Cancer: Earlier targeted CAR T therapy could improve outcomes for high-risk large B cell lymphoma
March 22, 2022
Earlier treatment with axicabtagene ciloleucel — a type of immunotherapy known as ‘CAR T’ that specifically targets the CD19 surface protein of cancerous B cells — elicited a complete response in 78% of 37 patients with high-risk large B cell lymphoma (LBCL), according to a phase 2 clinical trial published in Nature Medicine. These findings suggest that this type of CAR T cell therapy — which also demonstrates a manageable safety profile — may be clinically beneficial in an earlier treatment setting than is typically used.
Patients with high-risk LBCL — a type of blood cancer characterized by specific gene mutations and/or a combination of clinical attributes — generally respond poorly to standard, initial rounds of chemoimmunotherapy. Axicabtagene ciloleucel (axi-cel) is a type of CAR T cell therapy — an immunotherapy in which a patient’s own immune cells, in this case T cells, are modified in the laboratory so that they can better recognize and fight cancer cells. Axi-cel targets the surface protein CD19 expressed on immune cells known as B cells that are cancerous and is already approved for use in patients with B cell lymphomas in later stages of treatment. However, its potential as an initial treatment for those with high-risk LBCL has yet to be investigated.
Sattva Neelapu and colleagues conducted a phase 2 clinical trial of axi-cel as an initial treatment for 40 adult patients (median age of 61 years; 68% male) with high-risk LBCL. The trial was single-arm, which means that all participants received the treatment. Of the 37 patients included in the efficacy analysis, 78% achieved a complete response — the primary outcome of the trial. At the time of data cut-off — with a median follow-up of 15.9 months — medians for duration of response, progression-free survival and event-free survival had not been reached. Adverse safety events were consistent with those previously reported for axi-cel.
These results support further testing of CD19-targeting CAR T cells in earlier stages of disease treatment. However, follow-up in large randomized trials with a direct comparison to standard chemoimmunotherapy is needed.
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