March 2022: CAR-T therapy, CAR-T technology, what are CAR-T cell immunotherapy ? CAR-T treatment price, cost, the latest CAR-T clinical trial recruitment information summary.
The concept of boron neutron capture therapy has been proposed for decades, but it was not until last year that it really became popular among patients and became a hot spot; the antibody-drug conjugate (ADC), known as a “biomissile”, finally became popular last year. The research on CAR-T cell therapy has also gone through many years, but since last year, especially since the second half of last year, a large number of CAR-T therapies have been “combined.”. Anti-cancer “new forces” are rapidly emerging.
Emily Whitehead, the first child with leukemia treated with CAR-T therapy and the “spokesperson” of CAR-T therapy, has defeated leukemia for nearly ten years. Now this “miracle” therapy has finally come to her around our patients.
From 2021 to the present, CAR-T therapy has shown a trend of accumulation, and many products have been launched one after another. During this period, my country has ushered in 3 CAR-T therapies successively, allowing patients to see the dawn of a new program.
Liso-Cel
(Lisocabtagene maraleucel, Breyanzi)
Status: Approved for marketing (FDA)
When: February 6, 2021
Introduction: Liso-Cel is an anti-CD19 therapy based on a patient’s own T cells.
Indications: Large B-cell lymphoma (adult patients with some types of large B-cell lymphoma who have not responded to at least 2 other types of systemic therapy or have relapsed after therapy)
Relevant clinical trials and data:
[TRANSCEND NHL 001 trial (NCT02631044)] For patients treated with Liso-Cel, the overall remission rate was 73%, of which the complete remission rate was as high as 53%; patients could achieve the first remission or partial remission after about 1 month of treatment.
At a median follow-up of 12 months, 54.7% of patients remained in clinical remission; patients had a median progression-free survival of 6.8 months and a median overall survival of 21.1 months; patients had a 1-year survival rate of 58% .
Axi-Cel
(Axicabtagene ciloleucel, Yescarta)
Status: Approved for marketing (FDA)
When: March 5, 2021
Introduction: The FDA has granted Yescarta, a CAR-CD19 T cell therapy, breakthrough therapy designation and priority review for the indication of follicular lymphoma. The FDA has previously approved Yescarta’s indication for large B-cell lymphoma. After this approval, Yescarta became the first CAR-T cell immunotherapy for follicular lymphoma.
Indications: Follicular lymphoma (relapsed or refractory follicular lymphoma, adult patients, after two or more systemic therapies)
Relevant clinical trials and data:
[ZUMA-5 trial] The overall response rate reached 91%, and the complete response rate was as high as 60%; the median duration of response was not reached at a median follow-up of 14.5 months, and 74% of patients had a response duration of more than 18 months.
Status: Approved for Marketing (FDA, Supplemental Biologics License)
Indication: High-dose regimen for second-line treatment of adult patients with relapsed/refractory B-cell lymphoma
Ide-cel
(Idecabtagene vicleucel, Abecma)
Status: Approved for marketing (FDA)
When: March 26, 2021
Introduction: Abecma is a BCMA-directed autologous chimeric antigen receptor (CAR) T cell therapy customized from the patient’s autologous T cells.
Indications: Multiple myeloma (adult patients with relapsed or refractory multiple myeloma who have received 4 or more lines of therapy, including immunomodulators, proteasome inhibitors and CD38 monoclonal antibodies)
Relevant clinical trials and data:
[Multi-center study] The overall remission rate of all patients was 72%, of which the complete remission rate was 28%; among the patients who achieved clinical complete remission, 65% of the patients had remission that lasted for more than 12 months.
KTE-X19
(Brexucabtagene Autoleucel, Tecartus)
Status: Approved for marketing (FDA)
When: October 1, 2021
Introduction: A CAR-CD19 T cell therapy previously approved for the treatment of mantle cell lymphoma.
Indications: B lymphocytic leukemia (adult patients with relapsed and refractory B lymphocytic leukemia)
Relevant clinical trials and data:
[ZUMA-3 trial] The complete remission rate was 56.4%, and 14.5% of patients achieved clinical complete remission. Only the blood counts did not return to normal, that is, CRi was achieved; the median progression-free survival was 11.6 months, and the median overall survival was 18.2 months. Patients who achieved clinical complete remission (including blood counts that did not return to normal) had a median progression-free survival of 14.2 months and had the shortest overall survival of 16.2 months; for those who did not, the median overall survival was only 2.4 months..
Yijililenxe Injection
(Aquilon Race; Yescarta, Axicabtagene Ciloleucel, Axi-Cel; FKC876)
Status: Approved for Marketing (NMPA)
When: June 23, 2021
Price: 190,000 USD
Introduction: The first CAR-T cell product launched in China is CAR-CD19-T cell therapy.
Significance: For adults with relapsed or refractory large B-cell lymphoma after receiving second-line or above standard therapy, this medicine is indicated. It can be used for diffuse large B-cell lymphoma unspecified, primary mediastinal B-cell carcinoma lymphoma tumor, high-grade B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma.
Relevant clinical trials and data: [ZUMA-5 trial] The overall response rate reached 91%, and the complete response rate was as high as 60%; the median duration of response was not reached at a median follow-up of 14.5 months, and 74% of patients had a response duration of more than 18 months.
Ruiki Orenza Injection
(Relma-cel, JWCAR029)
Status: Approved for Marketing (NMPA)
When: September 3, 2021
Price: 200,000 USD
Introduction: The second CAR-T cell product launched in China, and also the first domestic CAR-CD19-T therapy officially approved for marketing, was developed by Shanghai WuXi Junuo.
Indications: Large B-cell lymphoma (adult patients with relapsed or refractory large B-cell lymphoma after second-line or above systemic therapy)
Relevant clinical trials and data:
The overall response rate was 60.3%.
Sidaki Aurexa Injection
(LCAR-B38M, JNJ-4528, Cilta-cel, Carvykti)
Status: Approved for Marketing (NMPA)
When: February 28, 2022
Price: US$465,000/needle
Introduction: The third CAR-T cell product launched in China is a CAR-BCMA-T therapy jointly developed by Janssen and Legend Bio.
Indications: Multiple myeloma (adult patients with relapsed/refractory multiple myeloma. Relevant clinical trials and data:
The overall response rate was 98%, of which 83% of patients achieved a strict complete response; the 18-month progression-free survival rate was 66%, and the 2-year progression-free survival rate was 61%; the 18-month overall survival rate was 81 %, and the 2-year overall survival rate was 74%.
In addition to the above listed products, there are more CAR-T cell products that are in the pre-market stage, gradually accumulating clinical trial data, or have submitted a marketing application, and are only a step away from officially meeting patients.
Among them, there are many “rookies” with potential as much as the marketed products, and during this period they have obtained various FDA licenses or “titles,” such as orphan drug designation, fast track qualification, advanced regenerative immune therapy, and so on.
Cilta-cel
(Ciltacabtagene autoleucel, domestic name: Ciltacabtagene autoleucel injection)
Status: (FDA) Priority Review
Indications: Multiple myeloma (relapsed/refractory multiple myeloma)
Introduction: CAR-BCMA-T Cell Therapy
Relevant clinical trials and data:
[CARTITUDE-1 trial] The overall response rate was 98%, of which 83% of patients achieved a strict complete response; the 18-month progression-free survival rate was 66%, and the 2-year progression-free survival rate was 61%; the 18-month overall survival rate was 81 %, and the 2-year overall survival rate was 74%.
ALLO-715
Status: (FDA) RMAT Designation, Orphan Drug Designation
Indications: Multiple myeloma (relapsed/refractory multiple myeloma)
Introduction: CAR-BCMA-T Cell Therapy
Relevant clinical trials and data:
UNIVERSAL trial: In patients who received 3.2×10^6 (320 million) CAR-T cell infusions, the overall response rate reached 60%. The median number of treatment lines for patients was 5.
Kymriah
(Tisagenlecleucel)
Status: (FDA) Priority Review for New Indications
Indications: follicular lymphoma (second-line or above treatment of relapsed or refractory follicular lymphoma)
Introduction: CAR-CD19-T cell therapy, approved for adult patients with relapsed/refractory large B-cell lymphoma
Relevant clinical trials and data:
[JULIET trial] The overall remission rate of 613 patients was 57.4%, of which 42.4% were in complete remission.
CTX110
Status: (FDA) RMAT designation
Indications: B-cell malignancies (relapsed or refractory CD19-positive B-cell malignancies)
Introduction: Allogeneic CAR-CD19-T Cell Therapy
Relevant clinical trials and data:
[CARBON Trial] Among 24 patients who met the intention-to-treat criteria, the overall response rate of CTX110 in the second dose group was 58%, including 38% of patients who achieved a clinically complete response.
CT120
Status: (FDA) Orphan Drug Designation
Indication: acute lymphoblastic leukemia
Introduction: CD19/CD22 Dual Targeting Chimeric Antigen Receptor (CAR) T Cell Therapy
C-CAR039
Status: (FDA) RMAT Designation, Fast Track
Indications: Diffuse large B-cell lymphoma
Introduction: CD19/CD20 Dual Targeting Chimeric Antigen Receptor-T Cell Therapy
Relevant clinical trials and data:
【Phase I trial】The overall response rate of patients with relapsed or refractory diffuse large B-cell lymphoma was 91.7%, of which the complete response rate was 83.3%.
CT103A
Status: (FDA) Orphan Drug Designation
Indication: multiple myeloma
Introduction: CAR-BCMA-T Cell Therapy
Relevant clinical trials and data:
[Phase I trial] Among 18 patients with relapsed and/or refractory multiple myeloma, the overall response rate of CT103A was 100%, of which 72.2% of the patients reached the standard of complete response; the 1-year progression-free survival rate was 58.3 %.
Liso-Cel
(Lisocabtagene maraleucel, Breyanzi)
Status: (FDA) Priority Review, has accepted the application for marketing approval
Introduction: CAR-CD19-T Cell Therapy
Indication: Large B-cell lymphoma (adult patients with relapsed or refractory large B-cell lymphoma who have failed first-line therapy)
So far, all CAR-T cell therapies that have been marketed have targeted various types of hematological tumors. Even if promising therapies are included, there are very few projects targeting solid tumors. It is so difficult for CAR-T therapy to break through solid tumors, and only a few “elites” can be on this most difficult “battlefield.”.
CT041
Status: (FDA) RMAT Designation, Orphan Drug Designation
Indications: Gastric cancer (Claudin18.2 positive advanced gastric cancer and gastroesophageal junction adenocarcinoma)
Introduction: CAR-Claudin 18.2-T Cell Therapy
Relevant clinical trials and data:
The overall response rate of all patients was 48.6%, and the disease control rate was 73%; the overall response rate of all gastric cancer patients was 57.1%. The overall response rate of gastric cancer patients who had failed at least 2 lines of therapy in the past was 61.1%, and the disease control rate was 83.3%.
There is no doubt that CT041 is one of the most advanced and effective regimens among all CAR-T cell therapies for solid tumors. At present, this program is still recruiting subjects, and patients who have the opportunity to try it must not miss it!
AIC100
Status: (FDA) Fast Track
Indications: Thyroid cancer (anaplastic thyroid cancer and refractory, poorly differentiated thyroid cancer)
Introduction: CAR-ICAM-1-T Cell Therapy
There are three CAR-T products currently listed in China: one is 1.2 million per injection, the other is 1.29 million per injection, and the third is US$465,000 per injection. For the vast majority of patients, i’s an unbearable price.
The cost of CAR-T therapy is obviously expensive, but at the same time, my country is the country with the largest number of CAR-T cell therapy research and clinical trials, and a large number of domestic centers are recruiting Chinese patients for trial projects. For patients who meet the needs of the indication, this is a good channel to enjoy new drug treatments in advance and avoid huge expenses.
