A newer report of this study has been published: Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (2024)
Ide-cel is the first CAR-T therapy approved for myeloma. In this study, patients whose disease had come back after 2 to 4 earlier treatments stayed free of disease progression on average about three times longer with ide-cel (13 months versus 4 months), and nearly 4 out of 10 reached a complete response. Fever and low blood pressure caused by an immune reaction (CRS) were very common but usually mild.
Relapsed or refractory multiple myeloma after 2 or more lines of therapy including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lymphodepletion | |||
| Cyclophosphamide + fludarabine | Cyclophosphamide 300 mg/m² + fludarabine 30 mg/m² | IV | 3 days |
| Single infusion | |||
| Idecabtagene vicleucel | 300 to 510 × 10⁶ CAR-positive T cells | IV | 2 days after completion of lymphodepletion |
Ensure tocilizumab is available.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Leukapheresis; up to 1 cycle of bridging therapy (DPd, DVd, IRd, Kd or EPd; the same standard regimen assigned to the patient before randomisation) from leukapheresis until 14 days before lymphodepletion; then cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² as IV infusions daily for 3 days, starting 5 days before infusion; and a single infusion of idecabtagene vicleucel: target dose range 150 × 106 to 450 × 106 CAR-positive T cells (abstract and ClinicalTrials.gov); permitted range 150 to 540 × 106 and median dose received 445.3 × 106 (range 174.9 to 529.0 × 106) cells (SmPC). Of 254 patients, 249 underwent leukapheresis and 225 (88.6%) received ide-cel; 192 of them (85.3%) had bridging therapy.
One of five standard regimens, assigned before randomisation on the basis of the patient's most recent antimyeloma treatment: daratumumab–pomalidomide–low-dose dexamethasone (DPd), daratumumab–bortezomib–low-dose dexamethasone (DVd), ixazomib–lenalidomide–low-dose dexamethasone (IRd), carfilzomib–low-dose dexamethasone (Kd) or elotuzumab–pomalidomide–low-dose dexamethasone (EPd). The dose and schedule of each regimen are not given in the abstract, the ClinicalTrials.gov record, the FDA label or the SmPC, and the full text was not available to us. 126 of 132 patients were treated; after confirmed progression, ide-cel was allowed (60 patients received it).
Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT03651128 (target dose range); EMA SmPC for Abecma (section 5.1) and its FDA label (lymphodepletion, bridging therapy, permitted range and dose received); doses of the standard regimens are not given in the available sources
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Adults with relapsed and refractory multiple myeloma who had received two to four prior regimens (including immunomodulatory drugs, proteasome inhibitors and daratumumab) and were refractory to the last regimen. 66% were triple-class refractory and 95% daratumumab-refractory. Response (minimal response or better) to at least one prior regimen and ECOG 0 or 1 were required; CNS involvement or a history of CNS disorder, prior allogeneic transplant, prior investigational gene or cell therapy or prior BCMA-targeted therapy, creatinine clearance less than 45 mL/min, AST or ALT more than 2.5 times the upper limit of normal and LVEF less than 45% were exclusion criteria (SmPC).
Primary endpoint: progression-free survival.
Key secondary endpoints: overall response (partial response or better) and overall survival; safety.
Grade 3 or 4 adverse events: 93% with ide-cel versus 75% with standard regimens. Among 225 patients who received ide-cel: cytokine release syndrome 88% (grade 3 or higher: 5%) and investigator-identified neurotoxicity 15% (grade 3 or higher: 3%).
Based on this study, in April 2024 the FDA extended the indication of ide-cel (Abecma) to patients after two or more prior lines of therapy (including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody). Together with CARTITUDE-4, this study brought anti-BCMA CAR-T into earlier lines of treatment for relapsed myeloma.
The study was open-label and patients in the standard group could receive ide-cel after progression, which complicates the overall survival analysis. Overall survival data in this report were immature, and early deaths in the ide-cel group (before receiving it or after infusion) were reported. Not all patients randomised to ide-cel received it (225 of 254).
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
Who are you reading this site as?
Your choice applies to every page; change it any time from the bottom of the page.
Type to search...