There are no available data on isatuximab use in pregnant women. Animal reproduction toxicity studies have not been conducted with isatuximab. Immunoglobulin G1 monoclonal antibodies are known to cross the placenta after the first trimester of pregnancy. The use of isatuximab in pregnant women is not recommended.
It is unknown whether isatuximab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; however, a risk to the breast-fed child cannot be excluded during this short period just after birth. For this specific period, a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from isatuximab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Afterwards, isatuximab could be used during breastfeeding if clinically needed.
Women of childbearing potential treated with isatuximab should use effective contraception during treatment and for 5 months after cessation of treatment.
No human and animal data are available to determine potential effects of isatuximab on fertility in males and females.
For other medicinal products that are administered with isatuximab, refer to the respective current summary of product characteristics.
Isatuximab has no or negligible influence on the ability to drive and use machines. Fatigue and dizziness have been reported in patients taking isatuximab and this should be taken into account when driving or using machines.
In ICARIA-MM, the most frequent adverse reactions (> 20%) are neutropenia (46.7%), infusion reactions (38.2%), pneumonia (30.9%), upper respiratory tract infection (28.3%), diarrhoea (25.7%) and bronchitis (23.7%). Serious adverse reactions occurred in 61.8% of patients receiving Isa-Pd. The most frequent serious adverse reactions are pneumonia (25.7%) and febrile neutropenia (6.6%). Permanent discontinuation of treatment because of adverse reactions was reported in 7.2% of patients treated with Isa-Pd. Adverse reactions with a fatal outcome during treatment were reported in 7.9% of patients treated with Isa-Pd (those occurring in more than 1% of patients were pneumonia occurring in 1.3% of patients and other infections occurring in 2.0% of patients).
In IKEMA, the most frequent adverse reactions (≥ 20%) are infusion reactions (45.8%), hypertension (36.7%), diarrhoea (36.2%), upper respiratory tract infection (36.2%), pneumonia (28.8%), fatigue (28.2%), dyspnoea (27.7%), insomnia (23.7%), bronchitis (22.6%), and back pain (22.0%). Serious adverse reactions occurred in 59.3% of patients receiving Isa-Kd. The most frequent serious adverse reaction is pneumonia (21.5%). Permanent discontinuation of treatment because of adverse reactions was reported in 8.5% of patients treated with Isa-Kd. Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients treated with Isa-Kd (those occurring in more than 1% of patients were pneumonia and cardiac failure both occurring in 1.1% of patients).
In IMROZ, the most frequent adverse reactions (≥20%) are diarrhoea (54.8%), peripheral sensory neuropathy (54.4%), pneumonia (39.9%), cataract (38.0%), constipation (35.7%), fatigue (34.6%), upper respiratory tract infections (34.2%), oedema peripheral (32.7%), neutropenia (30.0% as an adverse reaction), infusion reaction (23.6%), insomnia (22.4%), Covid-19 (22.4%), back pain (22.1%), bronchitis (22.1%). and asthenia (21.7%), Serious adverse reactions occurred in 70.7% of patients receiving Isa-VRd. The most frequent serious adverse reaction was pneumonia (29.7%, including Covid-19 pneumonia). Adverse reactions with a fatal outcome during treatment (Grade 5 TEAEs) were reported in 11% of patients with Isa-VRd including Grade 5 infectious TEAEs occurring in 6.5% of patients. Permanent discontinuation of treatment because of adverse reactions was reported in 22.8% of patients treated with Isa-VRd.
In GMMG-HD7, during the induction period, the most frequent adverse reactions (≥10%) are polyneuropathy (18.8%), neutropenia (16.1%), and infusion related reactions (12.4%). Serious adverse reactions occurred in 35.2% of patients receiving Isa-VRd. The most frequent serious adverse reactions are pneumonia (3.6%), pyrexia (3.3%), and diarrhoea (2.1%). Adverse reactions with a fatal outcome during treatment (Grade 5 TEAEs) were reported in 1.2% of patients treated with Isa-VRd (due to COVID-19, pneumonia influenza, septic shock, and haemorrhage intracranial, each reported in 0.3% of patients). Permanent discontinuation of treatment because of adverse reactions was reported in 3% of patients treated with Isa-VRd.
Adverse reactions are described using the NCI Common Toxicity Criteria, the COSTART and the MedDRA terms. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); frequency not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
The adverse reactions were reported in clinical studies and post-market settings.
Table 1. Adverse reactions reported in patients with multiple myeloma treated with isatuximab in combination with pomalidomide and dexamethasone:
| System Organ Class Preferred Term | Adverse reaction | Frequency | Incidence (N=244) | |
|---|---|---|---|---|
| Any Grade | Grade ≥3 | |||
| Infections and infestations | Pneumoniaab | Very common | 34.8% | 27.9% |
| Upper respiratory tract infection | Very common | 40.2% | 3.3% | |
| Bronchitis | Very common | 20.9% | 3.7% | |
| Herpes zoster | Common | 2.5% | 0.4% | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps)c | Skin cancer | Common | 4.9% | 1.6% |
| Solid tumour (non-skin cancer) | Common | 2.9% | 1.6% | |
| Haematology malignancy | Uncommon | 0.4% | 0.4% | |
| Blood and lymphatic system disorders | Neutropenia | Very common | 52.5% | 51.6% |
| Thrombocytopenia | Very common | 12.7% | 11.9% | |
| Febrile neutropenia | Common | 7.4% | 7.4% | |
| Anaemia | Common | 6.1% | 4.5% | |
| Lymphopenia | Not known | - | - | |
| Immune system disorders | Anaphylactic reactiond | Uncommon | 0.3% | 0.3% |
| Metabolism and nutrition disorders | Decreased appetite | Very common | 11.5% | 1.2% |
| Cardiac disorders | Atrial fibrillation | Common | 5.7% | 2.5% |
| Respiratory, thoracic and mediastinal disorders | Dyspnoea | Very common | 25.8% | 5.7% |
| Gastrointestinal disorders | Diarrhoea | Very common | 34.0% | 2.5% |
| Nausea | Very common | 22.1% | 0% | |
| Vomiting | Very common | 14.8% | 0.8% | |
| Investigations | Weight decreased | Common | 4.9% | 0% |
| Injury, poisoning and procedural complications | Infusion reactionb | Very common | 39.3% | 2.0% |
a The term pneumonia is a grouping of the following terms: atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenza, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, pneumonia bacterial, haemophilus infection, lung infection, pneumonia fungal and pneumocystis jirovecii pneumonia.
b See "Description of selected adverse reactions".
c Based on second primary malignancies reported during study treatment period and during post-treatment period.
d Based on post-marketing adverse reactions.
Table 2a. Adverse reactions reported in patients with multiple myeloma treated with isatuximab in combination with carfilzomib and dexamethasone:
| System Organ Class Preferred Term | Adverse reaction | Frequency | Incidence (N=177) | |
|---|---|---|---|---|
| Any Grade | Grade ≥3 | |||
| Infections and infestations | Pneumoniabc | Very common | 28.8% | 20.9% |
| Upper respiratory tract infection | Very common | 36.2% | 3.4% | |
| Bronchitis | Very common | 22.6% | 2.3% | |
| Herpes zoster | Common | 2.3% | 0.6% | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps)d | Skin cancers | Common | 7.3% | 1.7% |
| Solid tumours (non-skin cancers) | Common | 4.0% | 3.4% | |
| Blood and lymphatic system disorders | Anaemia | Common | 5.1% | 4.5% |
| Neutropenia | Common | 4.5% | 4.0% | |
| Thrombocytopenia | Common | 2.8% | 2.3% | |
| Lymphopenia | Not known | - | - | |
| Immune system disorders | Anaphylactic reactione | Uncommon | 0.3% | 0.3% |
| Vascular disorders | Hypertension | Very common | 36.7% | 20.3% |
| Respiratory, thoracic and mediastinal disorders | Dyspnoea | Very common | 27.7% | 5.1% |
| Cough | Very common | 19.8% | 0% | |
| Gastrointestinal disorders | Diarrhoea | Very common | 36.2% | 2.8% |
| Vomiting | Very common | 15.3% | 1.1% | |
| General disorders and administration site conditions | Fatigue | Very common | 28.2% | 3.4% |
| Injury, poisoning and procedural complications | Infusion reactionc | Very common | 45.8% | 0.6% |
a Cut-off date of 07-Feb-2020. Median follow-up time = 20.73 months.
b The term pneumonia is a grouping of the following terms: atypical pneumonia, pneumocystis jirovecii pneumonia, pneumonia, pneumonia influenza, pneumonia legionella, pneumonia streptococcal, pneumonia viral, and pulmonary sepsis.
c See "Description of selected adverse reactions".
d Cut-off date of 07-Feb-2023. Median follow-up time = 56.61 months. Based on second primary malignancies reported during study treatment period and during post-treatment period.
e Based on post-marketing adverse reactions.
Table 3. Adverse reactions reported in patients with newly diagnosed multiple myeloma, transplant ineligible, treated with isatuximab in combination with bortezomib, lenalidomide, and dexamethasone:
| System Organ Class Preferred Term | Adverse reaction | Frequency | Incidence (N=336) | |
|---|---|---|---|---|
| Any Grade | Grade ≥3 | |||
| Infections and infestations | Pneumoniaa | Very common | 34.2% | 24.1% |
| Bronchitis | Very common | 22.6% | 3.0% | |
| Covid-19 | Very common | 19.9% | 1.2% | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Skin cancer | Common | 8.0% | 2.7% |
| Solid tumour (non-skin cancer) | Common | 5.7% | 3.6% | |
| Haematology malignancy | Uncommon | 0.9% | 0.3% | |
| Blood and lymphatic system disorders | Neutropenia | Very common | 28.0% | 27.1% |
| Thrombocytopenia | Very common | 13.4% | 10.7% | |
| Anaemia | Common | 6.3% | 2.7% | |
| Lymphopenia | Not known | = | - | |
| Immune system disorders | Anaphylactic reaction | Uncommon | 0.3% | 0.3% |
| Eye disorders | Cataract | Very common | 36.0% | 13.1% |
| Gastrointestinal disorders | Diarrhoea | Very common | 56.8% | 8.3% |
| Vomiting | Common | 9.5% | 0.3% | |
| General disorders and administration site conditions | Fatigue | Very common | 32.7% | 6.5% |
| Injury, poisoning and procedural complications | Infusion reaction | Very common | 27.4% | 0.6% |
a The term pneumonia is a grouping of the following terms: Atypical pneumonia, Bronchopulmonary aspergillosis, Covid-19 pneumonia, Pneumocystis jirovecii pneumonia, Pneumonia, Pneumonia bacterial, Pneumonia haemophilus, Pneumonia influenzal, Pneumonia klebsiella, Pneumonia legionella, Pneumonia pneumococcal, Pneumonia pseudomonal, Pneumonia respiratory syncytial viral, Pneumonia viral, Pulmonary sepsis, Tuberculosis.
MedDRA 26.0
Table 4. Adverse reactions reported during induction period in patients with newly diagnosed multiple myeloma, transplant eligible, treated with isatuximab in combination with bortezomib, lenalidomide, and dexamethasone:
| System Organ Class Preferred Term | Adverse reaction | Frequency | Incidence (N=330) | |
|---|---|---|---|---|
| Any Grade | Grade ≥3 | |||
| Infections and infestations | Pneumoniaab | Common | 5.5% | 4.8% |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Solid tumours (non- skin cancers) | Uncommon | 0.3% | 0.3% |
| Blood and lymphatic system disorders | Neutropenia | Very common | 16.1% | 16.1% |
| Anaemia | Common | 3.6% | 3.6% | |
| Thrombocytopenia | Common | 4.5% | 4.5% | |
| Lymphopenia | Common | 3.3% | 3.3% | |
| Immune system disorders | Anaphylactic reaction | Uncommon | 0.3% | 0.3% |
| Investigations | Neutrophil count decreased | Common | 7.3% | 7.3% |
| Injury, poisoning and procedural complications | Infusion reactionb | Very common | 12.7% | 0.9% |
a The term pneumonia is a grouping of the following terms: Pneumonia, Pneumonia influenza, Atypical pneumonia, Pneumonia fungal.
b See "Description of selected adverse reactions".
In ICARIA-MM, infusion reactions were reported in 58 patients (38.2%) treated with isatuximab. All patients who experienced infusion reactions, experienced them during the 1st infusion of isatuximab, with 3 patients (2.0%) also having infusion reactions at their 2nd infusion, and 2 patients (1.3%) at their 4th infusion. Grade 1 infusion reactions were reported in 3.9%, Grade 2 in 31.6%, Grade 3 in 1.3%, and Grade 4 in 1.3% of the patients. All infusion reactions were reversible and resolved the same day in 98% of the infusions. Signs and symptoms of Grade 3 or 4 infusion reactions included dyspnoea, hypertension, and bronchospasm.
The incidence of infusion interruptions because of infusion reactions was 28.9%. The median time to infusion interruption was 55 minutes.
Discontinuations from treatment due to infusion reaction were reported in 2.6% of patients in Isa-Pd group.
In IKEMA, infusion reactions were reported in 81 patients (45.8%) treated with Isa-Kd. Grade 1 infusion reactions were reported in 13.6%, Grade 2 in 31.6%, and Grade 3 in 0.6% of the patients treated with Isa-Kd. All infusion reactions were reversible and resolved the same day in 73.8% of episodes in Isa-Kd patients and in more than 2 days in 2.5% of episodes in Isa-Kd patients. Signs and symptoms of Grade 3 infusion reactions included dyspnoea and hypertension. The incidence of patients with isatuximab infusion interruptions because of infusion reactions was 29.9%. The median time to isatuximab infusion interruption was 63 minutes. Isatuximab was discontinued in 0.6% of patients due to infusion reactions.
In IMROZ, infusion reactions were reported in 63 patients (24.0%) treated with Isa-VRd. Grade 1 IRs were reported in 1.9%, Grade 2 in 21.3%, Grade 3 in 0.4%, and Grade 4 in 0.4% of the patients treated with Isa-VRd. The IRs started on the infusion day in all patients, mostly during the first isatuximab infusion, and resolved the same day in 97.3% of patients. All IRs resolved. Signs and symptoms of Grade 3 or 4 IRs included hypertension, bronchospasm, and hypoxia. The incidence of patients with isatuximab infusion interruptions because of infusion reactions was 20.9%. The median time to isatuximab infusion interruption was 66.0 minutes. Isatuximab was discontinued in 0.8% of patients due to infusion reactions.
In GMMG-HD7, during the induction period, infusion reactions were reported in 42 patients (12.7%) treated with Isa-VRd. Grade 1 infusion reactions were not collected in the study. Grade 2 infusion reactions were reported in 11.8%, Grade 3 in 0.6%, and Grade 4 in 0.3% of the patients treated with Isa-VRd. All infusion reactions resolved. The incidence of patients with isatuximab infusion interruptions because of infusion reactions was 7.6%. Isatuximab was discontinued in 0.3% of patients due to infusion reactions.
In ICARIA-MM, the incidence of Grade 3 or higher infections was 42.8%. Pneumonia was the most commonly reported severe infection with Grade 3 reported in 21.7% of patients in the Isa-Pd group compared to 16.1% in the Pd group, and Grade 4 in 3.3% of patients in the Isa-Pd group compared to 2.7% in the Pd group. Discontinuations from treatment due to infection were reported in 2.6% of patients in the Isa-Pd group compared to 5.4% in the Pd group. Fatal infections were reported in 3.3% of patients in the Isa-Pd group and 4.0% in the Pd group. In IKEMA, the incidence of Grade 3 or higher infections was 38.4%. Pneumonia was the most commonly reported severe infection with Grade 3 reported in 15.8% of patients in the Isa-Kd group compared to 10.7% in the Kd group, and Grade 4 in 3.4% of patients in the Isa-Kd group compared to 2.5% in the Kd group. Treatment was discontinued due to infection in 2.8% of patients in the Isa-Kd group compared to 4.9% in the Kd group. Fatal infections were reported in 2.3% of patients in the Isa-Kd group and 0.8% in the Kd group. In IMROZ, the incidence of Grade 3 or higher infections was 44.9% in the Isa-VRd group and 38.1% in the VRd group. Pneumonia was the most commonly reported severe infection with Grade 3 reported in 25.1% of patients in the Isa-VRd group compared to 15.5% in the VRd group, Grade 4 in 2.3% of patients in the Isa-VRd group compared to 3.9% in the VRd group. Grade 5 pneumonia, based on preferred term, occurred in 1.5% of patients in the Isa-VRd group compared to 1.1% in the VRd group. Discontinuations from treatment due to infection were reported in 8.4% of patients in the Isa- VRd group compared to 9.4% in the VRd group. Fatal infections were reported in 6.5% of patients in the Isa-VRd group and 4.4% in the VRd group. In GMMG-HD7, during the induction period, the incidence of Grade 3 or higher infections was 13% in the Isa-VRd group and 10.1% in the VRd group. Pneumonia was the most commonly reported severe infection with Grade ≥3 reported in 3.9% of patients in the Isa-VRd group compared to 2.1% in the VRd group. Discontinuations from treatment due to infection were reported in 0.3% of patients in the Isa-VRd group compared to 0.9% in the VRd group.
In relapsed and refractory multiple myeloma clinical studies, herpes zoster was reported in 2.0% of patients. In ICARIA-MM, the incidence of herpes zoster was 4.6% in the Isa-Pd group compared to 0.7% in the Pd group, and in IKEMA, incidence was 2.3% in the Isa-Kd group compared to 1.6% in the Kd group. In newly diagnosed multiple myeloma clinical trials, herpes zoster was reported in 3.3% of patients. In IMROZ, the incidence of herpes zoster was 5.7% in the Isa-VRd group compared to 5.5% in the VRd group. In GMMG-HD7, during the induction period, the incidence of herpes zoster was 0.9% in the Isa-VRd group compared to 0.3% in the VRd group.
In IKEMA, cardiac failure (including cardiac failure, cardiac failure congestive, cardiac failure acute, cardiac failure chronic, left ventricular failure, and pulmonary oedema) was reported in 7.3% of patients with the Isa-Kd group (4.0% of Grade ≥3) and in 6.6% of patients with the Kd group (4.1% of Grade ≥3). Serious cardiac failure was observed in 4.0% of patients in the Isa-Kd group and in 3.3% of patients in the Kd group. Cardiac failure with a fatal outcome during treatment was reported in 1.1% of patients in the Isa-Kd group and not reported in the Kd group (see the current prescribing information for carfilzomib).
Table 5. Haematology laboratory abnormalities in patients receiving isatuximab combined with pomalidomide and dexamethasone versus pomalidomide and dexamethasone (ICARIA-MM):
| Laboratory parameter | Isatuximab + Pomalidomide + Dexamethasone n (%) (N=152) | Pomalidomide + Dexamethasone n (%) (N=147) | ||||
|---|---|---|---|---|---|---|
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| Anaemia | 151 (99.3) | 48 (31.6) | 0 | 145 (98.6) | 41 (27.9) | 0 |
| Neutropenia | 146 (96.1) | 37 (24.3) | 92 (60.5) | 137 (93.2) | 57 (38.8) | 46 (31.3) |
| Lymphopenia | 140 (92.1) | 64 (42.1) | 19 (12.5) | 137 (93.2) | 52 (35.4) | 12 (8.2) |
| Thrombocytopenia | 127 (83.6) | 22 (14.5) | 25 (16.4) | 118 (80.3) | 14 (9.5) | 22 (15.0) |
The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period.
Table 6. Haematology laboratory abnormalities in patients receiving isatuximab combined with carfilzomib and dexamethasone versus carfilzomib and dexamethasone (IKEMA):
| Laboratory parameter | Isatuximab + Carfilzomib + Dexamethasone % (N=177) | Carfilzomib + Dexamethasone % (N=122) | ||||
|---|---|---|---|---|---|---|
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| Anaemia | 99.4 | 22.0 | 0 | 99.2 | 19.7 | 0 |
| Neutropenia | 54.8 | 17.5 | 1.7 | 43.4 | 6.6 | 0.8 |
| Lymphopenia | 94.4 | 52.0 | 16.9 | 95.1 | 43.4 | 13.9 |
| Thrombocytopenia | 94.4 | 18.6 | 11.3 | 87.7 | 15.6 | 8.2 |
The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period.
Table 7. Haematology laboratory abnormalities in patients receiving isatuximab combined with bortezomib, lenalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone (IMROZ and TCD13983):
| Laboratory parameter | Isatuximab + Bortezomib + Lenalidomide + Dexamethasone (N=336) | Bortezomib + Lenalidomide + Dexamethasone (N=181) | ||||
|---|---|---|---|---|---|---|
| All Grades | Grade 3 | Grade 4 | All Grades | Grade 3 | Grade 4 | |
| Anaemia | 99.1% | 15.8% | 0% | 97.8% | 16.0% | 0% |
| Lymphopenia | 96.1% | 45.5% | 18.5% | 92.3% | 37.6% | 15.5% |
| Thrombocytopenia | 94.6% | 16.7% | 14.6% | 84.5% | 19.3% | 8.3% |
| Neutropenia | 86.9% | 35.4% | 17.3% | 80.1% | 28.2% | 8.8% |
The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period.
CTCAE version: 4.03.
Table 8. Haematology laboratory abnormalities in patients receiving isatuximab combined with bortezomib, lenalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone during induction period (GMMG-HD7):
| Laboratory parameter | Isatuximab + Bortezomib + Lenalidomide + Dexamethasone (N=330) | Bortezomib + Lenalidomide + Dexamethasone (N=328) | ||||
|---|---|---|---|---|---|---|
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| Anaemia | 80.0% | 1.6% | 0% | 79.7% | 0.9% | 0% |
| Neutropenia | 30.9% | 3.1% | 2.8% | 22.9 | 2.5% | 1.9% |
| Lymphopenia | 54.4% | 15.6% | 2.2% | 67.4% | 18.7% | 5.1% |
| Thrombocytopenia | 21.6% | 0.6% | 0.9% | 20.3% | 0.3% | 0% |
The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period.
Of the total number of patients in clinical studies of isatuximab, 42.7% (763 patients) were less than 65, 43.2% (772 patients) were 65-74, and 14.1% (252 patients) were 75 or older. Differences in safety were observed between older versus younger age groups. Grade >3 TEAEs were reported in 64.7% of patients less than 65, 79.7% of patients 65-74 and 76.6% of patients 75 or older, Grade 5 TEAEs were reported in 5.6% of patients less than 65, 7.5% of patients 65-74, and 12.3% of patients 75 or older. Serious TEAEs were reported in 46.7% of patients less than 65, 59.3% of patients 65-74, and 61.1% of patients 75 or older. TEAEs leading to definitive treatment discontinuation were reported in 6.4% of patients less than 65, 14.4% of patients 65-74, and 15.9% of patients 75 or older.
In the IMROZ study, no Grade 5 TEAEs were reported in patients less than 65, they were reported in 10.7% of patients 65-74, and in 13.2% of patients 75 or older. In GMMG-HD7 study, only patients until 70 years of age were included. During the induction period, Grade ≥3 TEAEs were reported in 59.7% of patients less than 65 and in 77.8% of patients 65 or older, TEAEs leading to definitive treatment discontinuation were reported in 1.6% of patients less than 65 and 8.3% of patients 65 or older, and Grade 5 TEAEs were reported in 0.8% of patients less than 65 and in 2.8% of patients 65 or older.
Across 9 clinical studies (N=1023) in relapsed or refractory multiple myeloma (RRMM) with isatuximab single agent and combination therapies including ICARIA-MM and IKEMA, the incidence of treatment emergent anti-drug antibodies (ADAs) was <2%. No effect of ADAs was observed on pharmacokinetics, safety or efficacy of isatuximab. Across 3 clinical studies (N=383) in newly diagnosed multiple myeloma (NDMM) with isatuximab in combination therapy with bortezomib, lenalidomide, and dexamethasone, including IMROZ and GMMG-HD7, ADA incidence ranged from 9.1% to 21.6%. In IMROZ and GMMG-HD7, 60% (15 out of 25) and 50% (4 out of 8) of the treatment induced ADA were neutralizing, respectively. In NDMM, a trend to lower exposure was observed in ADA-positive patients. No effect of ADAs was observed on efficacy of isatuximab. No conclusions can be drawn on safety due to the small subgroup of ADA positive patients.
In a phase 2 single-arm study conducted in 67 paediatric patients with relapsed or refractory acute lymphoblastic leukaemia or acute myeloid leukaemia, all evaluable for safety, Grade ≥3 TEAEs was reported in 79.1% of patients. The most common Grade ≥3 TEAEs occurring in >10% of patients included febrile neutropenia (41.8%), septic shock (11.9%), and stomatitis (10.4%). The addition of isatuximab to standard chemotherapies did not modify the expected safety profile observed with standard chemotherapies in this paediatric population and was consistent with isatuximab safety profile for adults with multiple myeloma in ICARIA and IKEMA studies.
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