What types of leukemia can CAR-T treat?
The types of leukemia that can be treated clinically with CAR-T cells are acute B lymphocytic leukemia and chronic lymphocytic leukemia.
The main types of leukemia that can be treated clinically with CAR-T cells are acute B lymphocytic leukemia and chronic lymphocytic leukemia, with CD19 or CD22 as the target.
- CAR-T cells targeting CD19 can treat acute B-cell lymphocytic leukemia/B-lymphoblastic lymphoma, chronic lymphocytic leukemia, and all types of B-cell lymphoma such as diffuse large B-cell lymphoma, follicular lymphoma, set-apart lymphoma, high-grade B-cell lymphoma, and Burkitt’s lymphoma. Cases of successful treatment of multiple myeloma and CD19-expressing acute myeloid leukemia with CAR-T 19 cells have also been reported.
- CAR-T cells targeting CD22 can treat acute lymphoblastic leukemia or acute lymphoblastic leukemia that has relapsed after CAR-T 19 treatment.
Can all patients with leukemia receive CAR-T therapy?
Not all patients with leukemia can receive CAR-T cell therapy.
For T-cell acute lymphoblastic leukemia, scientists have not yet found an appropriate target for CAR-T therapy, so these patients cannot currently undergo CAR-T therapy. For acute myeloid leukemia, the current clinical efficacy of CAR-T cell therapy is generally poor or the remission time is very short, and CAR-T cell therapy is also not recommended.
Can CAR-T completely cure leukemia?
CAR-T cell therapy may cure some patients with leukemia.
Recent clinical data suggest that among patients with acute lymphoblastic leukemia, one third of those with less than 5% myeloid leukemia cells prior to CAR-T treatment but with detectable minimal residuals may achieve long-term disease-free survival; on the other hand, CAR-T cells may be 71% effective in treating chronic lymphocytic leukemia, with profound remission of sequencing IgH rearrangement negative. On the other hand, CAR-T cell therapy for chronic lymphocytic leukemia is also 71% effective, and this group of patients who achieve deep remission with sequencing IgH rearrangement negativity are likely to achieve long-term disease-free survival, which is commonly referred to as “cure.
Why does CAR-T work well for acute lymphoblastic leukemia?
Why does CAR-T work well for acute lymphoblastic leukemia?
The complete remission rate for refractory relapsed acute lymphoblastic leukemia with anti-CD19 CAR-T cells is as high as 70%-93%. The main reason for such good results is:
- First, CD19 is a near-ideal target. Because it is not only expressed frequently and at high levels in B-cell malignancies, but is also required for normal B-cell development in mice and humans, it is widely expressed in human B-lymphocytes. Thus patients successfully treated with CD19 CAR-T have severe B-cell aplasia, and administration of alternative antibody therapy (i.v. human immunoglobulin) tolerates the loss of normal B cells.
- Second, the microenvironment of solid tumors is an important driver of their biological behaviors such as proliferation, metastasis, and immune escape, with a large number of fibrous stroma and immunosuppressive cells in their microenvironment, while protecting tumor tissue against immune cell attack through physical barriers and immune credentials, unlike hematologic tumors, where there is no immune microenvironment for CAR-T cells.
Does leukemia come back after CAR-T treatment? Is there any help after relapse?
While CAR-T cells are highly effective in treating refractory relapsed acute B lymphocytic leukemia, they are prone to relapse after the disease has gone into remission. For patients who relapse, CAR-T cell therapy can be repeated with a different therapeutic target.
Can CAR-T be combined with transplantation for refractory relapsed leukemia?
CAR-T cell therapy for refractory relapsed acute B-lymphocytic leukemia is highly effective, with very high remission rates (70% to 90%) and deep remissions that can be negative for microresidual foci. To prevent relapse, patients are advised to undergo allogeneic HSCT as soon as possible after obtaining disease remission with CAR-T cell therapy, provided they have a suitable donor and are physically eligible for transplantation.