Age: 75.0
Sex: M
Vaccine: VARZOS
Symptoms: Insomnia, Lymphocyte count normal, Lymphocyte percentage decreased, Malignant melanoma, Mean cell haemoglobin concentration normal
Clinical narrative: This solicited report was received from a currently 76-year-old male patient enrolled in a Patient Support Program who was reporting on himself. The patient's concurrent conditions included hypertension and high cholesterol, there was no history of drug reactions or allergies reported. The patient's concomitant medications included LIPITOR, BYSTOLIC and unspecified vitamins. On an unknown date in December 2016, he was diagnosed with melanoma located in his right sacrum around nerves which was causing pain. On 30-DEC-2016, the patient started therapy with KEYTRUDA every three weeks, intravenously (dose, lot number and expiration date were not reported) for melanoma. The patient stated that the pain was no worse or different since starting KEYTRUDA. On an unknown date (reported as sometime after starting KEYTRUDA), the patient experienced a lack of energy. He did not receive any treatment for the event and did not seek medical attention. A product quality complaint was not involved. At the time of the report, the patient continued the therapy with KEYTRUDA, and the outcome of lack of energy was not reported. The causal relationship between the event and KEYTRUDA was not reported. Follow-up information was received from the patient on 15-MAR-2017. The patient stated that the previously reported pain around the right sacrum area had improved since 21-FEB-2017. He additionally reported recurrent muscle pain in his left arm near the biceps muscle which began on approximately 01-MAR-2017 (reported as approximately 2 weeks ago). He stated that the pain primarily occurred when he lifted his arm. He treated the pain with ALEVE and ADVIL and he reported both medications helped the pain very little. The patient remained on KEYTRUDA. The outcome of muscle pain was not reported. The relatedness between the event and the therapy with KEYTRUDA was not provided. Follow up information was received from the patient on 05-APR-2017. On 20-MAR-2017, the patient had a Positron Emission Tomography (PET) scan performed, which showed, according to him, that KEYTRUDA "was working". He also stated that during the PET scan, the technician tied his arms down and this created more pain near the shoulder areas than usual. On 21-MAR-2017 at 06:30, the patient experienced a seizure while sleeping in bed. His wife called an ambulance and he was admitted to the hospital on the same day, where he stayed overnight. During the hospitalization, a Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), a brain scan and electroencephalogram (EEG) were performed and were all normal. The patient stated that a stroke was also ruled out. On 31-MAR-2017, the patient received his fifth infusion of KEYTRUDA, which was delayed by 7 days. The patient reported, he would be wearing an ambulatory EEG from 07-APR-2017 to 09-APR-2017. He also stated that the previously reported symptom of pain in the left arm continued and at the time of reporting he experienced pain in both arms, however the pain in the left arm was worse. The patient felt that the pain was near the shoulders and he thought it might be joint pain. The patient was treated for pain with ALEVE, which provided little relief. The outcome of seizure was not reported. The therapy with KEYTRUDA was continued at the time of this report. The relatedness between seizure and joint pain and KEYTRUDA was not reported. Upon internal review, the event of seizure was considered to be medically significant. Follow-up information has been received via a phone call from the registered nurse and the patient on 25-APR-2017. The registered nurse stated that the patient was receiving 160 mg of KEYTRUDA every three weeks. She also stated that in March 2017 (reported as during the patient's hospitalization for the seizures), the therapy with LIPITOR was discontinued as the physician did not know what caused the seizures. Therefore, the therapy with LIPITOR (start date, dose, frequency, route of administration were not reported) has been changed from concomitant therapy to suspect therapy. The patient also confirmed that the previously reported EEG results were normal and that he remained on the therapy with KEYTRUDA. The relatedness between the events and LIPITOR was not provided. Follow up information has been received from the physician via medical records on 28-APR-2017. The patient was a married male, who was living with a spouse. He was a former smoker and denied any illicit drug use. It was confirmed that the patient had a hypertension and hypercholesterolemia. The patient's current conditions included also an allergy to meloxicam, multiple skin cancers (including squamous cell, basal cell and melanoma) and his past surgical history included multiple skin surgeries. The patient's primary diagnosis was malignant melanoma of other part of trunk. An unspecified work up performed on an unknown date, showed that he had spinal lesion. A CT scan guided biopsy was performed in the hospital and it showed that he had metastatic melanoma. The patient's concomitant medications included also CENTRUM SILVER, ubidecarenone, hydrochlorothiazide, KLOR-CON, resveratrol, ascorbic acid, vitamin E, prochlorperazine maleate, lorazepam, lidocaine hydrochloride (manufacturer unknown), and LIDODERM and drug reported as "Super B Maxi Complex 0.4 mg tablet". On 23-DEC-2016, the PET/CT scan showed lung mass in addition to the spine metastasis. It was discussed with the patient and it was decided that he would start a treatment with KEYTRUDA next week. On 06-JAN-2017, the patient denied any complaint. It was reported that the patient started the first dose of KEYTRUDA that day, however it was also reported that he started KEYTRUDA on 30-DEC-2016. On 13-JAN-2017, the patient denied any new complaint and he was doing fine. It was reported that "he got the first dose of control of the KEYTRUDA". On an unknown date in January 2017, the patient complained of back pain. On 20-JAN-2017, the patient was still complaining of back pain and he continued with LIDODERM 5% topical patch. In addition to that he had insomnia (onset date was not reported) he continued with lorazepam 0.5 mg tablet. On 21-JAN-2017, the patient experienced muscle aches (previously reported as 01-MAR-2017). On 08-FEB-2017, the patient was taking immunotherapy. He was doing fine with no complication. It was decided that he would continue current treatment. On 01-MAR-2017, the patient was doing fine and was taking immunotherapy. It was reported that his disease would be reevaluated after this cycle. On 29-MAR-2017, the patient experienced one episode of partial seizure (previously reported as 21-MAR-2017). On 29-MAR-2017, the PET/CT scan showed improvement. It was decided that he would continue current treatment since he had excellent response. On 19-APR-2017, patient was doing fine in immunotherapy. He denied any new complaint and was still complaining of muscle aches. On the same day, the patient had tests performed (reported as "vitals"), which included: height (68 inches), weight (172 lb), temperature (98.0 F), pulse (74 (unit not provided)), systolic blood pressure (BP) (152 (unit not provided)), diastolic BP (88 (unit not provided)), oxygen (O2) saturation (98%). On the same day, the patient had also laboratory tests performed, which included: white blood cell count (WBC)=7.7x1000/micro-l, red blood cell count (RBC)=4.40x1000000/micro-l, haematocrit (HCT)=39.2%, haemoglobin (HGB)=13.4 g/dL, mean cell volume (MCV)=89 fL, mean cell haemoglobin concentration (MCHC)=34.2 g/dL, red cell distribution width (RDW)=11.6%, platelet=313x1000/micro-l, mean platelet volume (MPV)=6.3 fL, neutrophil percentage (Neut%)=62.0%, lymphocyte count (Lymph#)=1.35x1000/micro-l, basophil count (BASO#)=0.05x1000/micro-l, eosinophil count (EOS#)=0.43x1000/micro-l, lymphocyte percentage (Lymph%)=17.7%, basophil percentage (BASO%)=0.7%, eosinophil percentage (EOS%)=5.6%, sodium=132 mmol/L, potassium=5.0 mmol/L, chloride=94 mmol/L, carbon dioxide (CO2)=23 mmol/L, glucose=79 mg/dL, blood urea nitrogen (BUN)=10 mg/dL, creatinine=0.70 mg/dL, calcium=9.0 mg/dL, total protein=6.6 g/dL, albumin=4.2 g/dl, albumin/globulin (A/G) ratio=1.8, globulin=2.4 g/dL, total bilirubin=0.4 mg/dL, alkaline phosphatase=63 IU/l, aspartate aminotransferase (AST)=27 IU/l, alanine aminotransferase (ALT)=20 IU/l, BUN/creatinine ratio=14, mean cell haemoglobin (MCH)=30.4 pg, mixed cell count (MXD#)=1.07x10^3/micro-l, mixed cell percentage (MXD%)=14.0%, neutrophil count (NEUT#)=4.74x1000/micro-l. On an unknown date, the patient had review of systems performed with following results: constitutional - no weight loss, no fatigue, no loss of appetite, no night sweats, no fever, no chills, pain assessment discomforting - moderate pain, experiencing pain in back (pain description: a pain that did not change in its intensity); eyes - no blurred vision, no double vision, no difficulty seeing, Ears, nose, mouth and throat - no hearing loss, no ringing in ears, no sinus trouble, no difficulty swallowing, no sore throat, no nasal drainage, no nose bleeds, no hoarseness, no chest pain, no heart palpitations, no light headedness, no swelling in legs, no episodes of passing out, respiratory - no cough, no sputum production, no hemoptysis, no shortness of breath, no orthopnea, no paroxysmal nocturnal dyspnea; gastrointestinal - no nausea, no vomiting, no heartburn, no constipation, no diarrhea, no abdominal pain, no rectal bleeding, no bowel incontinence; musculoskeletal - no muscle pain, no muscle stiffness, no joint pain, patient denied any joint swelling, no back pain; skin - no skin rash; neurological - no headache, no seizures, no dizziness, no loss of balance, no weakness of limbs, no loss of sensation, no tingling, no memory loss, no difficulty thinking clearly; psychiatric - no nervousness, no depression, no restlessness, no difficulty sleeping; hematologic/lymphatic/immunologic - no bruising, no bleeding, no lumps in arm-pits, no lumps in neck, no lumps in groin. On an unknown date, the patient had also physical examination with following results: general - well developed, well nourished, in no acute distress, appeared stated age, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (light house work, office work), Oncology Group (OG) performance: 1; head - atraumatic and normocephalic; eyes - pupils equal, round and reactive to light and accommodation (PERRLA), extra ocular movement intact (EOMI), no jaundice or pallor, there was no redness/drainage in conjunctiva; ears, nose, throat and neck - trachea was midline, no JVD, no lymphadenopathy present, thyroid was midline and not enlarged, neck was supple, no oral lesions noted; cardiovascular - S1, S2 without murmurs, no S3/S4 gallop, no rubs or clicks noted, no carotid artery bruits, heart beat regular, no parasternal heave, radial pulses were present; femoral pulses were present, pedal pulses were present; chest - chest symmetrical; no kyphosis, no scoliosis noted; respiratory - lungs clear to auscultation, no rales or rhonchi, no added sounds, percussion and palpation were normal; gastrointestinal - abdomen was soft, non-tender, non-distended, without masses, no ascites present, no hepatosplenomegaly palpated, no hernia present; bowel sounds present in all 4 quadrants; hematologic/lymphatic - no petechiae, no purpura, no neck lymphadenopathy, no axillary lymphadenopathy, no groin lymphadenopathy; musculoskeletal - normal gait and station, normal range of motion, strength and tone were normal; extremities - no edema, no cyanosis, no digital clubbing, no discoloration; skin physical examination - no abnormal skin lesions noted; neurologic - patient was alert and oriented X3, no hemiplegia, no hemiparesis, cranial nerves intact, there were no sensory deficits, no motor deficits present; rectal - no rectal/anal masses present; genitourinary - no genitourinary abnormalities noted. On an unknown date, the PET/CT scan showed that disease status is stable. Therapy with KEYTRUDA was continued at the time of this report and it was planned to administer it on an unknown date "next week". The plan was to order BRAF testing, renew lorazepam and LIDODERM and obtain patient's old records. The diagnosis and care plan were discussed with the patient in detail. The goal of treatment was to palliate the disease and disease related symptoms, improve quality of life and hopefully prolong patient's life. The outcome of back pain was reported as not changing in its intensity (not recovered) and the outcome of insomnia was not reported. The relatedness between the back pain and insomnia and therapy with KEYTRUDA and LIPITOR was not reported. All available medical records will be provided upon request. Follow up information has been received from the physician on 16-MAY-2017. The frequency of KEYTRUDA administration was updated to every 2 weeks. On 23-DEC-2016 (previously reported as January 2017), the patient experienced back pain. It was confirmed that the patient was still complaining of back pain. The treatment with KEYTRUDA was continuing but it was also reported that dechallenge with back pain was negative. Follow up information has been received from the patient on 01-JUN-2017. The patient stated that since starting KEYTRUDA, the pain caused by melanoma that was located in his right sacrum around nerves improved. On an unknown date (reported as 3-4 years ago), the patient received an unspecified shingles vaccine (manufacturer unknown). Then approximately on 18-MAY-2017 (reported as 2 weeks ago), he was diagnosed with shingles. He was prescribed an unspecified medication which he took for 5 days and then saw his physician for a follow-up appointment. The physician then prescribed the same unspecified medication for another 7 days. The patient stated at that time the shingles was 80-90% resolved and he felt it was a mild case (reported as "cause") of shingles. Therapy with KEYTRUDA was continued. Causality between the event of shingles and unexpected therapeutic benefit was not provided. The events of cancer pain, metastatic malignant melanoma, squamous cell carcinoma of skin, basal cell carcinoma, multiple skin surgeries, pulmonary mass and metastases to spine, previously reported as concurrent conditions, were considered to be adverse events. Causality between these events and KEYTRUDA was not related. Causality between these events and unspecified shingles vaccine (manufacturer unknown) was unknown. Upon internal review, the events of cancer pain, metastatic malignant melanoma, squamous cell carcinoma of skin, basal cell carcinoma and metastases to spine were determined to be medically significant. Follow up information has been received from the patient on 13-JUL-2017. The patient received ten radiation treatments to treat his right sacrum sometime in June 2017. The radiation treatment was to help with sacrum pain. It was reported that following radiation treatment, his pain improved. No further information was provided. Additional information has been requested. Company Causality Assessment: Based on the clinically relevant information currently available for this individual case, the reported event, seizure, is considered unlikely related to the therapy. The evidence is not sufficient to suggest a relationship between the therapy and the reported serious adverse event. Causality assessment for seizures is impacted by the confounding factor, of concomitant use of LIPITOR reported in the narrative and which was discontinued by the investigator. Regarding the events malignant neoplasm progression, cancer pain, metastases to spine, the natural progression of the underlying metastatic malignancy constitutes a more plausible alternative explanation for these events. Regarding the event of squamous cell carcinoma of skin and basal cell carcinoma, these events are known to occur at a background rate in elderly Caucasian population, in addition to patient's medical history of other skin cancer, which further explains the apparition of the new skin cancer events. The other events included in this report were considered as nonserious. Company Comment- No changes to the product safety information are warranted at this time. Merck and Co., Inc., known as MSD outside of the two countries, continues to monitor the safety profile of KEYTRUDA.