Blinatumomab induces complete response in refractory PTLD after hematopoietic cell transplantation

• Type of Material: Article
• Authors: Sanyukta Janardan, Emory University; Edwin Horwitz, Emory University; Ben Watkins, Emory University; Kirsten Williams, Emory University; Shanmuganathan Chandrakasan, Emory University; Muna Qayed, Emory University; Suhag Parikh, Emory University; Staci Arnold, Emory University; Frank Keller, Emory University; Adina Alazraki, Emory University; Michelle Schoettler, Emory University; Kathryn Leung, Emory University
• Language: English
• Date: 2022-05-24
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021006535
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 6
• Issue: 10
• Start Page: 3058
• End Page: 3061
• Keywords: Life Sciences & Biomedicine; Science & Technology; MULTIPLE-MYELOMA; Hematology; RISK; LENALIDOMIDE
• Research Categories: Health Sciences, Human Development; Health Sciences, Public Health

Abstract

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome and is related to defects in DNA repair pathways that predispose affected individuals to malignancies.1 Monomorphic posttransplant lymphoproliferative disorder (PTLD) is a rare complication of hematopoietic cell transplantation (HCT) and behaves like an aggressive malignancy, often treated with alkylator-based chemotherapy. The underlying DNA repair defect in FA increases susceptibility to significant HCT treatment-related morbidity and mortality and makes standard monomorphic PTLD therapy challenging. We hypothesized that the novel approach of blinatumomab immunotherapy would have efficacy against PTLD that expresses CD19, with minimal toxicity. A 6-year-old male with FA, FANCA subtype, received an HLA-C 1-allele mismatched unrelated donor bone marrow HCT for progressive pancytopenia without evidence of myelodysplasia that was unresponsive to androgen therapy. On pretransplant evaluation, he was immunoglobulin G (IgG)–negative for Epstein-Barr virus (EBV). The donor’s EBV serologic status was unknown. He was enrolled in a phase 2 clinical trial (registered on ClinicalTrials.gov as #NCT03924401) and, per protocol, received a preparative regimen of thymoglobulin (12 mg/kg), fludarabine (150 mg/m2), and cyclophosphamide (30 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included tacrolimus (serum target level, 8-12 ng/dL), mycophenolate mofetil through day 30, and the study drug abatacept on days −1, +5, +14, +28, +56, +87, +112, and +150. The patient had an uneventful early transplant course, with neutrophil engraftment on day +18. He was discharged on day +30 without evidence of GVHD and was on our institutional standard infectious prophylactic agents: acyclovir, Bactrim, and voriconazole at discharge.