2021 IMW BCMA CAR-T therapy cilta-cel treatment of MM research results update

The 18th International Myeloma Symposium (IMW) in 2021 will be held simultaneously on September 8-11, 2021 in Vienna, Austria, and online.
The conference is hosted by the International Myeloma Society (IMS), dedicated to the promotion of multiple myeloma (MM) The latest breakthrough scientific and clinical communication with related plasma cell diseases
.

Ciltacabtagene autoleucel (cilta-cel) is a self-chimeric antigen receptor T cell (BCMA CAR-T) therapy targeting BCMA.
At this conference, CARTITUDE-1 and CARTITUDE for cilta-cel treatment of relapsed and refractory MM were announced.
-2 Research update results
.

The editor now organizes the main content of the research as follows for the reference of readers
.

Abstract number: OAB-024 Title: Treatment of relapsed and refractory MM with cilta-cel: The latest results of the CARTITUDE-1 study The phase Ib/II CARTITUDE-1 study explored the efficacy and safety of cilta-cel in the treatment of relapsed and refractory MM
.

The study included patients with relapsed and refractory MM who had previously received ≥3 treatment options (or double refractory to proteasome inhibitors and immunomodulators) and had received anti-CD38 monoclonal antibody therapy
.

The patient received lymphocytic depletion chemotherapy (cyclophosphamide 300mg/m2 daily, fludarabine 30mg/m2 for 3 days) 5-7 days later, and received cilta-cel infusion (target dose: 0.
75×106 CAR-T cells) /kg, range: 0.
5-1.
0×106 CAR-T cells/kg)
.

The main purpose of the study is to evaluate the safety of cilta-cel, determine the recommended phase II dose (phase Ib), and evaluate the efficacy (phase II)
.

 As of February 11, 2021, 97 patients (previous median 6-line treatment) have received cilta-cel treatment
.

The overall response rate (ORR) was 97.
9% (95%CI: 92.
7%-99.
7%), of which 80.
4% of patients achieved a strict complete response (sCR), and 94.
8% of patients achieved a very good partial response (VGPR) or Better state of relief
.

The median time to first remission was 1 month (range: 0.
9-10.
7), and the median time to complete remission (CR) or better remission was 2.
6 months (range: 0.
9-15.
2)
.

The median duration of remission was 21.
8 months (95%CI: 21.
8-NE)
.

61 patients with minimal residual disease (MRD) status can be assessed, of which 91.
8% of patients are MRD negative (10-5 level)
.

The 18-month progression-free survival (PFS) rate was 66% (95%CI: 54.
9%-75.
0%), and the 18-month overall survival (OS) rate was 80.
9% (95%CI: 71.
4%-87.
6%)
.

The median PFS of all patients was 22.
8 months (95%CI: 22.
8-NE), and the median PFS of patients who reached sCR did not reach
.

 Grade 3-4 hematological adverse events with an incidence of ≥20% include neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), lymphocytes Reduce symptoms (50%)
.

CRS occurred in 95% of patients (4% was grade 3-4), the median time of occurrence of CRS was 7 days (range: 1-12 days), and the median duration was 4 days (range: 1-14 days, except 1 patient lasted 97 days)
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Except for one patient with grade 5 CRS and hemophagocytic lymphohistiocytosis, CRS in all patients was relieved
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21% of patients had neurological toxicity (≥3 grade: 10%)
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Twenty-one patients died after receiving cilta-cel treatment.
No patient died 30 days after treatment, 2 patients died within 100 days after treatment, and 19 patients died after 100 days of treatment
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10 patients died of disease progression, 6 patients died of treatment-related events, and 5 patients died of treatment-unrelated events
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Research conclusions At a median follow-up of 18 months, cilta-cel achieved early, lasting and deep disease remission in patients with relapsed and refractory MM, and its safety was controllable
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Related research is currently exploring the feasibility of cilta-cel for early treatment of MM and outpatient treatment for MM
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Abstract number: OAB-023 Title: Efficacy and safety of cilta-cel in the treatment of relapsed and refractory MM: Initial results of the CARTITUDE-2 study The phase II CARTITUDE-2 study (NCT04133636) evaluated the efficacy and safety of cilta-cel in the treatment of MM.
At the same time, the feasibility of cilta-cel outpatient medication was explored
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Cohort A of this study included patients with MM who had undergone disease progression after receiving 1-3 line treatments (including proteasome inhibitors and immunomodulators).
The enrolled patients must be refractory to lenalidomide and have not received BCMA targeted drugs.
Treatment
.

The patient received lymphocytic depletion chemotherapy (cyclophosphamide 300mg/m2, fludarabine 30mg/m2 for 3 days) 5-7 days later, and received cilta-cel infusion (target dose: 0.
75×106 CAR-T cells/kg )
.

The primary endpoint of the study was MRD negative (10-5 level), and the secondary endpoints were remission rate and safety
.

 As of the data cutoff (February 2021), the median follow-up time was 5.
8 months (2.
5-9.
8)
.

Twenty patients received cilta-cel treatment, and one patient received treatment in the outpatient clinic
.

65% of patients were male, and the median age was 60 years (range: 38-75)
.

The number of previous treatment lines in the patients was 2 (range: 1-3), the number of previous treatment lines in 8 patients was 3, and the other 12 patients were all less than 3
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All patients have been treated with proteasome inhibitors, immunomodulators, and dexamethasone, 95% of patients have been treated with alkylating agents, and 65% of patients have been treated with daratumumab
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95% of patients are refractory to the last-line treatment, and 40% of patients are triple refractory
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 The ORR of cilta-cel treatment of patients with relapsed and refractory MM was 95% (95%CI: 75%-100%), 75% (95%CI: 51%-91%) of patients achieved CR/sCR, 85% (95% CI: 51%-91%) %CI: 62%-97%) of patients reached ≥VGPR
.

The median time to first remission was 1.
0 month (range: 0.
7-3.
3), the median time to best remission was 1.
9 months (range: 0.
9-5.
1), and the median duration of remission was not reached
.

The MRD status of 4 patients was detectable, and all 4 patients were MRD negative by the end of the data
.

 Hematological adverse events with an incidence of ≥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%), leukopenia (55%, all grades 3-4)
.

Cytokine Release Syndrome (CRS) (grade 3-4: 10%) occurred in 85% of patients.
The median time to onset of CRS was 7 days (range: 5-9), and the median duration was 3.
5 days (range: 2-11)
.

Twenty percent of patients developed neurotoxicity (all grades 1-2), and 3 patients (1 grade 1 and 2 grade 2) developed immune effector cell-related neurotoxicity syndrome (ICANS).
The median time to onset was the first 8 days (range: 7-11), median duration is 2 days (range: 1-2)
.

One patient developed grade 2 facial paralysis, the onset time was the 29th day, and the duration was 51 days
.

One patient died of COVID-19.
The investigator assessed that the death of this patient was related to cilta-cel treatment
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The safety of cilta-cel's outpatient treatment is controllable
.

Research conclusions Cilta-cel has achieved early and deep disease remission in MM patients with controllable safety
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Follow-up CARTITUDE-2 and CARTITUDE-4 studies will continue to explore the feasibility of cilta-cel outpatient treatment
.

References: 1.
AdamCohen, et al.
2021 IMW.
OAB-023.
2.
SundarJagannath, et al.
2021 IMW.
OAB-024.
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