Title: Autologous anti-CD19-transduced CD3+ cells for previously treated B-precursor acute lymphoblastic leukaemia in adults [ID1494]
Funder: Department of Health and Social Care

Abstract: Acute lymphoblastic leukaemia (ALL) is a cancer of lymphocyte-producing cells. Lymphocytes are white blood cells that are vital for the body's immune system. In ALL there is an excess production of immature lymphocyte-precursor cells, called lymphoblasts or blast cells, in the bone marrow. This affects the production of normal blood cells and there is a reduction in the number of red cells, white cells and platelets in the blood. ALL can be classified into 3 groups based on immunophenotyping: B-precursor ALL (also known as precursor-B-cell ALL); mature B-cell ALL and T-cell ALL. In adults, around 75-80% of ALL cases are classified as B-precursor ALL. [1] B-precursor ALL is characterised by the presence of cytoplasmic immunoglobulins and CD10, CD19, CD22 and CD79a expression. A specific chromosomal abnormality known as the ‘Philadelphia chromosome’ is present in 20 to 30% of adults with ALL.[2]_x000D_ _x000D_ ALL is most common in children, adolescents and young adults, with around 65% of cases diagnosed in people aged under 25. [3] A second increase in incidence is observed in people aged over 60 (around 13% of cases). [3] It is also more common in men (around 6 out of 10 cases) than women. [3] In the UK, around 350 cases of ALL are diagnosed in adults each year. [4]_x000D_ _x000D_ The aim of treatment in ALL is to achieve a cure. Treatment for newly diagnosed ALL can take up to 3 years to complete and is generally divided into 3 phases: induction, consolidation and maintenance. _x000D_ _x000D_ During induction, newly diagnosed ALL is generally treated with chemotherapy combinations including prednisolone, vincristine, an anthracycline and asparaginase. Consolidation treatment typically includes intensified chemotherapy, followed by lowdose chemotherapy in the maintenance phase. A tyrosine kinase inhibitor (such as imatinib or dasatinib) would also be offered to people with Philadelphia-chromosomepositive ALL at all phases of treatment (i.e., in addition to induction, consolidation and maintenance therapy)._x000D_ _x000D_ Around 45% of ALL relapses after or becomes refractory to initial treatment and requires further treatment. [5] There is no universally accepted treatment approach for relapsed or refractory ALL. [6] Treatment may include conventional combination chemotherapy and for most people this would be fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) with idarubicin. Adults with Philadelphia-chromosome-positive relapsed or refractory disease can have a tyrosine kinase inhibitor alone or in combination with conventional chemotherapy. _x000D_ _x000D_ In adults with relapsed or refractory disease, the following NICE technology appraisal (TA) guidance is relevant:_x000D_ • TA450 recommends blinatumomab as an option for Philadelphiachromosome-negative relapsed or refractory precursor B-cell ALL in adults _x000D_ • TA451 recommends ponatinib as an option for Philadelphia-chromosomepositive ALL in adults with the T315I gene mutation or for whom dasatinib or imatinib cannot be used _x000D_ • TA541 recommends inotuzumab ozogamicin as an option for treating relapsed or refractory CD22-positive B-cell precursor ALL in adults _x000D_ • TA554 recommends tisagenlecleucel therapy for use within the Cancer Drugs Fund as an option for treating relapsed or refractory B cell ALL in people aged up to 25. _x000D_ Other treatment options may include stem cell transplantation if a suitable donor can be found, or best supportive care (including palliative care)._x000D_ _x000D_ References_x000D_ 1. Leukaemia Foundation. Acute lymphoblastic leukaemia. Accessed June 2021._x000D_ 2. Cancer Research UK. Research into acute lymphoblastic leukaemia. Accessed June 2021._x000D_ 3. Cancer Research UK. Acute lymphoblastic leukaemia (ALL) statistics. Accessed June 2021._x000D_ 4. Leukaemia Care. Acute Lymphoblastic Leukaemia (ALL). Accessed June 2021._x000D_ 5. Fielding AK, Richards SM, Chopra R et al. (2007) Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 109(3):944-50._x000D_ 6. BMJ Best Practice. Acute lymphocytic leukaemia. Accessed June 2021.

Lay abstract: To appraise the clinical and cost effectiveness of autologous anti-CD19-transduced CD3+ cells within its marketing authorisation for treating relapsed or refractory Bprecursor acute lymphoblastic leukaemia in adults.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS