-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3571 Outcomes and Management of Red Blood Cell Transfusions in Multiple Myeloma Patients Treated with Daratumumab

Basic Science and Clinical Practice in Blood Transfusion
Program: Oral and Poster Abstracts
Session: 401. Basic Science and Clinical Practice in Blood Transfusion: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Ajai Chari, MD1, Toshihisa Satta2*, Amit Tayal3*, Sundar Jagannath, MD4, Hearn Jay Cho, MD, PhD1, Samir Parekh, MD1, Kenneth Lau1*, Gillian Morgan1*, Donna Catamero5*, Juliet Escalon6*, Erika Florendo6*, Daniel Verina6*, Parul Doshi7*, Huaibao Feng8*, Clarissa Uhlar7*, Imran Khan8*, Tahamtan Ahmadi7, Peter M. Voorhees9, Maria-Victoria Mateos10 and Suzanne Arinsburg11*

1Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
2Department of Internal Medicine, Mount Sinai Beth Israel, New York, NY
3Department of Clinical Pathology, Mount Sinai Hospital, New York, NY
4Hematology and Medical Oncology, Mount Sinai Hospital, New York, NY
5The Mount Sinai Medical Center, New York, NY
6Ruttenberg Treatment Center, Mount Sinai Hospital, New York
7Janssen Research & Development, LLC, Spring House, PA
8Janssen Research & Development, LLC, Raritan, NJ
9Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
10University Hospital of Salamanca/IBSAL, Salamanca, Spain
11Blood Bank and Transfusion Services, Mount Sinai Hospital, New York, NY

Background
Daratumumab (DARA) is a human IgG1 kappa monoclonal antibody that targets cells expressing CD38, which is highly expressed in multiple myeloma (MM) cells. In the phase 2 MMY2002 (Sirius) trial, treatment with single agent DARA resulted in a 29% overall response rate, with a median PFS of 3.7 months in heavily pretreated MM patients (Lonial S. J Clin Oncol. 2015; 33(suppl): abstrLBA8512). However, CD38 is also expressed on red blood cells (RBCs) and DARA binding to RBCs results in pan-reactivity on RBC panel testing using an indirect antiglobulin test (IAT). Recently, it was reported that treating RBCs with dithiothreitol (DTT) removes DARA to allow for accurate antibody testing (Chapuy CI, et al. Transfusion. 2015;55(6pt2):1545-1554) but also denatures Kell antigen in the process. To date, little is known about the impact of DARA interference with IAT on the outcomes of patients requiring packed RBC (PRBC) transfusions.

Methods
The frequencies of PRBC transfusions and any transfusion-related adverse events from all 124 patients treated on the Sirius study were obtained from the clinical database as of the data cut off of January 9th, 2015. Although details of transfusions were not prospectively collected, surrogate outcomes of transfusion reactions within 4 weeks of the transfusion were analyzed including change in hemoglobin (Hb), elevated bilirubin, fever, and hypotension. In addition, we evaluated IAT results and transfusion outcomes of the 8 patients treated at our institution.

Results
During the study, 47 patients received 147 transfusions with a total of 235 units of PRBCs. To date, no transfusion-related reactions were noted. Of the 47 patients, 8 patients were treated at our institution. One patient showed multiple alloantibodies (anti-E, -K, -Jkb, -Fya, -Fy3, -S, Knops) on IAT prior to DARA. This individual and 6 others agglutinated all RBCs on panel testing with weak reactivity at the antihuman globulin phase of testing. Reactivity was enhanced by gel testing compared to reactivity in low ionic strength saline and was unaffected by enzymatic treatment with ficin. Six out of 7 patients had a negative autocontrol. The one patient with a positive autocontrol had a weakly positive direct antiglobulin test with IgG. Six out of these 7 patients with panagglutinin had a positive result on the first IAT after initiation of DARA, ranging from 7 to 175 days (median 49). One patient did not have an IAT after initiation of DARA.

A total of 9 leuko-reduced, irradiated, phenotypically matched RBCs were given to 3 patients during DARA treatment, and additional 9 units were given to 3 patients after DARA completion while their IATs remained positive. All transfusions resulted in an appropriate rise in Hb (median 1.0 g/dL, range 0.5—2.7) without any associated transfusion reactions. None of the patients made new unexpected RBC alloantibodies while receiving phenotypically matched RBCs.

Conclusion
For the 7 patients at our site with IAT testing after DARA treatment, all demonstrated pan-reactivity on RBC panel testing. Treatment with DTT removes this interference but also denatures Kell antigen in the process. Most hospitals do not use DTT as part of routine immunohematology workups; therefore, we recommend obtaining a red cell phenotype prior to initiating DARA treatment and providing phenotypically matched blood thereafter to avoid resultant difficulties in new alloantibody identification and delays in providing compatible PRBCs. Based on a database query of all 124 patients as well as all patients at our site, PRBC transfusions did not appear to be associated with complications. In a MM patient population that will frequently require PRBC transfusion, blood bank and hematologist/oncologist awareness of these findings is important to minimize errors or delays in providing compatible PRBCs.

Disclosures: Chari: Novartis: Consultancy , Research Funding ; Millennium/Takeda: Consultancy , Research Funding ; Celgene: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Onyx: Consultancy , Research Funding ; Biotest: Other: Institutional Research Funding ; Array Biopharma: Consultancy , Other: Institutional Research Funding , Research Funding . Jagannath: BMS: Other: Advisory Board ; Celgene: Other: Advisory Board ; Janssen: Other: Advisory Board . Catamero: Celgene: Honoraria , Other: Lecturer ; Onyx: Other: Lecturer ; Millennium / Takeda: Other: Lecturer . Verina: Celgene: Other: Lecturer . Doshi: Janssen: Employment . Feng: Janssen: Employment . Uhlar: Janssen: Employment . Khan: Janssen: Employment . Ahmadi: Janssen: Employment . Voorhees: Millennium/Takeda and Novartis: Honoraria ; Array Biopharma, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, and Oncopeptides: Consultancy ; Celgene, GlxoSmithKline, and Oncopeptides: Research Funding .

*signifies non-member of ASH