Adverse reactions
The following adverse reactions are discussed elsewhere in labeling:
- Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] .
- Neurologic Toxicity, Including ICANS [see Warnings and Precautions (5.2) ] .
- Infections [see Warnings and Precautions (5.4) ] .
- Neutropenia [see Warnings and Precautions (5.5) ] .
- Hepatotoxicity [see Warnings and Precautions (5.6) ] . Most common adverse reactions (incidence ≥20%) are CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed/Refractory Multiple Myeloma MagnetisMM-3 The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14) ]. The safety population described (n = 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8.
Among patients who received ELREXFIO, 42% were exposed for 6 months or longer and 9% were exposed for one year or longer. The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American. Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule.
Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%).
Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%). Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.
The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. Table 8 summarizes adverse reactions in MagnetisMM-3.
Table 8. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria. System Organ Class Preferred Term ELREXFIO N = 183 All Grades (%) Grade 3 or 4 (%) Immune system disorders Cytokine release syndrome 58
0.5 Only grade 3 adverse reactions occurred. Hypogammaglobulinemia Includes other related terms. 13
2.2 General disorders and site administration conditions Fatigue 43 6 Injection site reaction 37 0 Pyrexia 21
1.1 Gastrointestinal disorders Diarrhea 36
1.1Nausea 21 0 Constipation 14 0 Vomiting 14 0 Infections
Upper respiratory tract infection 36
4.9Pneumonia
Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. 32 19 Sepsis Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. 15 11 Urinary tract infection 12
4.4Musculoskeletal
and connective tissue disorders Musculoskeletal pain 34
2.7Metabolism
and nutrition disorders Decreased appetite 26
1.1Skin and Subcutaneous
Tissue disorders Rash Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. 26 0 Dry skin 14 0 Skin exfoliation 10 0 Respiratory, thoracic and mediastinal disorders Cough 24 0 Dyspnea 15
3.3 Nervous system disorders Headache 18 0 Encephalopathy Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. 14
2.2 Sensory neuropathy Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. 13
0.5 Motor dysfunction Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. 14
1.1 Cardiac disorders Cardiac arrhythmia 16
1.6 Vascular disorders Hemorrhage 13
1.6 Psychiatric disorders Insomnia 13 0 Injury, poisoning and procedural complications Fall 10
0.5 Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barré syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy. Table 9 summarizes laboratory abnormalities in MagnetisMM-3. Table 9. Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Laboratory tests were graded according to NCI-CTCAE Version 5.0.
Laboratory Abnormality ELREXFIO The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocyte count decreased 91 84 White blood cell decreased 69 40 Hemoglobin decreased 68 43 Neutrophil count decreased 62 51 Platelet count decreased 61 32 Chemistry Albumin decreased 55 6 AST increase 40 6 Creatinine increased 38
3.3 Potassium decreased 36 8 ALT increase 36
3.8 Alkaline phosphatase increased 34
1.1 Creatinine clearance decreased 32 10
