Carvykti · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-099153 · has-adverse-reaction-information · PDF-Seite 14

Summary of the safety profile The safety of CARVYKTI was evaluated in 396 adult patients with multiple myeloma infused with CARVYKTI in three open label clinical trials: Study MMY2001 (N=106), which included patients from the main Phase 1b/2 cohort (United States; n=97) and an additional cohort (Japan; n=9), Phase 2 Study MMY2003 (N=94) and Phase 3 Study MMY3002 (N=196). Patients who complete Study MMY2001, MMY2003, or MMY3002 are eligible to enroll in a separate long-term follow-up study (MMY4002). The most common CARVYKTI adverse reactions (≥20%) were neutropenia (90%), pyrexia (85%), CRS (83%), thrombocytopenia (60%), anemia (60%), musculoskeletal pain (40%), lymphopenia (38%), fatigue (35%), leukopenia (34%), hypotension (34%), hypogammaglobulinaemia (33%), diarrhea (32%), upper respiratory tract infection (32%), transaminase elevation (26%), headache (25%), nausea (23%), and cough (22%). Serious adverse reactions occurred in 44% of patients; serious adverse reactions reported in ≥2% of patients were CRS (11%), pneumonia (9%), sepsis (5%), viral infection (5%), neutropenia (4%), cranial nerve palsies, (4%), ICANS (4%), encephalopathy (3%), upper respiratory tract infection (3%), bacterial infections (2%), gastroenteritis (2%), febrile neutropenia (2%), thrombocytopenia (2%), haemophagocytic lymphohistiocytosis (2%), motor dysfunction (2%), dyspnea (2%), diarrhea (2%), and renal failure (2%). 14 The most common (≥5%) Grade ≥ 3 non-haematological adverse reactions were transaminase elevation (11%), pneumonia (11%), febrile neutropenia (8%), sepsis (7%), pyrexia (7%), Gamma- glutamyltransferase increased (6%), hypotension (6%), bacterial infection (5%), and hypogammaglobulinaemia (5%). The most common (≥20%) Grade ≥3 haematological abnormalities were neutropenia (89%), thrombocytopenia (45%), anaemia (44%), lymphopenia (36%), and leukopenia (33%). Tabulated list of adverse reactions Table 4 summarises the adverse reactions that occurred in patients receiving CARVYKTI. Within each system organ class, the adverse reactions are ranked by frequency. Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness using the following convention: 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); not known (cannot be estimated from the available data). Table 4: Adverse reac

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099149 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. Contraindications of the lymphodepleting chemotherapy and supportive therapy should be considered.

HOS-099148 · has-indication-information · PDF-Seite 2

CARVYKTI is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. 2

HOS-099151 · has-interaction-information · PDF-Seite 13

No pharmacokinetic or pharmacodynamic drug interaction studies have been performed with CARVYKTI. The co-administration of agents known to inhibit T cell function has not been formally studied. The co-administration of agents known to stimulate T cell function has not been investigated and the effects are unknown. Some patients in the clinical trials on CARVYKTI required tocilizumab, corticosteroids and anakinra for management of CRS. CARVYKTI continues to expand and persist following tocilizumab administration. In Study MMY2001, patients treated with tocilizumab (n=68) had 81% and 72% higher CARVYKTI Cmax and AUC0-28d, respectively, as compared to patients (n=29) who did not receive tocilizumab. Patients who received corticosteroids (n=28) had 75% and 112% higher Cmax and AUC0-28d, respectively, compared with patients who did not receive corticosteroids (n=69). In addition, patients who received anakinra (n=20) had 41% and 72% higher Cmax and AUC0-28d, respectively, compared with patients who did not receive anakinra (n=77). In Study MMY3002, the results related to tocilizumab and corticosteroid were consistent with Study MMY2001. Live vaccines The safety of immunisation with live viral vaccines during or following CARVYKTI treatment has not been studied. As a precautionary measure, vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI treatment, and until immune recovery following treatment with CARVYKTI.

HOS-099152 · has-pregnancy-information · PDF-Seite 13

Women of childbearing potential/Contraception in males and females Pregnancy status for females of childbearing potential should be verified prior to starting treatment with CARVYKTI. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with CARVYKTI. In clinical trials, female patients of childbearing potential were advised to practice a highly effective method of contraception, and male patients with partners of childbearing potential or whose partners were pregnant were instructed to use a barrier method of contraception, until one year after the patient has received CARVYKTI. 13 See the prescribing information for lymphodepleting chemotherapy for information on the need for contraception in patients who receive the lymphodepleting chemotherapy. Pregnancy There are no available data on the use of CARVYKTI in pregnant women. No reproductive and developmental toxicity animal studies have been conducted with CARVYKTI. It is not known whether CARVYKTI has the potential to be transferred to the foetus and cause foetal toxicity. Therefore, CARVYKTI is not recommended for women who are pregnant, or for women of childbearing potential not using contraception. Pregnant women should be advised there may be risks to the foetus. Pregnancy after CARVYKTI therapy should be discussed with the treating physician. Pregnant women who have received CARVYKTI may have hypogammaglobulinaemia. Assessment of immunoglobulin levels in newborns of mothers treated with CARVYKTI should be considered. Breast-feeding It is unknown whether CARVYKTI is excreted in human milk. Women who are breast-feeding should be advised of the potential risk to the breast-fed infant. Following administration of CARVYKTI, the decision to consider breast-feeding should be discussed with the treating physician. Fertility There are no data on the effect of CARVYKTI on fertility. Effects of CARVYKTI on male and female fertility have not been evaluated in animal studies (see section 5.3).

HOS-099150 · has-warning-information · PDF-Seite 4

Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability, the name of the medicinal product, the batch number and the name of the treated patient should be kept for a period of 30 years after the expiry date of the medicinal product. General Autologous use CARVYKTI is intended solely for autologous use and must not, under any circumstances, be administered to other patients. CARVYKTI must not be infused if the information on the product labels and Lot Information Sheet does not match the patient’s identity. Clinical assessment prior to CARVYKTI infusion CARVYKTI infusion should be delayed if a patient has any of the following conditions:  clinically significant active infection or inflammatory disorders, 4  grade ≥ 3 non-haematologic toxicities of cyclophosphamide and fludarabine lymphodepletion regimen, except for Grade 3 nausea, vomiting, diarrhoea, or constipation. CARVYKTI infusion should be delayed until resolution of these events to Grade ≤ 1,  active graft versus host disease. Patients with active or prior history of significant central nervous system (CNS) disease or inadequate renal, hepatic, pulmonary, or cardiac function are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention. There is no experience of use of CARVYKTI in patients with CNS involvement of myeloma or other pre-existing, clinically relevant CNS illnesses. The efficacy/safety of CARVYKTI in patients previously exposed to other anti-BCMA treatments is unknown. There is limited evidence available on efficacy/safety of CARVYKTI in re-treated patients. Rapidly progressing disease When considering patients for CARVYKTI treatment, physicians should assess the impact of rapidly progressing disease on the ability of patients to receive CAR-T infusion. Some patients may not benefit from CARVYKTI treatment due to potential increased risk of early death if disease progresses rapidly during bridging therapy. Monitoring after infusion Patients should be monitored daily for 14 days after the CARVYKTI infusion at a qualified clinical facility, and then periodically for an additional 2 weeks after CARVYKTI infusion, for signs and symptoms of CRS, neurologic events and other toxicities (see section 4.4). Patients should be instructed to remain within proximity of a qualified cl

Auszug; vollständigen Abschnitt im Original lesen.