Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and ...efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma.
Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE; CRS and ICANS by ASTCT).
As of the February 2021 data cutoff (median follow-up: 5.8 months 2.5–9.8), 20 patients (65% male; median age 60 years 38–75) received cilta-cel; 1 patient was treated in an outpatient setting. Patients (n = 12: <3 prior LOT; n = 8: 3 prior LOT) received a median of 2 (1–3) prior LOT. All patients were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT; 40% were triple-class refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3); median time to best response was 1.9 month (0.9–5.1). Median duration of response was not reached. All patients (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; grade 3/4: 90%), thrombocytopenia (80%; grade 3/4: 35%), anemia (65%; grade 3/4: 40%), lymphopenia (60%; grade 3/4: 55%), and leukopenia (55%; all grade 3/4). 85% of patients had CRS; 10% were grade 3/4. Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of patients (all grade 1/2). Three patients had ICANS (n = 1: grade 1; n = 2: grade 2); median time to onset was 8 days (7–11) and median duration was 2 days (1–2). One patient had grade 2 facial paralysis; time to onset was 29 days with a duration of 51 days. One death occurred due to Covid-19 (assessed as treatment-related by investigator). The safety profile was manageable in the patient who was treated in an outpatient setting.
Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.
A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in patients with MM who had 1–3 prior LOT.
Analysing osteolytic and osteoblastic bone lesions in systematically affected skeletons, e.g. in multiple myeloma or bone metastasis, is a complex task. Quantification of the degree of bone ...destruction needs segmentation of all lesions but cannot be managed manually. Automatic bone lesion detection is necessary. Our future objective is comparing modified bones with healthy shape models. For applying model based strategies successfully, identification and position information of single bones is necessary. A solution to these requirements based on bone medullary cavities is presented in this paper. Medullary cavities are useful for shape model positioning since they have similar position and orientation as the bone itself but can be separated more easily. Skeleton segmentation is done by simple thresholding. Inside the skeleton medullary cavities are segmented by a flood filling algorithm. The filled regions are considered as medullary cavity objects. To provide automatic shape model selection, medullary cavity objects are assigned to bone structures with pattern recognition. To get a good starting position for shape models, principal component analysis of medullary cavities is performed. Bone identification was tested on 14 whole-body low-dose CT scans of multiple myeloma patients. Random forest classification assigns medullary cavities of long bones to the corresponding bone (overall accuracy 90%). Centroid and first principal component of medullary cavity are sufficiently similar to those of bone (mean centroid difference 21.7 mm, mean difference angle 1.54° for all long bones of one example patient) and therefore suitable for shape model initialization. This method enables locating long bone structures in whole-body CT scans and provides useful information for a reasonable shape model initialization.
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