Five real-life cases of adult patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) were recently detailed in an article in Blood — along with the rationales for selecting CD19-directed CAR-T therapy or the CD3/CD19 bispecific antibody, blinatumomab, as the first CD19-targeted treatment approach for each patient case.
While both blinatumomab and CD19-directed CAR-T therapy (ie, tisagenlecleucel in patients 25 years or younger) are approved by the US Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell ALL, the mechanisms of action of these therapies are very different: the former drug activates T cells by linking them through their CD3 receptor to the CD19 surface antigen on B cells, whereas CD19-directed CAR-T therapy uses autologous T cells that have been genetically modified to express the CD19 receptor.
Nevertheless, both treatment approaches are considered tolerable and potentially curative in the setting of relapsed/refractory B-cell ALL. Furthermore, it may be possible to subsequently offer the alternative CD19-targeted treatment if disease progression occurs following treatment with either CD19-directed CAR-T therapy or blinatumomab. However, some patients will become ineligible for subsequent treatment with the alternative approach due to loss of B-cell expression of CD19.
“Once the decision to use CD19-targeted immunotherapy to treat a patient with advanced ALL has been made, the physician faces the challenge of selecting between blinatumomab and CAR T cells,” the study authors noted, adding that “it is crucial to weigh all considerations for each individual patient before selecting one immunotherapy over another.”
In the patient cases highlighted in this article, multiple factors were considered in making individualized treatment decisions.
For example, initial treatment with blinatumomab was selected for an older patient with low-burden disease, given its FDA approval across all age groups, its lower associated risks of severe cytokine release syndrome and neurotoxicity compared with CAR-T therapy, and its demonstrated efficacy in patients with low-burden disease. Furthermore, because allogeneic hematopoietic stem cell therapy (allo-HCT) was planned for this patient who had a matched sibling donor, another factor weighing in favor of blinatumomab was the avoidance of delays associated with CAR-T manufacturing.
Factors associated with selection of CD19-directed CAR-T therapy as the initial CD19-directed approach included the presence of extramedullary disease in the central nervous system (CNS), as there is evidence supporting CNS penetration by CAR-T cells, as well as promising antileukemic activity in patients with extramedullary disease.
In addition, CAR-T therapy was preferred for a patient who experienced disease progression following allo-HCT and was unlikely to receive a second allo-HCT, given evidence for long-lasting remissions even without consolidation allo-HCT following treatment with CAR-T therapy.
In this context, the study authors stated that “blinatumomab in this setting is better used as a bridging therapy rather than a definitive curative treatment.”
The study authors concluded that “treatment with blinatumomab and CD19 CAR T cells holds promise in advanced ALL, allowing more patients to attain remission and possible cure with and without additional therapies. Both treatments have unique limitations and advantages, and the treating physician should be discerning when selecting treatment of each case.”
Aldoss I, Forman SJ. How I treat adults with advanced acute lymphoblastic leukemia eligible for CD19-targeted immunotherapy.[published online March 12, 2020]. Blood. 2020;135:804-813. doi: 10.1182/blood.2019002132