Obecabtagene autoleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia [ID6347]

Acute lymphoblastic leukaemia (ALL) is a cancer of lymphocyte-producing cells. Lymphocytes are white blood cells that are vital for the bodys 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 split into B-cell and T-cell types based on immunophenotyping.

B-cell ALL can be divided into further subgroups based on the maturity of the cells (precursor B-cell ALL mature B cell ALL common ALL and pro B cell ALL); precursor B-cell ALL accounts for around 75% of all cases of ALL.

A specific chromosomal abnormality known as the ‘Philadelphia chromosome’ is present in 20 to 30% of adults with ALL.(1)ALL is most common in children adolescents and young adults with around 65% of cases diagnosed in people aged under 25. A second increase in incidence is observed in people aged over 60 (around 13% of cases).

ALL is more common inmen than women.(2) In England around 650 new cases of ALL were diagnosed in 2021. (3) The 5-year survival rate following diagnosis of ALL is approximately 90% for children under 15 65% for people aged between 15 and 39 and 20% for adults aged 40 and over.(1)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.

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 low dose chemotherapy in the maintenance phase. For high risk ALL stem cell transplantation may also be used as consolidation therapy.

A tyrosine kinase inhibitor (such as imatinib or dasatinib) would also be offered to people with Philadelphia-chromosome positive ALL at all phases of treatment.(1)Around 45% of ALL in adults relapses after or becomes refractory to initial treatment and requires further treatment.(4) There is no universally accepted treatment approach for relapsed or refractory ALL.

Treatment may include conventional combination chemotherapy and for most people this would be fludarabine cytarabine and granulocyte colony-stimulating factor (FLAG) with idarubicin.(5) Adults with Philadelphia-chromosome-positive relapsed or refractory disease can have a tyrosine kinase inhibitor alone or in combination with conventional chemotherapy.NICE technology appraisal guidance 975 recommends tisagenlecleucel therapy as an option for people 25-years and under for treating B-cell acute lymphoblastic leukaemia that is relapsed after a transplant relapsed for a second or later time or refractory.NICE technology appraisal guidance 893 recommends brexucabtagene autoleucel for use within the Cancer Drugs Fund as an option for treating relapsed or refractory B-cell ALL in people 26-years and over.NICE technology appraisal guidance 541 recommends inotuzumab ozogamicin as an option for treating relapsed or refractory CD22-positive B-cell precursor ALL in adults.NICE technology appraisal guidance 451 recommends ponatinib as an option for Philadelphia-chromosome positive ALL in adults with the T315I gene mutation or for whom dasatinib or imatinib cannot be used.NICE technology appraisal guidance 450 recommends blinatumomab as an option for Philadelphia chromosome-negative relapsed or refractory precursor B-cell ALL in adults.Other treatment options may include stem cell transplantation if a suitable donor can be found or best supportive care (including palliative care).References1.

Cancer Research UK (2021). Acute lymphoblastic leukaemia (ALL). Accessed August 2024.2. Cancer Research UK (2021). Acute lymphoblastic leukaemia (ALL) statistics. Accessed August 2024.3. NHS Digital (2023) Cancer registration statistics 2021. Accessed August 2024.4.

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):944-50.5. BMJ Best Practice (2024). Acute lymphoblastic leukaemia. Accessed August 2024.