The 60th Annual Meeting of the American Society of Hematology (ASH) was held in San Diego, USA from December 1-4. This is the largest American medical conference on the latest developments in blood diseases. CAR-T cell therapy is an important research and development direction for the treatment of hematological cancer. This article sorts out the latest clinical data on CAR-T therapy published at the current ASH conference.

1. The objective remission rate of bb21217 in the treatment of relapsed/refractory multiple myeloma was 83%.

The bb21217, developed by Bluebird Bio and Celgene, is a new generation of CAR-T cell therapy that targets the B cell mature antigen (BCMA) antigen. Compared with the previous generation of CAR-T therapy, it increases the persistence of CAR-T cells in the human body, allowing these cells to last longer. Phase 1 clinical trial data for patients with relapsed/refractory multiple myeloma (MM) showed objective clinical remission in 83% (n=10) of the 12 patients who received bb21217. At the data collection deadline, 9 of the 10 responding patients were relieved, 3 of whom achieved complete remission (CR), 2 achieved very good partial remission, and 4 achieved partial remission.

At the same time, bb21217 therapy showed good safety and therapy for incremental dose testing was allowed.

2. Yescarta has a long-term total response rate of 83% in patients with refractory large B-cell lymphoma.

Yescarta of Kite, a subsidiary of Gilead Sciences, is the second FDA-approved CAR-T therapy. In a clinical trial called ZUMA-1, patients with refractory large B-cell lymphoma received a dose of Yescarta and followed up for at least two years. The results of the trial showed that after two years of treatment, the patient (n = 101) had a total response rate of 83% and a complete response rate of 58%. At a median follow-up of 27.1 months, 39% of patients treated remained responsive to therapy. Of the patients who responded to therapy 12 months after receiving therapy, 93% remained responsive to therapy after 24 months.

3. JCAR017 (lisocabtagene maraleucel) 1/2 stage clinical results are positive.

Celgene announced the clinical outcome of 1/2 phase of JCAR017 developed by its subsidiary Juno Therapeutics in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These patients have been treated with ibrutinib or venetoclax, but the symptoms continue to worsen. Interim results showed that among the 16 patients treated, the overall response rate was 81% and the complete response rate was 43%. Most patients who underwent minimal residual disease (MRD) testing had negative MRD levels.

4. The complete remission rate of Kymriah to treat acute lymphocytic leukemia can be as high as 82%.

Novartis' Kymriah is the first FDA-approved CAR-T therapy. At the ASH Annual Meeting, the company published long-term follow-up results for two clinical studies. In a study called ELIANA, Kymriah was used to treat adolescent patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Data analysis 24 months after treatment showed that in 79 patients, the complete response rate or complete remission plus partial blood count reduction rate reached 82% after 3 months of treatment. The recurrence-free survival rate was 62% at 24 months. The trial has not yet reached the median remission period.

In the JULIET study of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the overall response rate was 54% in patients with a median follow-up of 19 months (n=99). The complete response rate is 40%. The trial has not yet reached the median remission period. The patient's recurrence-free survival rate was 64% at 12 months and 18 months after treatment.

Introducing combination therapy into CAR-T cell therapy to improve response rate and reduce side effects.

The approval of CAR-T cell therapy offers new options for patients with malignant hematologic malignancies. The next goal will be to increase the response rate of CAR-T therapy and reduce its side effects. At the 60th Annual Meeting of ASH in 2018, researchers suggested to introduce targeted drugs, immunological checkpoint inhibitors, and stem cell transplantation therapy into the application of CAR-T therapy as clinical trials have shown that combination therapy can enhance the response rate of CAR-T therapy and reduce its side effects.

1. When using CAR-T therapy for CLL, taking Ibrutinib may improve its efficacy and reduce side effects.

When CAR-T therapy is used to treat refractory chronic lymphocytic leukemia (CLL), administration of the targeted BTK inhibitor Ibrutinib before, during, and after treatment can reduce adverse effects and improved response rates of CAR-T treatment compared with single-agent CAR-T therapy.

2. Blocking the immune system response may enhance the benefits and persistence of CAR-T therapy.

CAR-T therapy can effectively treat relapsed B-cell acute lymphoblastic leukemia (B-ALL). Most patients return to CAR-T cells with long-lasting efficacy, but for some patients, CAR-T cells have limited time of cancer resistance effect, which may be due to the inhibition of CAR-T cells by the autoimmune checkpoint system.

Author's Bio: 

As a leading chemical supplier, BOC Sciences keeps close watch on the recent research interests in the pharmaceutical industry and is increasingly involved with cancer therapy. To accelerate the drug discovery and design process, BOC Sciences offers a comprehensive collection of immune checkpoint inhibitors for selection and a wide range of services, such as Carbohydrate synthesis, Bioconjugation, X-ray crystallography, Biosynthesis, Superparamagnetic Iron Oxide Nano/Micro Particles Preparation, Formulation Service, Virtual Screening, antibody drug conjugates, etc.