CARVYKTI®
(ciltacabtagene autoleucel)
Medical inquiries
This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.
CARVYKTI® (ciltacabtagene autoleucel)
Medical Information
CARVYKTI - Apheresis/Leukapheresis in CARTITUDE-1 and CARTITUDE-4
Last Updated: 01/30/2025
Summary
- CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of CARVYKTI in 97 patients with RRMM.1
- 4 - Study enrollment was defined at the day of apheresis/leukapheresis. Enrolled patients underwent apheresis to acquire peripheral blood mononuclear cells (PBMC).3
- Patients' blood was apheresed according to institutional standards, with a collection target of 6×109
PBMC (range 2×109–20×109). Two apheresis collections may have been performed to attain this target. 1
- Patients' blood was apheresed according to institutional standards, with a collection target of 6×109
- CARVYKTI was manufactured from the patients’ T cells selected from the apheresis product.
3 - Re-apheresis was permitted for patients whom apheresis or manufacturing failed. Patients were withdrawn from the study if unable to manufacture CARVYKTI after 2 apheresis attempts.3
- All patients that were enrolled in CARTITUDE-1 (N=113) underwent apheresis. A total of 101 patients were lymphodepleted, and 97 patients were treated with
CARVYKTI.1
- All patients that were enrolled in CARTITUDE-1 (N=113) underwent apheresis. A total of 101 patients were lymphodepleted, and 97 patients were treated with
- Please see below for eligibility criteria for apheresis from the CARTITUDE-1 study protocol.3
- Study enrollment was defined at the day of apheresis/leukapheresis. Enrolled patients underwent apheresis to acquire peripheral blood mononuclear cells (PBMC).3
- CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO®
[daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior line(s) of therapy (LOT).5 6 - Patients randomized to the CARVYKTI arm underwent apheresis to acquire PBMCs 3 to 6 days after randomization according to institutional standards.7
- All 208 patients randomized to the CARVYKTI arm underwent apheresis and received bridging therapy with either DPd (n=182) or PVd (n=26). A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population).5
- Please see below for eligibility criteria for apheresis from the CARTITUDE-4 study protocol.7
- Patients randomized to the CARVYKTI arm underwent apheresis to acquire PBMCs 3 to 6 days after randomization according to institutional standards.7
PRODUCT LABELING
- CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
- DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
Clinical Data - cartitude-1 - phase 1b/2 study
Study Design/Methods
- Study enrollment was defined at the day of apheresis. Enrolled patients underwent apheresis to acquire PBMCs.3
- Patients' blood was apheresed according to institutional standards, with a collection target of 6×109 PBMC (range 2×109–20×109). Two apheresis collections may have been performed to attain this target.1
- CARVYKTI was manufactured from the patients T cells selected from the apheresis product.3
- Re-apheresis was permitted for patients whom apheresis or manufacturing failed. Patients were withdrawn from the study if unable to manufacture CARVYKTI after 2 apheresis attempts.3
- All patients that were enrolled in CARTITUDE-1 (N=113) underwent apheresis. A total of 101 patients were lymphodepleted, and 97 patients were treated with CARVYKTI.1
Patients had to meet the following criteria to proceed with apheresis:
- Clinical laboratory values required for enrollment (resulted within 24-hours prior to apheresis) are presented in Table: CARTITUDE-1: Clinical Laboratory Values Required for Enrollment.3
- No plasma cell leukemia at the time of apheresis (>2.0x109/L plasma cells by standard differential).3
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.3
- Negative pregnancy test for women of childbearing potential up to 72 hours prior to apheresis.3
- No antitumor therapy before apheresis as follows3:
- Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least
5 half-lives, whichever is less. - Monoclonal antibody treatment for multiple myeloma within 21 days.
- Cytotoxic therapy within 14 days.
- Proteasome inhibitor within 14 days.
- Immunomodulatory agent within 7 days.
- Radiotherapy within 14 days. However, if radiation portal covered ≤5% of the bone marrow reserve, the patient is eligible irrespective of the end date of radiotherapy.
- Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least
- Cumulative dose of corticosteroids should not exceed equivalent to ≥70 mg prednisone within the 7 days prior to the first dose of conditioning regimen.3
- As part of the study exclusion criteria, patients were excluded if they received a cumulative dose of corticosteroids equivalent to ≥ 70 mg of prednisone within the 7 days prior to apheresis.3
- No evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection. Patients on anti-infective agents within 7 days prior to apheresis must have received approval to proceed.3
- No major surgery ≤2 weeks prior to apheresis.3
- No live, attenuated vaccines ≤4 weeks prior to apheresis.3
- No supplemental oxygen use to maintain adequate oxygenation.3
- No new arrhythmia or other cardiac adverse events unless controlled with medical management and approved by the medical monitor.3
| Hematology | |
|---|---|
| Hemoglobin | ≥8.0 g/dL (≥5 mmol/L) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)a |
| Platelets | ≥50.0 x 109/L (must be without transfusion support in the 7 days prior to the laboratory test) |
| Lymphocyte count | ≥0.3 x 109/L |
| ANC | ≥0.75×109/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) |
| Chemistry | |
| AST and ALT | ≤3.0 × ULN |
| Creatinine Clearance | ≥40 mL/min/1.73 m2 |
| Total bilirubin | ≤2.0 × ULN; except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 × ULN is required) |
| Corrected serum calcium | ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L) |
| Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; MDRD, Modified Diet in Renal Disease; RBC, red blood cell; ULN, upper limit of normal.aFor patients who meet the inclusion criteria at screening, transfusion of RBCs is permitted after screening as needed to maintain a hemoglobin level ≥8.0 g/dL.bMDRD Formula:For serum creatinine in mg/dL, the eGFR for the MDRD formula is:eGFR (MDRD) mL/min per 1.73m2 = 175 x [serum creatinine (mg⁄dL)]-1.154 | |
CARTITUDE-1 Study Protocol - Re-Apheresis
- If patients required a repeat apheresis, additional screening assessments were to be collected before the second apheresis including: weight, hematology laboratory assessments, chemistry laboratory assessments, and echocardiogram or multiple-gated acquisition (MUGA) (if clinically indicated).3
- If the second apheresis fell outside of the 28-day window, all screening assessments (except bone marrow collection) were to be repeated.3
Clinical data - CARTITUDE-4 - phase 3 study
Study Design/Methods
- Patients randomized to the CARVYKTI arm underwent apheresis to acquire PBMCs.7
- Apheresis should have started 3 to 6 days after randomization and should have been performed according to institutional standards.7
- If for logistical reasons apheresis could not be performed 3 to 6 days after randomization, shorter timeframe was accepted when possible.7
- If aphesis was delayed after randomization, the sponsor should have been notified.7
- Patients in the CARVYKTI arm for whom apheresis or manufacturing failed may have been allowed additional attempts at apheresis or manufacturing and may have been allowed additional bridging therapy following discussion with the sponsor.7
- All 208 patients randomized to the CARVYKTI arm underwent apheresis and received bridging therapy with either DPd (n=182) or PVd (n=26). A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population).5
- The median time from apheresis material receipt to product release was 44 days (range, 25-127) and the median time from first apheresis to CARVYKTI infusion was 79 days (range, 45-246).5,8
The investigator should have contacted the sponsor if evidence of rapid disease progression or suspected central nervous system (CNS) involvement was observed between randomization and apheresis. Patients had to meet the following criteria to proceed with apheresis 7:
- Clinical laboratory values required for enrollment (resulted within 24-hours prior to apheresis) are presented in Table: CARTITUDE-4: Clinical Laboratory Values Required for Enrollment.7
- Hemoglobin ≥8 g/dL (packed red blood cell [PRBC] transfusion is permitted).7
- Platelet count >50 x 109/L (platelet transfusion is permitted).7
- Negative pregnancy test for women of childbearing potential up to 72 hours prior to apheresis.7
- No use of supplemental oxygen maintain adequate oxygenation.7
- ECOG performance status grade of 0 or 1.7
- No antitumor therapy before apheresis as follows7:
- Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less.
- Investigational vaccine within 4 weeks.
- Monoclonal antibody treatment within 21 days.
- Cytotoxic therapy within 14 days.
- Proteasome inhibitor therapy within 14 days.
- Immunomodulatory agent therapy within 7 days.
- Focal radiotherapy within 14 days. However, if the radiation is given for palliative purposes and the radiation portal covered ≤5% of the bone marrow reserve, the patient is eligible irrespective of the end date of radiotherapy. Radiotherapy within 14 days on measurable extramedullary plasmacytoma(s) is not permitted even in the setting of palliation for symptomatic management.
- No evidence of serious active viral, bacterial or uncontrolled systemic fungal infection. Patients on anti-infective agents within 7 days prior to apheresis must have received approval from sponsor to proceed.7
- No major surgery within 2 weeks before randomization or has not fully recovered from an earlier surgery, or has major surgery planned during the time the subject is expected to participate in the study (note: kyphoplasty or vertebroplasty are not considered major surgery). If there is a question about whether a procedure is considered a major surgery, the investigator must consult with the sponsor and resolve any issues before enrolling a patient in the study.7
- No live, attenuated vaccines within 6 weeks prior to randomization.7
- No new arrhythmia or other cardiac adverse events, uncontrolled with medical management and approved by the medical monitor.7
| Hematology | |
|---|---|
| Hemoglobin | ≥8.0 g/dL (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted) |
| Platelets | ≥75.0 x 109/L (without prior platelet transfusion within 7 days before the laboratory test) in patients in whom <50% of bone marrow nucleated cells are plasma cells; platelet count ≥50 x 109/L (without prior platelet transfusion within 7 days before the laboratory test) in patients in whom ≥50% of bone marrow nucleated cells are plasma cells |
| Lymphocyte count | ≥0.3 x 109/L |
| ANC | ≥1×109/L (without recombinant human G-CSF within 7 days and without pegylated G-CSF within 14 days of the laboratory test). |
| Chemistry | |
| AST and ALT | ≤3.0 × ULN |
| eGFR | ≥40 mL/min/1.73 m2 based upon MDRD formula calculationa. |
| Total bilirubin | ≤2.0 × ULN; except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 × ULN is required) |
| Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; G-CSF, granulocyte colony-stimulating factor; MDRD, Modified Diet in Renal Disease; RBC, red blood cell; ULN, upper limit of normal.aMDRD Formula:For serum creatinine in mg/dL, the eGFR for the MDRD formula is:eGFR (MDRD) mL/min per 1.73m2 = 175 x [serum creatinine (mg⁄dL)]-1.154 x [age]-0.203 x [1.212 if black] x [0.742 if female]For serum creatinine in µmol/L, the eGFR for the MDRD formula is:eGFR (MDRD) mL/min per 1.73m2 = 175 x [serum creatinine (μmol/L)/88.4]-1.154 x [age]-0.203 x [1.212 if black] x [0.742 if female] | |
CARTITUDE-4 Study Protocol - Re-apheresis
- For patients who require a repeat apheresis, the following assessments should be collected before the second apheresis: weight, hematology laboratory assessments, chemistry laboratory assessments and echocardiogram or MUGA (if clinically indicated). Blood samples for biomarker assessments including immunophenotyping and cytometry by time of flight (CyTOF)/PBMC (T-cell Receptor Sequencing [TCR Seq]/Plasma) should also be collected.7
LITERATURE SEARCH
A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 24 January 2025.
References
| 1 | Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. |
| 2 | |
| 3 | |
| 4 | |
| 5 | |
| 6 | |
| 7 | |
| 8 |