Age: 63.0
Sex: M
Vaccine: COVID19
Symptoms: Red cell distribution width, Serum ferritin, White blood cell count
Clinical narrative: leukemia; A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS   This is a report from an interventional study source sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. The subject was in open-label phase of the study when the event occurred.   A 63-year-old male subject received blinded study vaccine (BNT162B2;PLACEBO) first dose on 29Aug2020 at 12:46 and second dose on 19Sep2020 at 09:12; the subject was unblinded to provide the opportunity of receiving COVID-19 vaccine per protocol and found to have received placebo. Then the subject received in open-label phase study vaccine BNT162B2, third dose on 11Jan2021 at 16:25 (Lot # P220395-020L) and fourth dose on 01Feb2021 at 16:06 (Lot# P220395-0068L), all via intramuscular (IM) route in left arm as single doses for COVID-19 immunization.  Ongoing medical history included diabetes mellitus type 2 from 1990, hypercholesterolemia from 2016, obesity from 2000, hypertension from 2010, sleep apnea from 2011, osteoarthritis knees from 2005, gastro esophageal reflux disease from 2018, coronary artery disease from 26Feb2021, worsening of elevated troponin level to 55 from 10Mar2021, productive cough from 01Mar2021. Additional medical history included pneumonia  from 18Feb2021 to 01Mar2021, non-ST elevation myocardial infarction on 26Feb2021 (AER 2021286057), coronary spasm from 08Mar2021 to 12Mar2021 (AER 2021286096), coronary blood stasis from 08Mar2021 to 12Mar2021 (AER 2021286096), elevated troponin level from 26Feb2021 to 10Mar2021. Family medical history relevant to adverse event included father-heart disease, mother-cancer, maternal grandmother-cancer, mother-osteoarthritis.  Ongoing concomitant medications included dulaglutide (TRULICITY) for diabetes mellitus type 2 from 2017, pravastatin for hypercholesterolemia from 2016, lisinopril for hypertension from 03Oct2020, dexlansoprazole (DEXILANT) for gastro esophageal reflux disease from 2018, fluticasone for seasonal allergies from 2017, cyanocobalamin for nutritional supplement from 2019, acetylsalicylic acid (ASPIRIN) for cardiovascular prophylaxis from 2015, vitamin D3 for nutritional supplement from 01Jan2021 and multivitamin for nutritional supplement from 2017. The subject had no concomitant vaccines or prior vaccinations (within 4 weeks).  The subject was diagnosed with leukemia on 18Mar2021, which was considered an important medical event and required a physician office and a visit to the emergency room. Clinical course was as follows: complete blood count (CBC) panel on 12Mar2021 (hospital discharge date for AER 2021286096) included:  white blood cell count (WBC) was 6.1 thousand/ul; cellular percentages were neutrophils 18%, lymphocytes 55%, monocytes 2%, basophils 0%, eosinophils 0 %, blasts 25% (low); absolute cell counts were absolute neutrophils 1098 cells/ul, low, absolute lymphocytes 3355 cells/ul, absolute monocytes 122 cells/ul, low, absolute basophils 0 cells/ul, absolute eosinophils 0 cells/ul, absolute blasts 1525 cells/ul; red blood cell count (RBC) was 2.81 million/ul (low), hemoglobin was 9.2 g/dl (low), hematocrit was 27.5% (low), mean cell volume (MCV) was 97.9 fl, mean cell hemoglobin (MCH) was 32.7 pg, mean cell haemoglobin concentration (MCHC) was 33.5 g/dl, red cell distribution width (RDW) was 14.7 %, platelet count was 129 thousand/ul (low), and mean platelet volume (MPV) was 9.5 fl.  Iron studies on 12Mar2021 were iron, total was 82 mcg/dl (low), iron binding capacity was 226 mcg/dl, % saturation was 38 mcg /dl, ferritin was 1396  ng/ml (high), and glucose was 163 mg/dl (high). Subject was referred to Oncology and had two bone marrow tests performed on 15Mar2021 and 25Mar2021. The doctors were testing the type of leukemia and the treatment options. Subject was scheduled to be admitted at hospital during the first week of April for 28 days. The action taken in response to the event for blinded study vaccine and study vaccine (BNT162B2) was not applicable (reported as dose not changed by the investigator). The outcome of the event was not recovered.   The investigator considered there was a reasonable possibility that the event leukemia was related to study vaccine (BNT162B2), while unrelated to blinded study vaccine, concomitant drugs or clinical trial procedure.; Sender's Comments: The event "Leukemia" is unlisted in the Single Reference Safety Document (SRSD) of the Investigational Product therapy vaccine (BNT162B2).  The company considers there is not a reasonable possibility that the event, leukemia, is related to vaccine administration based on the known adverse event profile of the suspect product and on the absence of a plausible pathophysiological mechanism by which the vaccine would be expected to cause this event.  Pfizer's safety database was reviewed for cases reporting PF-07302048 or blinded therapy through 15-MAR-2021 for adverse events encoding to MedDRA (v.23.1J) Preferred Term(s) of Leukaemia. Review of the database for the PT Leukaemia had the following results: 0 serious clinical trial cases (0 of which were attributed to therapy) and 2 non clinical trial cases.  The impacts of this report on the benefit/risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committee and Investigators, as appropriate.