In 2018, the FDA approved the listing of 59 new drugs, setting a historical record. From small molecules to antibody-conjugated drugs, from bispecific T cell adapters to CAR-T cell therapies, cancer will continue to be one of the hottest areas of medical research and development in 2019. This article will combine eValuatePharma's recently released EP Vantage 2019 Preview, which evaluates the market potential of new drugs in the world, has been invented into two new CAR-T anticancer therapies in late clinical development in 2019. 

One of CAR-T anticancer therapies: JCAR017

Company: New Base (Celgene)

New Base's JCAR017 is a CAR-T therapy targeting CD19 developed by its subsidiary Juno Therapeutics. According to the latest data released at the American Society of Hematology Annual Meeting (ASH2018) in 2018, JCAR017 achieved up to 81% in a phase 1/2 clinical trial of patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Objective response rate and 43% complete response rate. In 2019, Phase 2/3 clinical data on this CAR-T therapy for lymphoma and leukemia will be announced, and it will be the third FDA-approved CAR-T therapy.

CAR-T anticancer therapy II: bb2121

Company: New Base / bluebird bio

In the field of treating hematological cancer, B cell mature antigen (BCMA) is a potent target. Bb2121 is a CAR-T cell therapy that targets BCMA targets and has been approved by the FDA for breakthrough therapy. The current phase 2 clinical trial of bb2121 for the treatment of patients with relapsed/refractory multiple myeloma has been completed. Bb2121 has the potential to be a "first-in-class" targeted BCMA therapy for multiple myeloma. I look forward to the FDA making a decision on this therapy by 2020!

The comments in the EP Vantage 2019 Preview report show that the blood cancer data is amazing, and we have seen a lot of encouraging information. Despite the 2018, sales of Gilead Yescarta and Novartis's Kymriah were lower than expected. But in 2019, cell therapy may be an exciting year. In addition, several BCMA updates to the CAR-T program have shown that multiple myeloma-associated antigens are considered to be the next important antigen following CD19.

What is CAR-T therapy?

Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) refers to a T cell in which a chimeric antigen receptor (CAR) is introduced into a T cell to produce tumor-specific recognition. CAR-T is similar to other immunotherapies. Its basic principle is to use the patient's own immune cells to clear cancer cells.

CAR-T production preparation flow chart

Process of treatment of CAR-T therapy

Patient Assessment : Patients need to perform many tests and screenings to determine if CAR-T therapy is appropriate for them.

T cell collection : T cells are collected from patients by separation. In the process, blood is separated from the T cells by a machine, and the remaining blood is returned to the patient.

Transforming T cells : T cells are sent to the laboratory for genetic modification to produce chimeric antigen receptors (CARs) on their surface. CAR allows T cells to recognize antigens on the surface of tumor cells.

T cell expansion : In the laboratory, genetically engineered T cells continue to grow until thousands, which typically takes several weeks. When the CAR T cells are large enough, they are frozen and sent to the hospital where the patient is located.

T cell reinfusion : Shortly after chemotherapy, the patient was admitted to the hospital and the doctor reinfused the CAR T cells into the body like a blood transfusion. This is a one-time process, although patients may need to stay in the hospital for a few weeks to monitor their overall condition and response to treatment and side effects. (Before receiving CAR T cell infusion, patients may receive chemotherapy for their cancer first. This helps create more space for injected CAR T cells, allowing them to expand and proliferate in humans.)

Recovery phase : The recovery period for CAR T therapy lasts approximately 2-3 months. After receiving a CAR T cell infusion, the patient is staying in the hospital for 1 to 3 weeks, during which time the doctor monitors their response to the treatment and manages the side effects. After the patient is discharged from the hospital, they will need regular follow-up in the next few months to assess side effects and response to treatment. During this period, the patient may have side effects and be hospitalized again, but this is rare. 

Note : The type and severity of side effects that occur in a patient varies from person to person and there is a risk of serious complications within a few weeks of treatment. Generally, these complications are temporary and will resolve or get treated on their own. Possible side effects include cytokine release syndrome, an inflammation that has symptoms like flu (high fever/chilling), but may also include hypotension and dyspnea, as well as other organ dysfunction, as well as the nervous system. Problems, such as confusion, difficulty understanding language speech, or coma. Because each patient's condition is different, the patient needs to communicate with the doctor in advance.

What are the CAR-T cell therapies that the FDA has approved?

1 Novartis: Kymriah (tisagenlecleucel)

On August 31, 2017, the US FDA approved Kymriah (tisagenlecleucel), the first gene therapy for CAR-T cell therapy, for acute lymphoblastic leukemia (ALL) in children and young adult patients. Such therapeutic drugs are approved to give cancer and other serious and life-threatening diseases new legal treatment options.

2 Kate Pharmaceuticals: Yescarta (axicabtagene ciloleuce)

On October 18, 2017, (FDA) approved the CAR-T cell therapy drug Yescarta (axicabtagene ciloleucel, abbreviated as KTE-C19) for relapsed or refractory large B-cell lymphatics previously treated with second- or multi-line system Treatment of adult patients with LBCL, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBL), and follicular Lymphoma (FL) DLBCL (ie, transformed FL, TFL). This drug is not suitable for the treatment of patients with primary central nervous system lymphoma.

The principle of Yescarta and Kymriah is to genetically modify the patient's T cells to express a chimeric antigen receptor (CAR) targeting the antigen CD19, an antigenic protein expressed on the surface of various blood tumor cells. Includes B cell lymphoma and leukemia cells.

Introduction to the Dana Faber Cancer Institute Blood Oncology Center 

The Dana-Farber Cancer Institute was founded in 1947. It is a cancer specialist hospital of Harvard Medical School, a comprehensive cancer treatment center and AIDS research center designated by the US federal government. One of the founding members of the Bo/Harvard Cancer Center has produced a Nobel Prize in Medicine.

The Leukemia Center is known worldwide for its professional diagnosis and treatment of leukemias and related diseases at all stages and types. The center's transplant program is known for its blood and bone marrow transplants and is a blood and bone marrow transplant center authorized by the Cell Therapy Foundation, which conducts transplants for more than 120 patients each year.

Central treatment of various stages and types of leukemia and related diseases, including: acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, hairy cell leukemia, lymphoblastic lymphoma, myelodysplasia , bone marrow fiber degeneration, etc.

 Richard M. Stone, MD

Department: Internal Medicine

Title: Professor of Internal Medicine, Harvard Medical School

Inauguration Hospital: Dana Farber Cancer Institute

Areas of expertise: leukemia, myelodysplastic syndrome, diagnosis and treatment of bone marrow-enhancing diseases

Richard M. Stone graduated from Harvard Medical School in 1981 with a Doctor of Clinical Medicine (MD). He was trained as a medical resident in Brigham and Women's Hospital, and then completed a fellowship in hematology and oncology at the Dana Farber Cancer Hospital. He has worked on a wide range of clinical and basic medicine research on acute leukemia and related diseases and has been invited to do medical reports around the world.

Dr. Richard M. Stone is currently the Director of the Adult Acute Leukemia Research Program at the Dana Farber Cancer Hospital and a member of the Clinical Oncology Committee of the American College of Internal Medicine and a member of the Hematology Committee. He is also the vice chairman of the National White Blood Cell Clinical Trials Cooperative Research Council. His clinical treatment and research interests focus on bone marrow stem cell diseases, including acute leukemia, myeloproliferative disorders and myeloproliferative disorders.