The Department of Medicine of LKS Faculty of Medicine, The University of Hong Kong (HKUMed) has successfully performed Chimeric Antigen Receptor T-cell (CAR-T cell) treatment for a patient with B-cell acute lymphoblastic leukaemia, who relapsed after bone marrow transplantation and was refractory to salvage chemotherapy. This is the first time that CAR-T cell therapy has been used outside clinical trials to treat blood cancer patients in Hong Kong. The treatment was carried out by the Division of Haematology, Medical Oncology and Haemopoietic Stem Cell Transplantation, Department of Medicine, HKUMed and Queen Mary Hospital. In fact, the team performed the first ever CAR-T cell therapy in Hong Kong (for a lymphoma patient) in May 2020. From then, Queen Mary Hospital is not only the first, but also the only centre in Hong Kong to perform CAR-T cell treatment for patients with blood cancers. The team believes this therapy has set the new direction for cancer treatment in future, which is expected to benefit more patients in similar conditions.
Living Medicine: CAR-T are genetically modified T cells to target and destroy cancers
In general, the curative effect of conventional therapy for recurrent acute lymphocytic leukemia or lymphoma is far from satisfactory. Repeated chemotherapy induces limited response. A few patients may be cured by haematopoietic stem cell transplantation, but there are transplant related toxicities. Some patients may still relapse after the transplant.
In recent years, the medical profession has been researching on immunotherapies with longer-lasting curative effects, including CAR-T cell therapy, which kill cancer cells through the patient’s own immune system. Under CAR-T cell therapy, normal T cells are harvested from the patient. A ‘chimeric antigen receptor’, which allows T cells to identify a specific type of cancer cells, is added to these T cells ex vivo. Genetically modified CAR-T cells are then re-infused to the patient, so that they can locate the cancer cells and eliminate them. This is the latest technology of cell therapy.
CAR-T cell therapy effectively improves the chance of cure. According to the statistics of the Hong Kong Cancer Information and Statistics Center of the Hospital Authority, more than 100 patients are suitable for this treatment each year.
Hong Kong’s first patient successfully treated outside clinical trials
Former Hong Kong beach volleyball team member Mr Lau, 25, is the first leukaemia patient in Hong Kong who has successfully received Tisagenlecleucel treatment. Diagnosed with B-cell acute lymphoblastic leukemia in 2018, Mr Lau achieved disease remission after chemotherapy and received haematopoietic stem cell transplantation in February 2019. However, he relapsed twice afterwards. Thus the medical team recommended CAR-T cell therapy as further chemotherapy was deemed not effective on the patient.
Mr Lau received CAR-T cell treatment in October 2020 and gradually recovered without serious complications. Recent bone marrow examinations could find no leukaemia cells, indicating that a cure might have been achieved.
CAR-T cell therapy: a new direction for cancer treatment in the future
Tisagenlecleucel is the first and currently the only CAR-T cell therapy approved in Hong Kong, which was registered with Hong Kong’s Department of Health under the Pharmacy and Poisons Ordinance on 5 March 2020. Specifically, the treatment is applicable to the following:
1) Paediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplantation or in second or later relapse.
2) Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
CAR-T cell therapy may have serious complications, such as cytokine release syndrome and immune effector cell-related neurotoxicity syndrome. The situation is very similar to the immune complications seen in allogeneic haematopoietic stem cell transplantation. Therefore, medical institutions providing CAR-T cell therapy must have solid experience in haematopoietic stem cell transplantation.
Tisagenlecleucel also involves complicated procedures, including:
1) Collect the patient’s lymphocytes
2) Store cells frozen in liquid nitrogen
3) Ship cells to overseas for genetic modification
4) Transport back to Hong Kong for re-infusion
The treatment is limited to designated medical institutions. In order to ensure the safety of the transportation process, each cell product is carefully marked with an “identity chain” to facilitate tracking of the patient. Queen Mary Hospital is the first and the only centre in Hong Kong to perform CAR-T cell treatment for patients with blood cancers.
CAR-T cell therapy for lymphoma
Tisagenlecleucel is also indicated for the treatment of relapsed/refractory B-cell lymphoma. The Division of Haematology, Medical Oncology and Haemopoietic Stem Cell Transplantation, Department of Medicine, HKUMed and Queen Mary Hospital is currently conducting a clinical trial of tisagenlecleucel in B-cell lymphoma, and seven patients so far have been recruited into this phase 3 study.
In order to benefit more patients, the international medical community has developed a variety of CAR-T cell therapies to deal with more cancers. For example, the US Food and Drug Administration (FDA) has approved two other CAR-T cell therapies – Axicabtagene Ciloleucel for relapsed or refractory large B-cell lymphoma, and Brexucabtagene Autoleucel to treat relapsed or refractory “mantle cell lymphoma”.