ABECMA SIDE EFFECTS
- Generic Name: idecabtagene vicleucel suspension
- Brand Name: Abecma
- Drug Class: CAR-T Cell Therapies
SIDE EFFECTS
The following adverse reactions are described elsewhere in the labeling:
- Cytokine Release Syndrome.
- Neurologic Toxicities.
- Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS).
- Hypersensitivity Reactions.
- Infections.
- Prolonged Cytopenias.
- Hypogammaglobulinemia.
Clinical 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 clinical practice.
The safety data described in this section reflect the exposure to ABECMA in the KarMMa study, in which 127 patients with relapsed/refractory multiple myeloma received ABECMA across a dose range of 150 to 518 x 106 CAR-positive T cells. Patients with a history of CNS disease (such as seizure or cerebrovascular ischemia) or requiring ongoing treatment with chronic immunosuppression were excluded. The median duration of follow-up was 11.4 months. The median age of the study population was 61 years (range: 33 to 78 years); 35% were 65 years or older, and 60% were men. The Eastern Cooperative Oncology Group (ECOG) performance status at baseline was 0 in 45%, 1 in 53%, and 2 in 2% of patients. Seven percent of the patients treated with ABECMA had creatinine clearance <45 ml/min.
The most common (greater than or equal to 10%) Grade 3 or 4 nonlaboratory adverse reactions were febrile neutropenia (16%) and infections – pathogen unspecified (15%).
The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) included CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.
Serious adverse reactions occurred in 67% of patients. The most common nonlaboratory (greater than or equal to 5%) serious adverse reactions included CRS (18%), general physical health deterioration (10%), pneumonia (12%), infections-pathogen unspecified (19%), viral infections (9%), sepsis (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 6%.
Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with ABECMA. Table 4 describes the most common Grade 3 or 4 laboratory abnormalities.
Table 3: Adverse Reactions Observed in at Least 10% of Patients Treated with ABECMA in the KarMMa Study
| System Organ Class Preferred Term |
Target Dose of ABECMA (CAR-Positive T Cells) | |
| Any Grade | Grade 3 or Higher | |
| [150 to 450 x 106] (N=127) % |
[150 to 450 x 106] (N=127) % |
|
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 16 | 16 |
| Cardiac disorders | ||
| Tachycardiaa | 19 | 0 |
| Gastrointestinal disorders | ||
| Diarrhea | 35 | 1.6 |
| Nausea | 29 | 0 |
| Constipation | 16 | 0 |
| Vomiting | 15 | 0 |
| Oral painb | 12 | 0 |
| General disorders and administration site conditions | ||
| Fatiguec | 45 | 3.1 |
| Pyrexia | 25 | 1.6 |
| General physical health deterioration | 11 | 10 |
| Edemad | 25 | 0 |
| Chills | 11 | 0 |
| Immune system disorders | ||
| Cytokine release syndrome | 85 | 9 |
| Hypogammaglobulinemiae | 41 | 0.8 |
| Infections and infestationsf | ||
| Infections – Pathogen unspecified | 51 | 15 |
| Viral infections | 27 | 9 |
| Bacterial infections | 15 | 3.9 |
| Pneumoniag | 17 | 9 |
| Upper respiratory tract infectionh | 34 | 1.6 |
| Investigations | ||
| Weight decreased | 13 | 1.6 |
| Metabolism and nutrition disorders | ||
| Decreased appetitei | 22 | 0.8 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal painj | 45 | 3.1 |
| Motor dysfunctionk | 11 | 0 |
| Nervous system disorders | ||
| Encephalopathyl | 26 | 6 |
| Headachem | 23 | 0 |
| Dizzinessn | 17 | 0.8 |
| Neuropathy peripheralo | 17 | 0.8 |
| Tremorp | 10 | 0 |
| Psychiatric disorders | ||
| Insomniaq | 13 | 0 |
| Anxietyr | 12 | 0.8 |
| Renal and urinary disorders | ||
| Renal failures | 10 | 2.4 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Cought | 23 | 0 |
| Dyspneau | 13 | 2.4 |
| Skin and subcutaneous tissue disorder | ||
| Rashv | 14 | 0.8 |
| Xerosisw | 11 | 0 |
| Vascular disorders | ||
| Hypotensionx | 17 | 0 |
| Hypertension | 11 | 3.1 |
| CAR=chimeric antigen receptor. a Tachycardia includes sinus tachycardia, tachycardia. b Oral pain includes oral pain, oropharyngeal pain, toothache. c Fatigue includes asthenia, fatigue, malaise. d Edema includes edema, face edema, fluid overload, fluid retention, generalized edema, peripheral edema, peripheral swelling, scrotal swelling, swelling. e Hypogammaglobulinemia includes patients with adverse events (21%) of blood immunoglobulin G decreased, hypogammaglobulinemia, hypoglobulinemia; and/or patients with laboratory IgG levels below 500 mg/dL following ABECMA infusion (25%). f Infections and infestations System Organ Class Adverse Events are grouped by pathogen type and selected clinical syndromes. g Pneumonia includes bronchopulmonary aspergillosis, lung infection, pneumonia, pneumonia aspiration, pneumonia cytomegaloviral, pneumonia pneumococcal, pneumonia pseudomonal. Pneumonias may also be included under pathogen categories. h Upper respiratory tract infection includes laryngitis, nasopharyngitis, pharyngeal erythema, pharyngitis, respiratory tract congestion, respiratory tract infection, rhinitis, rhinovirus infection, sinusitis, upper respiratory tract infection, upper respiratory tract infection bacterial. Upper respiratory tract infections may also be included under pathogen categories. i Decreased appetite includes decreased appetite, hypophagia. j Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, spinal pain. k Motor dysfunction includes dysphonia, eyelid ptosis, hypotonia, motor dysfunction, muscle spasms, muscular weakness, restless legs syndrome. lEncephalopathy includes amnesia, bradyphrenia, cognitive disorder, confusional state, depressed level of consciousness,disturbance in attention, dyscalculia, dysgraphia, encephalopathy, lethargy, memory impairment, mental status changes,metabolic encephalopathy, somnolence, toxic encephalopathy. m Headache includes headache, head discomfort, sinus headache. n Dizziness includes dizziness, presyncope, syncope, vertigo. oNeuropathy peripheral includes carpal tunnel syndrome, hypoesthesia, hypoesthesia oral, neuralgia, neuropathyperipheral, paresthesia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, sciatica. p Tremor includes asterixis, tremor. q Insomnia includes insomnia, sleep deficit, sleep disorder. r Anxiety includes anxiety, feeling jittery, nervousness. s Renal failure includes acute kidney injury, blood creatinine increased, chronic kidney disease, renal failure, renal impairment. t Cough includes cough, productive cough, upper-airway cough syndrome. uDyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure. v Rash includes acne, dermatitis, dermatitis bullous, erythema, rash, rash macular, rash papular, urticaria. w Xerosis includes dry eye, dry mouth, dry skin, lip dry, xerosis. x Hypotension includes hypotension, orthostatic hypotension. |
||
Other clinically important adverse reactions that occurred in less than 10% of patients treated with ABECMA include the following:
- Blood and lymphatic system disorders: coagulopathya (9%)
- Cardiac disorders: atrial fibrillation (4.7%), cardiomyopathyb (1.6%)
- Gastrointestinal disorders: gastrointestinal hemorrhagec (3.1%)
- Immune system disorders: hemophagocytic lymphohistiocytosis (3.1%)
- Infections and infestations: fungal infections (8%), sepsisd (9%)
- Nervous system disorders: aphasiae (7%), ataxiaf (3.1%), paresisg (2.4%), seizure (1.6%)
- Psychiatric disorders: deliriumh (6%)
- Respiratory, thoracic, and mediastinal disorders: hypoxia (2.4%), pulmonary edema (2.4%)
- Vascular disorders: thrombosisi (3.1%)
a Coagulopathy includes activated partial thromboplastin time prolonged, anticoagulation drug level above therapeutic, disseminated intravascular coagulation, international normalized ratio increased.
b Cardiomyopathy includes stress cardiomyopathy, ventricular hypertrophy.
c Gastrointestinal hemorrhage includes gastrointestinal hemorrhage, hemorrhoidal hemorrhage, melena.
d Sepsis includes bacteremia, enterococcal bacteremia, Escherichia bacteremia, sepsis, septic shock, Serratia bacteremia, streptococcal bacteremia.
e Aphasia includes aphasia, dysarthria.
f Ataxia includes ataxia, gait disturbance, Romberg test positive.
g Paresis includes cranial nerve disorder, hemiparesis.
h Delirium includes delirium, disorientation, hallucination.
i Thrombosis includes deep vein thrombosis, jugular vein thrombosis, portal vein thrombosis, pulmonary embolism.
Laboratory Abnormalities
Table 4 presents the most common Grade 3 or 4 laboratory abnormalities, based on laboratory data, occurring in at least 10% of patients.
Table 4: Grade 3 or 4a Laboratory Abnormalities Worsening from Baseline in at Least 10% of Patients Treated with ABECMA in the KarMMa Study
| Laboratory Abnormality | Dose=[150 to 450 x 106 CAR-Positive T cells] (N=127) % |
| Grade 3 or 4 (%) | |
| Neutropenia | 96 |
| Leukopenia | 96 |
| Lymphopenia | 92 |
| Thrombocytopenia | 63 |
| Anemia | 63 |
| Hypophosphatemia | 45 |
| Hyponatremia | 10 |
| aPTT Increased (seconds) | 10 |
| aNCI CTCAE=Common Terminology Criteria for Adverse Events version 4.03. aPTT=activated partial thromboplastin time; CAR=chimeric antigen receptor; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute. Laboratory tests were graded according to NCI CTCAE Version 4.03. Laboratory abnormalities are sorted by decreasing frequency in the 150 to 450 x 106 column. |
|
Other clinically important Grade 3 or 4 laboratory abnormalities (based on laboratory data) that occurred in less than 10% of patients treated with ABECMA include the following: alanine aminotransferase increased, aspartate aminotransferase increased, hypoalbuminemia, alkaline phosphatase increased, hyperglycemia, hypokalemia, bilirubin increased, hypofibrinogenemia, and hypocalcemia.
Immunogenicity
ABECMA has the potential to induce anti-product antibodies. In clinical studies, humoral immunogenicity of ABECMA was measured by determination of anti-CAR antibody in serum pre- and post-administration. In the KarMMa study, 3% of patients (4/127) tested positive for pre-infusion anti-CAR antibodies and treatment-induced anti-CAR antibodies were detected in 47% (60/127) of the patients. There is no evidence that the presence of pre-existing or post-infusion anti-CAR antibodies impact the cellular expansion, safety, or effectiveness of ABECMA. 21
DRUG INTERACTIONS
Drug/Laboratory Test Interactions
HIV and the lentivirus used to make ABECMA have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received ABECMA.
SRC: NLM .