The safety data described in this section reflect exposure to CARVYKTI® in 285 patients with relapsed or refractory multiple myeloma: one randomized, open label with 188 patients in CARTITUDE-4 and one single-arm, open label study with 97 patients in CARTITUDE-1. Because clinical trials are conducted under widely varying conditions, adverse reactions observed in clinical trials may not reflect the rates observed in practice.
Boxed Warning
BOXED WARNING
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES
- Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI®. Do not administer CARVYKTI® to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
- Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed.
- Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI®.
- Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI®. HLH/MAS can occur with CRS or neurologic toxicities.
- Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI®.
- Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI®. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®.
- CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS Program.
CARVYKTI® REMS PROGRAM
CARVYKTI® is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called CARVYKTI® REMS. The FDA has determined that a REMS is necessary to ensure that the benefits of CARVYKTI® outweigh the risks of cytokine release syndrome and neurological toxicities. One of the goals of the CARVYKTI® REMS is to ensure that healthcare professionals that prescribe, dispense, or administer CARVYKTI® at the CARVYKTI® Certified Treatment Centers are aware of how to manage the risks of CRS and neurological toxicities.
For more information, visit www.CARVYKTIrems.com
CYTOKINE RELEASE SYNDROME (CRS)
In CARTITUDE-4 and CARTITUDE-1 (N=285)1
CRS, including fatal or life-threatening reactions, occurred after CARVYKTI® infusion
| Any grade | GRADE ≥3 (2019 ASTCT Grade) |
|---|---|
| 84%(n=238/285) | 4%(n=11/285) |
MEDIAN TIME TO ONSET
7 DAYS
(range, 1-23 days)
MEDIAN DURATION
4 DAYS
(range, 1-97 days)
- Cytokine release syndrome resolved in 82% with a median duration of 4 days (range, 1-97 days)
- The most common manifestations of CRS in all patients combined (≥ 10%) included fever (84%), hypotension (29%), and aspartate aminotransferase increased (11%)
- Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia
- Identify CRS based on clinical presentation*
- Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS
- Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS
*See CARVYKTI® USPI Table 1 CRS grading and management guidance.
In CARTITUDE-4 (N=188)
| Any grade | GRADE 3-4 |
|---|---|
| 78% | 3% |
In CARTITUDE-1 (N=97)
| Any grade | GRADE 3-4 |
|---|---|
| 95% | 4% |
ASTCT=American Society of Transplantation and Cellular Therapy; HLH=hemophagocytic lymphohistiocytosis; MAS=macrophage activation syndrome; REMS=Risk Evaluation and Mitigation Strategy; RRMM=relapsed or refractory multiple myeloma; USPI=US Prescribing Information.
NEUROLOGIC TOXICITIES
In CARTITUDE-4 and CARTITUDE-1 (N=285)1
NEUROLOGIC TOXICITIES
Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred after CARVYKTI® infusion
| Any grade | GRADE ≥3 |
|---|---|
| 24%(n=69/285) | 7%(19/285) |
- The median time to onset was 10 days (range, 1-101 days) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range, 1-544 days)
- Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune-mediated myelitis in 0.4% of the patients
IMMUNE EFFECTOR CELL–ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)
Patients receiving CARVYKTI® may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.
| Any grade | GRADE ≥3 |
|---|---|
| 13%(n=36/285) | 2%(n=6/285) |
MEDIAN TIME TO ONSET
8 DAYS
(range, 1-28 days)
MEDIAN DURATION
6 DAYS
(range, 1-1229 days)
- ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range, 1-143 days)
- Of patients with ICANS 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively
- The most frequent (≥2%) manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep disorder (2%)
- Monitor patients at least daily for 10 days following CARVYKTI® infusion at the CARVYKTI® Certified Treatment Center for signs and symptoms of ICANS.* Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed
In CARTITUDE-4 (N=188)
| Any grade | GRADE 3 |
|---|---|
| 7% | 0.5% |
In CARTITUDE-1 (N=97)
| Any grade | GRADE 3 |
|---|---|
| 23% | 3% |
*See CARVYKTI® USPI Table 2 Guidance for management of ICANS.
Parkinsonism
| Any grade | GRADE ≥3 |
|---|---|
| 3%(n=8/285) | 2%(n=5/285) |
MEDIAN TIME TO ONSET
56 DAYS
(range, 14-914 days)
MEDIAN DURATION
243.5 DAYS
(range, 62-720 days)
- Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days
- The manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes
- Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment
In CARTITUDE-4 (N=188)
| Any grade | GRADE 3-4 |
|---|---|
| 1% | 0% |
In CARTITUDE-1 (N=97)
| Any grade | GRADE 3-4 |
|---|---|
| 6% | 4% |
Guillain-Barré Syndrome (GBS)
- A fatal outcome following GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins
- Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis
- Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS
- Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS
Immune-mediated myelitis
- Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy
- Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control
- Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause
Peripheral neuropathy
| Any grade | GRADE ≥3 |
|---|---|
| 7%(n=21/285) | 1%(n=3/285) |
MEDIAN TIME TO ONSET
57 DAYS
(range, 1-914 days)
MEDIAN DURATION
149.5 DAYS
(range, 1-692 days)
- Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range, 1-215 days)
- Monitor patients for signs and symptoms of peripheral neuropathies
- Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS
In CARTITUDE-4 (N=188)
| Any grade | GRADE 3 |
|---|---|
| 7% | 0.5% |
In CARTITUDE-1 (N=97)
| Any grade | GRADE 3-4 |
|---|---|
| 7% | 2% |
Cranial nerve palsies
| Any grade | GRADE ≥3 |
|---|---|
| 7%(n=19/285) | 1%(n=1/285) |
MEDIAN TIME TO ONSET
21 DAYS
(range, 17-101 days)
MEDIAN DURATION
70 DAYS
(range, 1-262 days)
- Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range, 1-209 days)
- The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected
- Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptom
In CARTITUDE-4 (N=188)
| Any grade | GRADE 3 |
|---|---|
| 9% | 1% |
In CARTITUDE-1 (N=97)
| Any grade | GRADE 3-4 |
|---|---|
| 3% | 1% |
USPI=US Prescribing Information.
Hemophagocytic Lymphohistiocytosis/
Macrophage Activation Syndrome (HLH/MAS)
In CARTITUDE-4 and CARTITUDE-1 (N=285)1
HLH/MAS is a potentially life-threatening complication
| Any grade |
|---|
| 1%(n=3/285) |
MEDIAN TIME TO ONSET
10 DAYS
(range, 8-99 days)
- All events of HLH/MAS occurred in the setting of ongoing or worsening CRS
- The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure
- Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®
- HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards
CRS=cytokine release syndrome.
Prolonged and/or Recurrent Cytopenias
In CARTITUDE-4 and CARTITUDE-1 (N=285)1
Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion
PROLONGED AND/OR RECURRENT CYTOPENIAS
- Grade 3 or higher cytopenias not resolved by Day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285), and anemia 2% (6/285)
- After Day 60 following CARVYKTI® infusion, 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia, respectively, after initial recovery of their Grade 3 or 4 cytopenia
- Seventy-seven percent (219/285) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia
- Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death
- Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines
HEMATOLOGIC ADVERSE EVENTS IN CARTITUDE-4
Grade 3 or 4 laboratory abnormalities in ≥10% of patients treated with CARVYKTI® (N=188) and standard therapy (N=208)
| Laboratory abnormality | CARVYKTI® (N=188) | Standard Therapy (N=208) |
|---|---|---|
| LYMPHOCYTE COUNT DECREASED | 99 | 62 |
| NEUTROPHIL COUNT DECREASED | 95 | 88 |
| White BLOOD CELLS DECREASED | 94 | 69 |
| PLATELET COUNT DECREASED | 47 | 20 |
| HEMOGLOBIN DECREASED | 34 | 17 |
HEMATOLOGIC ADVERSE EVENTS IN CARTITUDE-1
Grade 3 or 4 laboratory abnormalities in ≥10% of patients treated with CARVYKTI® (N=97)
| Laboratory abnormality | Grade 3-4 (%) |
|---|---|
| Lymphopenia | 99 |
| Neutropenia | 98 |
| White blood cells decreased | 98 |
| ANEMIA | 72 |
| THROMBOCYTOPENIA | 63 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 21 |
Secondary malignancies
In CARTITUDE-4 and CARTITUDE-1 (N=285)1
Patients treated with CARVYKTI® may develop secondary malignancies
- Myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia)
- The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®
- Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy
- Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting
- T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes
- Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples
BCMA=B-cell maturation antigen; CAR=chimeric antigen receptor; CD19=cluster of differentiation 19.
Increased Early Mortality
In CARTITUDE-4 (N=208)1*
- There was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm
- Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm
- Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion
- Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events
- Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events
- The most common adverse events were due to infection (n=12)
- Inform patients of the risk of early mortality
*Evaluated in the intent-to-treat population (419 patients randomized to receive CARVYKTI® (N=208) or standard therapy (N=211)).
Adverse Reactions ≥10%
In CARTITUDE-41
| ADVERSE REACTIONS OBSERVED IN AT LEAST 10% OF PATIENTS TREATED WITH CARVYKTI® AND STANDARD THERAPY IN CARTITUDE-4 STUDY | ||||
| CARVYKTI® N=188 | Standard Therapy N=208 | |||
|---|---|---|---|---|
| System Organ Class (SOC) Preferred term | Any Grade (%) | Grade 3 or Higher (%) | Any Grade (%) | Grade 3 or Higher (%) |
| Gastrointestinal disorders | ||||
| Diarrhea* | 27 | 3 | 27 | 2 |
| Nausea | 20 | 0 | 18 | 1 |
| Constipation | 10 | 0 | 21 | 1 |
| General disorders and administrative site conditions | ||||
| Pyrexia | 79 | 5 | 16 | 1 |
| Fatigue† | 28 | 3 | 15 | 3 |
| Edema‡ | 11 | 1 | 20 | 1 |
| Pain§ | 10 | 1 | 14 | <1 |
| Immune system disorders | ||||
| Hypogammaglobulinemia|| | 94 | 9 | 72 | <1 |
| Cytokine release syndrome | 78 | 3 | <1 | 0 |
| INFECTIONS AND INFESTATIONS | ||||
| Upper respiratory tract infection¶ | 25 | 1 | 40 | 5 |
| Viral infection# | 23 | 4 | 31 | 6 |
| Bacterial infections** | 15 | 6 | 17 | 4 |
| Pneumonia†† | 14 | 9 | 18 | 11 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 10 | 0 | 5 | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal pain‡‡ | 34 | 2 | 47 | 4 |
| Nervous system disorders | ||||
| Headache§§ | 23 | 0 | 13 | 0 |
| Encephalopathy|| || | 11 | 2 | 4 | 1 |
| RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS | ||||
| Cough¶¶ | 15 | 0 | 18 | 0 |
| Hypoxia | 12 | 3 | 1 | 1 |
| Vascular Disorders | ||||
| Hypotension## | 23 | 4 | 3 | 0 |
COVID=coronavirus disease; IgG=immunoglobulin G.
*Diarrhea includes colitis and diarrhea.
†Fatigue includes asthenia, fatigue, and malaise.
‡Edema includes face edema, generalized edema, localized edema, edema peripheral, periorbital edema, peripheral swelling, pulmonary edema, and scrotal edema.
§Pain includes anorectal discomfort, catheter site pain, flank pain, inflammatory pain, pain, pain in jaw, pain of skin, pelvic pain, rhinalgia, and sacral pain.
‖Hypogammaglobulinemia includes subjects with adverse event of hypogammaglobulinemia and/or laboratory IgG levels that fell below 500 mg/dL following CARVYKTI® infusion or standard therapy.
¶Upper respiratory tract infection includes bronchitis, nasal congestion, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, rhinorrhea, rhinovirus infection, sinusitis, upper respiratory tract infection, and viral pharyngitis.
#Viral infection includes adenovirus infection, asymptomatic COVID-19, COVID-19, cytomegalovirus infection, cytomegalovirus infection reactivation, cytomegalovirus viraemia, hepatitis B reactivation, herpes simplex reactivation, herpes virus infection, herpes zoster, human herpesvirus 6 infection, influenza, lymphadenitis viral, metapneumovirus infection, parainfluenza virus infection, parvovirus B19 infection, parvovirus infection, respiratory syncytial virus infection, respiratory tract infection viral, and rotavirus infection.
**Bacterial infection includes bordetella infection, bronchitis bacterial, campylobacter infection, catheter site infection, cellulitis, chalazion, citrobacter infection, clostridium difficile colitis, device related infection, gingivitis, perichondritis, pyelonephritis acute, salmonellosis, skin infection, staphylococcal infection, superinfection bacterial, vascular access site infection, and vascular device infection.
††Pneumonia includes bronchopulmonary aspergillosis, COVID-19 pneumonia, lower respiratory tract infection, metapneumovirus pneumonia, pneumonia, pneumonia moraxella, pneumonia pseudomonal, and pneumonia streptococcal.
‡‡Musculoskeletal pain includes arthralgia, back pain, bone pain, bursitis, musculoskeletal chest pain, musculoskeletal pain, myalgia, myositis, neck pain, non-cardiac chest pain, osteoarthritis, pain in extremity, plantar fasciitis, rotator cuff syndrome, spinal pain, and tendonitis.
§§Headache includes headache and tension headache.
|| ||Encephalopathy includes amnesia, bradyphrenia, confusional state, depressed level of consciousness, disturbance in attention, immune effector cell-associated neurotoxicity syndrome, lethargy, and psychomotor retardation.
¶¶Cough includes cough, productive cough, and upper-airway cough syndrome.
##Hypotension includes hypotension and orthostatic hypotension.
Adverse Reactions ≥10%1
In CARTITUDE-1
| Adverse reactions observed in at least 10% of patients treated with CARVYKTI® in CARTITUDE-1 (N=97) | ||
| System Organ Class (SOC) Preferred Term | Any Grade (%) | Grade 3 or Higher (%) |
|---|---|---|
| Blood and lymphatic system disorders | ||
| Coagulopathy* | 22 | 2 |
| Febrile neutropenia | 10 | 9 |
| Cardiac Disorders | ||
| Tachycardia† | 27 | 1 |
| Gastrointestinal Disorders | ||
| Diarrhea‡ | 33 | 1 |
| Nausea | 31 | 1 |
| Constipation | 22 | 0 |
| Vomiting | 20 | 0 |
| GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS | ||
| Pyrexia | 96 | 5 |
| Fatigue§ | 47 | 7 |
| Chills | 33 | 0 |
| Edema|| | 23 | 0 |
| Immune system disorders | ||
| Cytokine release syndrome¶ | 95 | 5 |
| Hypogammaglobulinemia# | 93 | 2 |
| INFECTIONS AND INFESTATIONS** | ||
| Infections-pathogen unspecified†† | 41 | 19 |
| Upper respiratory tract infection‡‡ | 28 | 3 |
| Viral infections§§ | 23 | 7 |
| Pneumonia|| || | 14 | 13 |
| Sepsis¶¶ | 10 | 7 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 29 | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain## | 48 | 2 |
| Nervous system disorders | ||
| Encephalopathy*** | 30 | 6 |
| Headache | 27 | 0 |
| Dizziness††† | 23 | 1 |
| Motor dysfunction‡‡‡ | 16 | 13 |
| Psychiatric disorders | ||
| Insomnia | 13 | 0 |
| RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS | ||
| Cough§§§ | 39 | 0 |
| Dyspnea|| || || | 23 | 3 |
| Nasal congestion | 15 | 0 |
| Hypoxia | 12 | 4 |
| NEOPLASMS: BENIGN, MALIGNANT, AND UNSPECIFIED (INCL CYSTS AND POLYPS) | ||
| Hematologic malignancy¶¶¶ | 10 | 10 |
| Vascular Disorders | ||
| Hypotension### | 51 | 10 |
| Hypertension | 19 | 6 |
| Hemorrhage**** | 16 | 4 |
CRS=cytokine release syndrome; lgG=immunoglobulin G.
*Coagulopathy includes activated partial thromboplastin time prolonged, coagulopathy, disseminated intravascular coagulation, hypofibrinogenemia, international normalized ratio increased, and prothrombin time prolonged. Also includes terms reported under investigation SOC.
†Tachycardia includes sinus tachycardia, and tachycardia.
‡Diarrhea includes colitis and diarrhea.
§Fatigue includes asthenia, fatigue, and malaise.
‖Edema includes face edema, generalized edema, localized edema, edema peripheral, periorbital edema, peripheral swelling, pulmonary edema, and scrotal edema.
¶Cytokine release syndrome includes CRS, and systemic inflammatory response syndrome.
#Hypogammaglobulinemia includes subjects with adverse event of hypogammaglobulinemia (12%) and/or laboratory IgG levels that fell below 500 mg/dL following CARVYKTI® infusion (92%).
**Infections and infestations System Organ Class Adverse Events are grouped by pathogen type and selected clinical syndromes.
††Infections - pathogen unspecified includes abscess limb, atypical pneumonia, bacteremia, bronchitis, conjunctivitis, enterocolitis infectious, folliculitis, gastroenteritis, lung abscess, lung opacity, osteomyelitis, otitis media, parotitis, perirectal abscess, pneumonia, rash pustular, rhinitis, sepsis, septic shock, sinusitis, skin infection, soft tissue infection, upper respiratory tract infection, and urinary tract infection.
‡‡Upper respiratory tract infection includes human rhinovirus test positive, rhinitis, rhinovirus infection, sinusitis, upper respiratory tract infection, and viral upper respiratory tract infection. Also includes terms reported under investigation SOC. Upper respiratory tract infections may also be included under pathogen categories.
§§Viral infection includes adenovirus test positive, coronavirus infection, cytomegalovirus syndrome, cytomegalovirus viremia, enterovirus infection, gastroenteritis viral, herpes zoster, herpes zoster disseminated, influenza, influenza like illness, oral herpes, parainfluenza virus infection, rhinovirus infection, urinary tract infection viral, and viral upper respiratory tract infection.
‖‖Pneumonia includes atypical pneumonia, lung abscess, lung opacity, pneumocystis jirovecii pneumonia, pneumonia, and pneumonia aspiration.
¶¶Sepsis includes bacteremia, bacterial sepsis, pseudomonal bacteremia, sepsis, septic shock, and staphylococcal bacteremia.
##Musculoskeletal pain includes arthralgia, back pain, bone pain, joint stiffness, muscle strain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, and pain in extremity.
***Encephalopathy includes amnesia, bradyphrenia, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, immune effector cell- associated neurotoxicity syndrome, lethargy, memory impairment, mental impairment, mental status changes, noninfective encephalitis, and somnolence.
†††Dizziness includes dizziness, presyncope, and syncope.
‡‡‡Motor dysfunction includes motor dysfunction, muscle spasms, muscle tightness, muscular weakness, and myoclonus.
§§§Cough includes cough, productive cough, and upper-airway cough syndrome.
‖‖‖Dyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure, and tachypnea.
¶¶¶Hematologic malignancy includes myelodysplastic syndrome and acute myeloid leukemia.
###Hypotension includes hypotension and orthostatic hypotension.
****Hemorrhage includes conjunctival hemorrhage, contusion, ecchymosis, epistaxis, eye contusion, hematochezia, hemoptysis, infusion site hematoma, oral contusion, petechiae, post procedural hemorrhage, pulmonary hemorrhage, retinal hemorrhage, and subdural hematoma.
LONG-TERM SAFETY
In CARTITUDE-4 at 33.6 Months*
You are now viewing a subsequent follow-up analysis from the CARTITUDE-4 trial. This information is not included in the current USPI.
The safety data described in this section reflect the CARTITUDE-4 follow-up safety analysis at 33.6 months. The safety population of CARVYKTI® represents all patients who were randomized to CARVYKTI® (N=208)2*
| INFECTIONS | CARVYKTI® (N=208) | Standard Therapy (N=208) |
|---|---|---|
| Treatment-emergent infections, (%) | ||
| All Grade | 63.5 | 76.4 |
| Grade 3/4 | 28.4 | 29.8 |
| Deaths due to TE- and non-TE infections, n | 16 | 19 |
| In first year, n | 13 | 8 |
| In second year, n | 2 | 8 |
| CAUSE OF DEATH | CARVYKTI® (N=208) | Standard Therapy (N=208) |
|---|---|---|
| Deaths, n | 50 | 82 |
| Due to progressive disease | 21 | 51 |
| Due to TEAE | 12 | 8 |
| SECONDARY PRIMARY MALIGNANCIES | CARVYKTI® (N=208) | Standard Therapy (N=208) |
|---|---|---|
| SPMs, n (%) | 27 (13.0) | 24 (11.5) |
| Hematologic,† n (%) | 7 (3.4) | 1 (0.5) |
| MDS, n | 4 | 0 |
| Progresses to AML, n | 2 | - |
| AML, n | 1 | 0 |
| Peripheral T-cell lymphoma, n | 2 | 0 |
| EBV-associated lymphoma, n | 0 | 1 |
| Cutaneous/non-invasive† | 15 (7.2) | 15 (7.2) |
| Non-cutaneous/invasive† | 6 (2.9) | 8 (3.8) |
- Both arms had Grade 3/4 TEAE around 97%; most frequently cytopenia
- There have been no additional incidences of cranial nerve palsy or MNT since the previous data cutoff, as reported by San-Miguel J, et al. in the NEJM 15.9-month follow-up (see reference 3), whether patients received CARVYKTI® as study treatment (n=176) or received CARVYKTI® as subsequent therapy 3
- Among the patients who received CARVYKTI® as a study treatment (n=176) in CARTITUDE-4, there are a total of 16 cases of CNP, of which 14 cases recovered, and 1 case of ongoing MNT3
AML=acute myeloid leukemia; CNP=cranial nerve palsy; EBV=Epstein-Barr virus; LT=long term; MDS=myelodysplastic syndrome; MNT=movement and neurocognitive treatment-emergent adverse event; SPM=second primary malignancy; TE=treatment emergent; TEAE=treatment-emergent adverse event; USPI=US Prescribing Information.
*Median was 33.6 months (follow-up analysis) and 15.9 months (primary analysis) in the Intent-to-Treat Analysis Set.
†Multiple SPMs could occur in the same patient.