bone plasmacytomas were reported in 63%, soft tissues in 33% and both in 4% of cases.

In total 13% of patients received a median of two DLI after starting Dara. 47% of patients received other anti-myeloma medications after Dara and 26% received radiotherapy.


The use of Dara post-allo-HSCT resulted in stable disease or better in 67% of patients. As reported previously, infections appeared to be common. Compared to the recently published data from Nikolaenko et al, there were fewer cases of aGVHD post-Dara in this retrospective analysis. The PFS were similar in both studies (4.5 vs. 6.5 months) as well as OS (17,4 v 21,6 months). A high proportion of 43% extra-medullary disease progression was observed in the current study which was not reported in the only similar study. Based on these data, Dara treatment for relapsing patients after allo-HCT creates no safety concerns and provides acceptable efficacy

Disclosures: Vincent: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; janssen: Membership on an entity's Board of Directors or advisory committees, Other: Congress support. Minnema: Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding; Amgen: Consultancy; Servier: Consultancy. Teipel: janssen: Honoraria. Haenel: Amgen, Novartis, Roche, Celgene, Takeda, Bayer: Honoraria. Forcade: JAZZ: Other: Travel grant for congress; NEOVII: Other: Travel grant for congress; Gilead: Speakers Bureau; Sanofi: Other: Travel grant for congress; Novartis: Other: Travel grant for congress. Schönland: Janssen, Prothena, Takeda: Honoraria, Other: travel support to meetings, Research Funding. Yakoub-Agha: Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria. Beksac: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen&janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Deva: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

*signifies non-member of ASH