Table 3. Data Associated With PTs With a Disproportionality EB05 Score of 2.0 or Higher Grouped by SOC for US Adverse Event Reports Submitted to the US FDA Adverse Event Reporting System for Sipuleucel-T, Overall and According to Seriousness, April 29, 2010, to December 31, 2017.
| SOC and PT | All Reportsa,b | Serious Reports Only | Labeled Eventc | ||
|---|---|---|---|---|---|
| No. | EBGM (90% CI) | No. | EBGM (90% CI) | ||
| Blood and lymphatic system disorders | |||||
| Anemia | 125 | 3.0 (2.6-3.5) | 119 | 2.9 (2.5-3.3) | Yes |
| Leukocytosis | 15 | 4.1 (2.7-6.0) | 14 | 3.4 (2.2-5.1) | No |
| Normochromic normocytic anemia | 6 | 6.5 (2.7-26.6) | 6 | 5.1 (2.4-17.0) | Yes |
| Anemia of chronic disease | 6 | 4.9 (2.4-12.2) | 6 | 4.4 (2.3-9.1) | Yes |
| Cardiac disordersd | |||||
| Tachycardia | 42 | 4.8 (3.7-6.1) | 33 | 3.7 (2.8-4.9) | Yes |
| Sinus tachycardia | 8 | 3.8 (2.1-6.3) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Gastrointestinal disorders | |||||
| Vomiting | 140 | 2.7 (2.4-3.1) | 97 | 2.7 (2.3-3.2) | Yes |
| Oral paresthesia | 9 | 4.2 (2.5-6.9) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Nausea | Lower scoree | Lower scoree | 125 | 2.4 (2.1-2.8) | Yes |
| General disorders and administration site conditions | |||||
| Chills | 317 | 15.8 (14.4-17.3) | 166 | 13.0 (11.4-14.8) | Yes |
| Malaise | 192 | 3.1 (2.8-3.5) | 114 | 3.3 (2.8-3.8) | No |
| Pyrexia | 191 | 4.5 (4.0-5.1) | 120 | 3.5 (3.0-4.0) | Yes |
| Feeling cold | 16 | 3.1 (2.1-4.6) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infusion site extravasation | 14 | 8.2 (4.6-17.1) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| SIRS | 11 | 8.0 (4.1-19.3) | 11 | 6.8 (3.7-16.0) | No |
| Complication associated with device | 10 | 4.0 (2.4-6.4) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infusion site pain | 7 | 3.9 (2.1-6.6) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infusion site swelling | 6 | 4.4 (2.3-8.4) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Catheter site pain | 5 | 4.5 (2.1-12.0) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infusion site hematoma | 5 | 28.4 (3.8-82.8) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infusion site reaction | 5 | 5.9 (2.3-28.7) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Infections and infestations | |||||
| Device-related infection | 110 | 29.9 (25.5-34.8) | 94 | 24.2 (20.4-28.6) | Yes |
| Urinary tract infection | 88 | 3.8 (3.2-4.5) | 70 | 3.3 (2.7-4.0) | Yes |
| Infection | 64 | 3.4 (2.7-4.1) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Sepsis | 62 | 2.8 (2.3-3.4) | 62 | 2.6 (2.1-3.2) | Yes |
| Bacteremia | 24 | 7.6 (5.2-11.6) | 23 | 6.6 (4.6-9.6) | Yes |
| Staphylococcal bacteremia | 22 | 22.5 (15.5-31.8) | 22 | 19.6 (13.4-27.8) | Yes |
| Device-related sepsis | 20 | 48.9 (33.2-69.9) | 20 | 42.9 (29.2-61.3) | Yes |
| Catheter site infection | 10 | 5.2 (3.1-8.6) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Staphylococcal sepsis | 8 | 4.7 (2.6-8.0) | 8 | 4.2 (2.4-7.0) | Yes |
| Injury, poisoning, and procedural complications | |||||
| Infusion-related reaction | 65 | 12.1 (9.4-15.3) | 47 | 9.3 (6.9-12.6) | Yes |
| Citrate toxicity | 16 | 153.1 (99.1-228.1) | 11 | 130.0 (76.4-209.9) | Yes |
| Investigations | |||||
| Culture positive | 180 | 157.1 (138.8-177.4) | 50 | 111.5 (87.8-140.0) | Yes |
| Hemoglobin decreased | 91 | 3.4 (2.9-4.1) | 74 | 2.8 (2.3-3.4) | Yes |
| Blood pressure decreased | 48 | 3.6 (2.8-4.5) | 34 | 3.4 (2.5-4.4) | Yes |
| Mononuclear cell count abnormal | 39 | 161.6 (123.1-209.1) | 5 | 71.4 (29.9-149.7) | Noe |
| Hematocrit decreased | 33 | 5.4 (4.1-7.1) | 30 | 4.8 (3.5-6.4) | Yes |
| Body temperature increased | 32 | 10.0 (6.8-14.9) | 24 | 8.2 (5.4-13.3) | Yes |
| Microbiology test abnormal | 21 | 154.3 (105.9-218.6) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Staphylococcus test positive | 13 | 12.3 (5.4-24.5) | 12 | 7.5 (4.0-17.2) | Yes |
| Neutrophil count abnormal | 7 | 5.7 (2.8-17.2) | EB05 < 2.0 | EB05 < 2.0 | No |
| Blood culture positive | 6 | 4.3 (2.2-7.8) | 6 | 3.9 (2.0-6.9) | Yes |
| Gram stain positive | 4 | 17.0 (2.4-87.7) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Metabolism and nutrition disorders | |||||
| Dehydration | 106 | 3.1 (2.6-3.6) | 93 | 2.7 (2.3-3.2) | No |
| Hyponatremia | 28 | 3.9 (2.8-5.2) | 28 | 3.5 (2.6-4.8) | No |
| Hypokalemia | 22 | 4.3 (3.0-6.0) | 22 | 3.9 (2.7-5.4) | No |
| Malnutrition | 12 | 4.1 (2.5-6.3) | 12 | 3.8 (2.4-5.7) | No |
| Hypovolemia | 11 | 4.2 (2.6-6.6) | 11 | 3.8 (2.4-5.9) | No |
| Musculoskeletal and connective tissue disorders | |||||
| Back pain | 111 | 2.8 (2.4-3.2) | 69 | 2.9 (2.4-3.6) | Yes |
| Bone pain | 32 | 3.9 (2.9-5.2) | 24 | 4.6 (3.3-6.3) | Yes |
| Nervous system disordersf | |||||
| Tremor | 66 | 2.6 (2.1-3.2) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Transient ischemic attack | 30 | 2.9 (2.2-3.9) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Unresponsive to stimuli | 25 | 3.3 (2.4-4.5) | 24 | 2.9 (2.0-3.9) | No |
| Presyncope | 20 | 3.6 (2.5-5.1) | 17 | 3.4 (2.3-4.9) | Yes |
| Carotid artery stenosis | 7 | 3.8 (2.1-6. 6) | EB05 < 2.0 | EB05 < 2.0 | No |
| Product | |||||
| Thrombosis in device | 23 | 27.7 (19.3-38.7) | 11 | 6.3 (3.5-14.0) | Yes |
| Device occlusion | 18 | 7.3 (4.7-12.4) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Product contamination microbial | 7 | 8.6 (3.2-30.1) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Product sterility lacking | 5 | 44.7 (5.9-106.6) | 5 | 36.3 (4.6-91.5) | Yes |
| Renal and urinary disorders | |||||
| Hematuria | 48 | 3.1 (2.4-3.9) | 46 | 3.2 (2.5-4.0) | Yes |
| Respiratory, thoracic, and mediastinal disorders | |||||
| Pulmonary embolism | 52 | 3.1 (2.4-3.8) | 52 | 2.7 (2.2-3.4) | Yes |
| Atelectasis | 23 | 6.2 (4.4-8.7) | 23 | 5.3 (3.8-7.4) | No |
| Hypoxia | 22 | 2.9 (2.1-4.1) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Surgical and medical procedures | |||||
| Hospitalization | 105 | 5.1 (4.3-5.9) | 105 | 4.6 (3.9-5.4) | Outcome |
| Hospice care | 15 | 5.0 (3.3-7.5) | 10 | 3.8 (2.3-6.1) | Outcome |
| Vascular disorders | |||||
| Deep vein thrombosis | 53 | 3.2 (2.6-4.0) | 53 | 2.9 (2.3-3.6) | Yes |
| Pallor | 30 | 7.5 (5.4-10.4) | 18 | 4.9 (3.3-7.0) | No |
| Hematoma | 26 | 3.6 (2.6-4.9) | EB05 < 2.0 | EB05 < 2.0 | Yes |
| Poor venous access | 22 | 36.0 (24.9-50.6) | 8 | 26.6 (7.9-50.9) | Yes |
| Thrombophlebitis superficial | 8 | 6.1 (3.1-16.9) | 8 | 5.5 (2.9-13.9) | Yes |
| Jugular vein thrombosis | 7 | 16.9 (4.1-45.0) | 7 | 13.6 (3.6-39.0) | Yes |
Abbreviations: EBGM, empirical Bayes Geometric Mean; EB05, lower bound of EBGM 90% CI; FDA, Food and Drug Administration; PT, preferred term; SIRS, systemic inflammatory response syndrome; SOC, system organ class.
The following PTs (all reports) within the specified SOC had an EB05 of 2.0 or higher but were not included in the table because there is potential confounding by the following indications. General disorders and administration site conditions: disease progression (n = 139); investigations: prostate-specific antigen increased (n = 66), blood alkaline phosphate increased (n = 23); neoplasms: prostate cancer (n = 52), prostate cancer metastatic (n = 49), metastases to bone (n = 45), metastases to central nervous system (n = 20), neoplasm progression (n = 18), metastases to liver (n = 17), metastasis (n = 13), metastases to spine (n = 7), metastases to lymph nodes (n = 6), and metastases to meninges (n = 6); nervous system disorders: spinal cord compression (n = 23); and renal disorders: hydronephrosis (n = 24), urinary tract obstruction (n = 8), ureteric obstruction (n = 7), bladder obstruction (n = 7). Although back pain, bone pain, and hematuria could also be associated with confounding by indication, these symptoms and signs are also common in conditions unrelated to prostate cancer; therefore, we maintained these entities in the table.
The following PTs (all reports) within the specified SOC had an EB05 of 2.0 or higher but were not included in the table owing to nonspecific terminology. General disorders and administration site conditions: ill-defined disorder (n = 137), adverse reaction (n = 11); investigations: investigation (n = 8).
Indicates whether the adverse event (represented by the specified PT) is a labeled event or consistent with a labeled event. The product label instructs patients to report catheter-associated symptoms (eg, swelling, redness) to a health care professional; therefore, we considered all device- or catheter-associated events as labeled events, including hematoma.
Although the EB05 was lower than 2.0, reports of myocardial infarction (n = 38) were reviewed owing to the inclusion of cardiovascular disorders in the “Warnings and Precautions” section of the product label (EBGM [serious reports], 0.53; 90% CI, 0.40-0.68).
Not a labeled event with respect to peripheral blood; labeled event with respect to characterization of product.
Although EB05 was lower than 2.0, reports of stroke were reviewed owing to the inclusion of cerebrovascular disease in the “Warnings and Precautions” section of the product label. Data for all serious reports were as follows: ischemic stroke (n = 6; EBGM, 1.7; 90% CI, 0.9-3.0); hemorrhagic stroke (n = 5; EBGM, 1.3; 90% CI, 0.7-2.3); embolic stroke (n = 6; EBGM, 2.9; 90% CI, 1.5-5.0). All reports were serious.