-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
B cell maturation antigen (BCMA) is mainly expressed on the surface of plasma cells and is a promising target
for the treatment of multiple myeloma (MM).
Several therapies currently being investigated or approved for MM that specifically target BCMA-expressing cells include bispecific antibodies (BsAbs), antibody drug conjugates (ADCs), and chimeric antigen receptor (CAR)-T cell therapies
.
Recent studies of anti-BCMA BsAbs and anti-BCMA ADCs suggest that patients with MM may still have disease progression despite these therapies and seek other treatments
.
Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy
that targets BCMA.
Preliminary results from the Phase I.
B/II, SINGLE-ARM CARTITUDE-1 CLINICAL TRIAL SUGGEST THAT CILTA-CEL PRODUCES EARLY, DEEP, AND DURABLE REMISSION IN PATIENTS WITH RELAPSED OR REFRACTORY
MM (RRMMM) WHO RECEIVE MULTIPLE LINES.
HOWEVER, THE CARTITUDE-1 STUDY, AS WELL AS MOST CLINICAL TRIALS TARGETING BCMA FOR MM, EXCLUDED PATIENTS
WHO HAD PREVIOUSLY RECEIVED TARGETED BCMA THERAPY.
The CARTITUDE-2 trial is a phase II, multi-cohort, open-label study evaluating the safety and efficacy
of cilta-cel in multiple patient populations.
Here, the investigators report initial results for cohort C, which includes RRMM patients
who have been previously exposed to targeted BCMA drugs.
Cohort C in the CARTITUDE-2 trial included RRMM patients who had previously received BCMA-targeted therapy (excluding cellular immunotherapy) to evaluate the efficacy and safety
of cilta-cel in these patients 。 The main inclusion criteria were: patient aged ≥ 18 years, diagnosed with MM according to International Myeloma Working Group (IMWG) diagnostic criteria, evidence of disease progression (PD) within 12 months of their end-line therapy (LOT) or within 6 months of previous treatment, resistance to their recent LOT, measurable disease at baseline, and European Collaborative on Oncology (ECOG) performance status score of 0 or 1
.
Patients must have previously received proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies (mAbs), and noncellular therapy targeted BCMA (ADC or BsAb monotherapy).
Patients received a single cilta-cel infusion (target dose 0.
75×106 CAR-positivelive T cells/kg) 5-7 days after detoxification pretreatment; Target range 0.
5-1.
0 ×106CAR-positive live T cells/kg).
The primary endpoint was minimal residual disease (MRD) negative (10-5) as defined by IMWG criteria, which was centrally assessed
by next-generation sequencing (NGS).
If the assessment is negative after 1 baseline ≥, the patient is considered MRD-negative
.
Secondary endpoints were incidence and severity of adverse events (AEs), overall response rate (ORR), very good partial response (VGPR) rate, complete response (CR) rate, and strict CR (sCR) rate based on IMWG response criteria, duration of response (DOR), and time
to response.
The exploratory endpoint was progression-free survival (PFS).
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) are graded
according to American Society of Transplantation and Cell Therapy standards.
patients and treatment
As of the data deadline of October 08, 2021, a total of 24 patients in Cohort C were enrolled and receiving treatment, of which 20 patients were treated
with cilta-cel.
Recent targeted BCMA drug therapies are BsAb (n=7, 35%) and ADC (n=13, 65%) (see Table 1).
The duration of prior targeted BCMA therapy ranged from 1 to 527 days, from the last targeted BCMA administration to apheresis from 26 to 895 days, and from the last targeted BCMA administration to cilta-cel infusion ranged from 62 to 944 days (see Table 2 for details).
At baseline, the median age of patients in Cohort C was 63 years (range: 44-81 years), 12 (60%) were male, and 19 (95%) were white
.
At screening, 5 patients (25%) had extramedullary disease and 3 patients (15%) had high-risk cytogenetics
.
Table 1: Baseline characteristics of patients
Table 2: Time to targeted BCMA therapy
Patient efficacy
Overall cohort efficacy
At the time of data cut-off, 13/20 patients (9 in the ADC group and 4 in the BsAb group) were still enrolled in the study (Figure 1).
At a median follow-up of 11.
3 months, patients had a negative MRD rate of 35% (95% CI, 15.
4-59.
2%)
at any time.
The ORR for all patients in Cohort C was 60.
0% (95% CI, 36.
1-80.
9%), the ≥ VGPR rate was 55%, and the ≥ CR rate was 30% (Table 3).
All 3 high-risk cytogenetics patients (all del17p) achieved ≥ VGPR
.
The median time to first response was 0.
95 months and to optimal response 2.
22 months (Table 3; Figure 2A).
The median DOR was 11.
5 months, the median PFS was 9.
1 months, and the PFS rate at 12 months was 38.
9% (95% CI, 16.
3-61.
1%; Figure 3A).
Of the 5 patients with extramedullary plasmacytoma at baseline, 4 patients achieved complete remission
of extramedullary plasmacytoma after CILTA-Cel treatment.
Figure 1: Study flowchart
Table 3: Efficacy of CILTA-Cel
Efficacy in patients targeting BCMA ADC exposure groups
Patients previously exposed to targeted BCMA ADCs had a median follow-up of 11.
8 months
after cilta-cel infusion.
Five patients achieved MRD-negative, and all 13 patients with targeted BCMA ADC exposure had a MRD-negative rate of 39% (95% CI 13.
9-68.
4%), an ORR of 61.
5% (95% CI: 31.
6-86.
1%), a median time to first response of 0.
97 months, and a median time to optimal response of 2.
58 months (Table 3; Figure 2B).
The median DOR was 11.
5 months and the median PFS was 9.
5 months (Figure 3B).Efficacy in patients targeting BCMA BsAb exposure groups
Patients previously exposed to targeted BsAbs had a median follow-up of 10.
9 months
after cilta-cel infusion.
2/7 patients were MRD-negative (2/3 patients were considered only evaluable patients).
The patient ORR was 57.
1% (95% CI: 18.
4 to 90.
1%), with a median time to first response of 0.
92 months and a median time to optimal response of 1.
4 months (Table 3; Figure 2C).
The median DOR was 8.
2 months and the median PFS was 5.
3 months (Figure 3C).
Figure 2: Response of
patients receiving CILTA-CEL treatment.
Remission in treatment-responsive patients (A) and in all patients previously exposed to ADC(B) or BsAb(C).
Figure 3: Patient PFS
.
PFS for the overall cohort (A), ADC-exposed patients (B), and BsAb-exposed patients (C).
Factors associated with response to treatment
The median duration of exposure to prior targeted BCMA therapy in patients in response was shorter than that in patients who did not respond, at 29.
5 and 63.
5 days
, respectively.
The median time between the last targeted BCMA drug therapy and apheresis was shorter in the cilta-cel responder (56.
5 days and 117.
5 days, respectively), and the median time between the last targeted BCMA drug treatment and the cilta-cel infusion was also shorter at 161.
0 days and 235.
0 days
, respectively, compared with no respondents.
Patient safety
All 20 patients experienced adverse events (TEAEs) during treatment after receiving cilta-cel treatment, of which 19 developed TEAE
associated with cilta-cel treatment.
Grade 3/4 AEs in > patient were predominantly cytopenias (neutropenia, n=17; thrombocytopenia, n=14; anemia, n=11; leukopenia, n=11; lymphopenia, n=6), but also hypocalcemia (n=2), hypophosphatemia (n=4), hypokalemia (n=2), and ICANS (n=2) (Table 4).
Table 4: Patient AE occurrence
Pharmacokinetics
The pharmacokinetic characteristics of Cilta-cel are CAR transgene levels and CAR-positive cells
in peripheral blood and bone marrow.
After infusion, the CAR transgene has an initial amplification phase with a peak time of approximately 15 days (range: 9-41 days), followed by a rapid decline followed by a slow decline
over several months.
The median time to the last measurable CAR transgene was approximately 127 days (range: 15-213).
Patients with RRMM who have received multiple prior lines and have been previously exposed to non-cellular therapies targeted for BCMA respond to cilta-cel with an ORR of 60%.
Preliminary results from this study cohort C, along with continued follow-up, inform the sequence of administration of drugs that target BCMA to maximize
patient benefit.
References
Adam D Cohen , Maria-Victoria Mateos , Yael C Cohen,et al.
Efficacy and safety of cilta-cel in patients with progressive MM after exposure to other BCMA-targeting agents.
Blood.
2022 Sep 12; blood.
2022015526.
Disclaimer: This platform aims to deliver more medical information
to healthcare professionals.
The content published on this platform cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice
.
If such information is used for purposes other than understanding medical information, this platform does not assume relevant responsibilities
.
The content published by this platform does not mean that it agrees with its description and views
.
If copyright issues are involved, please contact us and we will deal with it
as soon as possible.
Poke "Read Original" to see more
