JCO: Chen Saijuan's team at Shanghai Jiao Tong University found the newly developed CAR-T method effective in treating relapsed/refractory multiple myeloma

On October 21, 2022, 11 companies including Shanghai Jiao Tong University, Xi'an Jiaotong University, and Peking University joined forces, and Chen Saijuan was the corresponding author in the Journal of Clinical Oncology (IF=51) published online titled “Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor–T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1)", this pivotal Phase II open-label study (ClinicalTrials.
gov label: NCT03758417) Conducted at 8 trial sites in China, recruiting those who had previously received more than 3 drug treatments (including proteasome inhibitors and immunomodulatory drugs).
Adult patients with
RRMM.
This study found that a single injection of cilta-cel has a good risk-benefit relationship and can produce early, deep and durable responses
in a large number of pretreated RRMM patients in China.

In China, the morbidity and mortality of multiple tumors (MM) have increased, but the availability of new therapeutic drugs is limited and the clinical need remains unmet
.
In 2019, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD) refractory relapsed/refractory MM (RRMM) were targeted The patient's daratumumab monotherapy was approved by Chinese regulatory authorities with a total effective rate (ORR) of 29%.

In 2021, pomalidomide / dexamethasone and pomalidomide were approved on the basis of studies in patients exposed to > 2 previous therapeutic lines (LOT).
Carfilzomib/dexamethasone combination therapy
.
Efficacy is modest, with an ORR of 31% to 36% and median progression-free survival (mPFS) of approximately 4 to 6 months
.

Chimeric antigen receptor T cell (CAR-T) therapy uses modified autologous T cells that are activated when the target cells are contacted to kill malignant cells.

Several CAR-T therapies are being developed that target B cell maturation antigens (BCMA), which are selectively expressed
in plasma cells.
Ciltacabtagene autotoleucel (cilta-cel) is a CAR-T cell therapy that targets a domain by expressing two BCMA domains and a CD3z Signal domain
.

Flowchart (Image from Journal of Clinical Oncology).

Legend-2 is a Phase I, first-of-its-kind human study in China, which showed that LCAR-B38M produced a deep and durable response in patients with RRMM: at one study site (n= 57), ORR was 88%, 74% of patients achieved complete remission or better (≥CR), 68% Achieve a negative minimum residual disease (MRD); mPFS is 20 months
.
In the other three locus, 17 patients had an ORR of 88% and 76% achieved ≥ CR; The 12-month PFS was 53%.

Similarly, CARTITUDE-1, a Phase Ib/II study of cilta-cel conducted in the United States, had an ORR of 98%.
, 83% of patients achieved strict CR (sCR) (mPFS) and median overall survival [mOS] at a median 2-year follow-up )
。 CARTIFAN-1 is a pivotal study of CTA-cel in Chinese RRMM patients who have previously received > 3 times LOT (including PI and IMiD).

Here, the study reported preliminary efficacy and safety results
after a median follow-up of 18 months.

(A) Progression-free survival Kaplan-Meier curve and (B) Overall survival (Figure from Journal of Clinical Oncology).

This pivotal Phase II open-label study (ClinicalTrials.
gov label: NCT03758417) was conducted at 8 trial sites in China and recruited previously received Adult patients with RRMM with more than 3 drug treatments, including proteasome inhibitors and immunomodulatory drugs.

Patients receive a single CILTA-CEL infusion (target dose 0.
75 × 106 chimeric antigen receptor-positive live T cells/kg)
。 The primary endpoint is total effective rate
.
Secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs).

As of July 19, 2021, 48 patients have received the Cilta-Cel infusion
.
At a median follow-up of 18 months, the total response rate was 89.
6% (95% CI, 77.
3 to 96.
5), with a median duration of about one month; 77.
1% of patients (95% CI, 62.
7 to 88.
0) achieved a complete response or better
.
The median reaction duration, PFS, and OS were not reached
.
The PFS and OS rates at 18 months were 66.
8% (95% CI, 49.
4 ~ 79.
4) and 78.
7% (95% CI), respectively , 64.
0 ~ 88.
0)
。

Hematologic adverse effects are common and include anemia (100%), neutropenia (97.
9%), lymphopenia (95.
8%), and thrombocytopenia (87.
5%)
。 Cytokine release syndrome (35.
4% grade 3/4) occurred in 97.
9% of patients; The median time to onset was 7 days and the median duration was 5 days
.
Infection occurred in 85.
4% of patients (37.
5% grade 3/4).

Ten deaths occurred after cilta-cel infusion, eight of which were due to treatment-related AEs
.
In conclusion, these data suggest that a single injection of cilta-cel has a good risk-benefit relationship and can produce early, deep and durable responses
in a large number of pretreated RRMM patients in China.

Original source:

https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
00690