Phase 2 study of anti-human cytomegalovirus monoclonal antibodies for prophylaxis in hematopoietic cell transplantation

Maertens J, Logan AC, Jang J, Long G, Tang JL, Hwang WY, Koh LP, Chemaly R, Gerbitz A, Winkler J, Yeh SP, Hiemenz J, Christoph S, Lee DG, Wang PN, Holler E, Mielke S, Akard L, Yeo A, Ramachandra S, Smith K, Pertel P, Segal F (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 64

Article Number: e02467-19

Journal Issue: 4

DOI: 10.1128/AAC.02467-19

Abstract

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation. As would be expected in the study population, all the patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study, and over 80% of the patients receiving placebo or CSJ148 developed at least one adverse event of grade 3 or higher severity. No subject who received antibody developed a hypersensitivity- or infusion-related reaction. CSJ148-treated patients showed trends toward decreased viral load, shorter median duration of preemptive therapy, and fewer courses of preemptive therapy. However, the estimated probability that CSJ148 decreases the need for preemptive therapy compared to placebo was 69%, with a risk ratio of 0.89 and a 90% credible interval of 0.61 to 1.31. The primary efficacy endpoint was therefore not met, indicating that CSJ148 did not prevent clinically significant HCMV reactivation in recipients of allogeneic hematopoietic cell transplants.

Authors with CRIS profile

Involved external institutions

National Taiwan University (NTU) Taiwan (TW) National University of Singapore (NUS) Singapore (SG) Franciscan Health Indianapolis United States (USA) (US) Duke University Medical Center United States (USA) (US) Universitätsklinikum Essen Germany (DE) Novartis Institutes for BioMedical Research, Inc. United States (USA) (US) UF Health Shands Cancer Hospital United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) UCSF Medical Center United States (USA) (US) Stat4ward LLC United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Seoul St. Mary's Hospital Korea, Republic of (KR) Universitätsklinikum Regensburg Germany (DE) China Medical University Hospital Taiwan (TW) Chang Gung Medical Foundation / 長庚醫療財團法人 / Chang Gung Memorial Hospital (CGMH) Taiwan (TW) Sungkyunkwan University (SKKU) Korea, Republic of (KR) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE)

How to cite

APA:

Maertens, J., Logan, A.C., Jang, J., Long, G., Tang, J.L., Hwang, W.Y.,... Segal, F. (2020). Phase 2 study of anti-human cytomegalovirus monoclonal antibodies for prophylaxis in hematopoietic cell transplantation. Antimicrobial Agents and Chemotherapy, 64(4). https://doi.org/10.1128/AAC.02467-19

MLA:

Maertens, Johan, et al. "Phase 2 study of anti-human cytomegalovirus monoclonal antibodies for prophylaxis in hematopoietic cell transplantation." Antimicrobial Agents and Chemotherapy 64.4 (2020).

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