Treatment Use Study of Platelet Components Treated with Amotosalen and Ultraviolet a Light in Response to Emerging Arboviruses in Puerto Rico - True Study Final Results

Background: In 2014, epidemic chikungunya virus (CHIKV) emerged in Puerto Rico, concurrent with endemic dengue (DENV). The Department of Health mandated blood donation quarantine for 72h pending follow-up donor contact for infectious symptoms. The American Red Cross (ARC) halted local platelet collections and began importing blood components. Imported platelet components (PCs) from the continental U.S. were used to supply hospitals in the Caribbean. An alternative strategy is local PC production with amotosalen +UVA (A-UVA) pathogen reduction (PR) technology (INTERCEPT™ Blood System, Cerus Corporation, Concord, CA) as utilized by the French Transfusion Service in the Overseas Territories, including the Caribbean since 2007. The major logistical advantage of such a strategy is earlier PC availability to hospitals since there is no need to wait for the results of bacterial culture, or transport of PCs from the continental U.S. A-UVA technology inactivates bacteria, viruses, parasites and leukocytes by efficient covalent adduct modification of DNA and RNA, thus addressing risks of bacterial contamination and reducing the risk of transfusion-transmitted infection (TTI). Treatment with A-UVA also prevents transfusion associated graft vs. host disease (TA-GVHD) in an animal model, inhibits clonal T cell proliferation, prevents allogeneic antigen stimulation in mixed lymphocyte reactions, and inhibits transcription mediated cytokine production and early activation antigen expression (Corash et al, BMT 2004) and is recognized by the AABB as a replacement for gamma irradiation in the prevention of TA-GVHD.

Aims: A treatment use clinical study (TRUE) was conducted in Puerto Rico under the Investigational Device Exemption (IDE) early/expanded access regulations while the INTERCEPT Premarket approval (PMA) application was under review by the Food and Drug Administration (FDA). The objective of the TRUE study was to provide early access to INTERCEPT to reduce the risk of TTIs during the ongoing CHIKV/DENV epidemic.

Methods: A prospective, open label, single arm, treatment use, multi-center study was conducted involving 7 hospitals and the ARC. Apheresis (Trima^® or Amicus^® collectors) leukocyte-reduced PR PCs, suspended in 100% plasma without gamma irradiation, bacterial contamination testing, or the need for CMV serology were produced. Safety outcome measures included all adverse events (AEs), serious adverse events (SAEs) and acute transfusion reactions. Patients were transfused with study PCs according to local practices for as long as clinically indicated.

Results: 90 patients (55.6% male, mean age 67.2 y) were transfused with 256 PR PCs (2.8 ± 3.5/patient). The vast majority of the patients were hematology oncology patients (76.7%). Most patients (81.1%) received 1 transfusion cycle (transfusion support without > 5 days between transfusions) with 2 PR PCs (40.0%), while 32.2% received 1 PR PC, and 25.6% received between 3-10 PR PCs. Mean duration of platelet support was 14.7 days. Thirty-three unrelated AEs were reported in 26 patients. Nineteen patients (21.1%) had unrelated SAEs (including 17 deaths [18.9%]). Two febrile non-hemolytic reactions and one allergic transfusion reaction were reported and deemed unrelated to INTERCEPT by the investigators. No suspected cases of CHIKV or DENV infections or other TTIs were reported. Reported AEs were within the expected spectrum of co-morbidity and mortality for patients of similar age with advanced hematology-oncology diseases.

Conclusions: The INTERCEPT Blood System was rapidly deployed in response to the CHIKV and DENV epidemic with replacement of bacterial detection, gamma irradiation and the need for CMV serology. No PR PC related AEs were reported. INTERCEPT was approved in late 2014 by the FDA to treat Amicus apheresis PCs suspended in platelet additive solution and in 2016 for Trima PCs suspended in 100% plasma. The importance of this proactive technology is highlighted by the recent emergence of Zika virus (ZIKV). FDA has recently requested that all blood establishments in Puerto Rico and in certain counties in Florida cease collecting blood immediately until investigational donor screening test for ZIKV RNA is implemented or until they implement the use of an approved or investigational pathogen reduction technology.