ABECMA® Safety Profile After a One-time Infusion1*†
Most common adverse reactions
- The most common nonlaboratory adverse reactions (incidence ≥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 (≥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%
- The most common (≥10%) grade 3 or 4 nonlaboratory adverse reactions were febrile neutropenia (16%) and infections—pathogen unspecified (15%)
Summary of adverse reactions observed in at least 10% of patients treated with ABECMA in the KarMMa study
Any Grade, % | Grade 3 or Higher, % | |
---|---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) | |
Blood and lymphatic system disorders | ||
Febrile neutropenia | 16 | 16 |
Cardiac disorders | ||
Tachycardia‡ | 19 | 0 |
Gastrointestinal disorders | ||
Diarrhea | 35 | 1.6 |
Nausea | 29 | 0 |
Constipation | 16 | 0 |
Vomiting | 15 | 0 |
Oral pain§ | 12 | 0 |
General disorders and administration site conditions | ||
Fatigue‖ | 45 | 3.1 |
Pyrexia | 25 | 1.6 |
General physical health deterioration | 11 | 10 |
Edema¶ | 25 | 0 |
Chills | 11 | 0 |
Immune system disorders | ||
Cytokine release syndrome | 85 | 9 |
Hypogammaglobulinemia# | 41 | 0.8 |
Infections and infestations** | ||
Infections – Pathogen unspecified | 51 | 15 |
Viral infections | 27 | 9 |
Bacterial infections | 15 | 3.9 |
Pneumonia†† | 17 | 9 |
Upper respiratory tract infection‡‡ | 34 | 1.6 |
Investigations | ||
Weight decreased | 13 | 1.6 |
Metabolism and nutrition disorders | ||
Decreased appetite§§ | 22 | 0.8 |
Musculoskeletal and connective tissue disorders | ||
Musculoskeletal pain‖‖ | 45 | 3.1 |
Motor dysfunction¶¶ | 11 | 0 |
Nervous system disorders | ||
Encephalopathy## | 26 | 6 |
Headache*** | 23 | 0 |
Dizziness††† | 17 | 0.8 |
Neuropathy peripheral‡‡‡ | 17 | 0.8 |
Tremor§§§ | 10 | 0 |
Psychiatric disorders | ||
Insomnia‖‖‖ | 13 | 0 |
Anxiety¶¶¶ | 12 | 0.8 |
Renal and urinary disorders | ||
Renal failure### | 10 | 2.4 |
Respiratory, thoracic, and mediastinal disorders | ||
Cough**** | 23 | 0 |
Dyspnea†††† | 13 | 2.4 |
Skin and subcautaneous tissue disorders | ||
Rash‡‡‡‡ | 14 | 0.8 |
Xerosis§§§§ | 11 | 0 |
Vascular disorders | ||
Hypotension‖‖‖‖ | 17 | 0 |
Hypertension | 11 | 3.1 |
Blood and lymphatic system disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Febrile neutropenia | |
16 | 16 |
Cardiac disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Tachycardia‡ | |
19 | 0 |
Gastrointestinal disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Diarrhea | |
35 | 1.6 |
Nausea | |
29 | 0 |
Constipation | |
16 | 0 |
Vomiting | |
15 | 0 |
Oral pain§ | |
12 | 0 |
General disorders and administration site conditions
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Fatigue‖ | |
45 | 3.1 |
Pyrexia | |
25 | 1.6 |
General physical health deterioration | |
11 | 10 |
Edema¶ | |
25 | 0 |
Chills | |
11 | 0 |
Immune system disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Cytokine release syndrome | |
85 | 9 |
Hypogammaglobulinemia# | |
41 | 0.8 |
Infections and infestations**
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Infections – Pathogen unspecified | |
51 | 15 |
Viral infections | |
27 | 9 |
Bacterial infections | |
15 | 3.9 |
Pneumonia†† | |
17 | 9 |
Upper respiratory tract infection‡‡ | |
34 | 1.6 |
Investigations
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Weight decreased | |
13 | 1.6 |
Metabolism and nutrition disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Decreased appetite§§ | |
22 | 0.8 |
Musculoskeletal and connective tissue disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Musculoskeletal pain‖‖ | |
45 | 3.1 |
Motor dysfunction¶¶ | |
11 | 0 |
Nervous system disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Encephalopathy## | |
26 | 6 |
Headache*** | |
23 | 0 |
Dizziness††† | |
17 | 0.8 |
Neuropathy peripheral‡‡‡ | |
17 | 0.8 |
Tremor§§§ | |
10 | 0 |
Psychiatric disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Insomnia‖‖‖ | |
13 | 0 |
Anxiety¶¶¶ | |
12 | 0.8 |
Renal and urinary disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Renal failure### | |
10 | 2.4 |
Respiratory, thoracic, and mediastinal disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Cough**** | |
23 | 0 |
Dyspnea†††† | |
13 | 2.4 |
Skin and subcautaneous tissue disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Rash‡‡‡‡ | |
14 | 0.8 |
Xerosis§§§§ | |
11 | 0 |
Vascular disorders
Any Grade, % | Grade 3 or Higher, % |
---|---|
150-450 × 106 (N=127) | 150-450 × 106 (N=127) |
Hypotension‖‖‖‖ | |
17 | 0 |
Hypertension | |
11 | 3.1 |
*Treatment process includes leukapheresis, drug manufacturing, administration, and adverse event monitoring. A single dose of ABECMA contains a cell suspension of 300 to 460 106 CAR-positive T cells in one or more infusion bags.
†Data at primary analysis. Safety profile remained consistent with longer follow-up and no new safety signals were observed.
‡Tachycardia includes sinus tachycardia, tachycardia.
§Oral pain includes oral pain, oropharyngeal pain, toothache.
‖Fatigue includes asthenia, fatigue, malaise.
¶Edema includes edema, face edema, fluid overload, fluid retention, generalized edema, peripheral edema, peripheral swelling, scrotal swelling, swelling.
#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%).
**Infections and infestations System Organ Class Adverse Events are grouped by pathogen type and selected clinical syndromes.
††Pneumonia includes bronchopulmonary aspergillosis, lung infection, pneumonia, pneumonia aspiration, pneumonia cytomegaloviral, pneumonia pneumococcal, pneumonia pseudomonal. Pneumonias may also be included under pathogen categories.
‡‡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.
§§Decreased appetite includes decreased appetite, hypophagia.
‖‖Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, spinal pain.
¶¶Motor dysfunction includes dysphonia, eyelid ptosis, hypotonia, motor dysfunction, muscle spasms, muscular weakness, restless legs syndrome.
##Encephalopathy 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.
***Headache includes headache, head discomfort, sinus headache.
†††Dizziness includes dizziness, presyncope, syncope, vertigo.
‡‡‡Neuropathy peripheral includes carpal tunnel syndrome, hypoesthesia, hypoesthesia oral, neuralgia, neuropathy peripheral, paresthesia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, sciatica.
§§§Tremor includes asterixis, tremor.
‖‖‖Insomnia includes insomnia, sleep deficit, sleep disorder.
¶¶¶Anxiety includes anxiety, feeling jittery, nervousness.
###Renal failure includes acute kidney injury, blood creatinine increased, chronic kidney disease, renal failure, renal impairment.
****Cough includes cough, productive cough, upper-airway cough syndrome.
††††Dyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure.
‡‡‡‡Rash includes acne, dermatitis, dermatitis bullous, erythema, rash, rash macular, rash papular, urticaria.
§§§§Xerosis includes dry eye, dry mouth, dry skin, lip dry, xerosis.
‖‖‖‖Hypotension includes hypotension, orthostatic hypotension.
Grade 3 or 4 laboratory abnormalities worsening from baseline in at least 10% of patients treated with ABECMA in the KarMMa study
150-450 × 106 (N=127) % | |
---|---|
Neutropenia | 96 |
Leukopenia | 96 |
Lymphopenia | 92 |
Thrombocytopenia | 63 |
Anemia | 63 |
Hypophosphatemia | 45 |
Hyponatremia | 10 |
aPTT increased (seconds) | 10 |
aPTT=activated partial thromboplastin time; ARs=adverse reactions; CRS=cytokine release syndrome; 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 × 106 column.