ASH18: Study finds benefits in patients with CLL combining Imbruvica with CAR T-cell therapy

Results presented Sunday at the American Society of Hematology (ASH) annual meeting suggest that combining AbbVie's Imbruvica (ibrutinib) with CAR T-cell therapy can improve efficacy and reduce toxicity in patients with difficult-to-treat chronic lymphocytic leukaemia (CLL). Lead author Jordan Gauthier said "to our knowledge, these are the most encouraging results that have been seen to date in humans with a combination of CAR T cells and a targeted agent."

An earlier study involving 24 patients with CLL who had previously been treated with Imbruvica was discontinued before CD19-specific CAR T-cell therapy with Celgene's JCAR014 began, in most cases because the patients' disease seemed to worsen. However, the researchers conducted another trial on the basis that other work had indicated that continuing treatment with Imbruvica before, during and after CAR T-cell immunotherapy may be beneficial.

The second trial enrolled 19 patients with difficult-to-treat CLL who were similar in age and disease characteristics to the earlier group. The patients remained on Imbruvica before, during and for at least three months after receiving JCAR014, with results from these subjects compared to the earlier group who had discontinued AbbVie's drug before receiving CAR-T therapy.

Results showed that 83 percent of patients in the Imbruvica cohort had either a complete or partial response to treatment compared with 65 percent of those not receiving Imbruvica. Further data indicated that patients receiving Imbruvica were more likely to achieve a deep molecular response.

Meanwhile, results showed that cytokine release syndrome (CRS) occurred less frequently among those receiving Imbruvica, with no patients in this group developing severe symptoms of CRS, compared with 25 percent of those not receiving Imbruvica. Gauthier commented "while the CAR T cells expanded robustly in both groups and led to high rates of response, we did not observe a single case of severe CRS in patients receiving [Imbruvica] during CAR-T therapy."

Gauthier cautioned that because patients who received Imbruvica and CAR-T concurrently were treated more recently than those who did not, this cohort may have also benefited from improvements in the management of patients receiving CAR T-cell therapy that have occurred over time. He noted that further work will be to study the effects of AbbVie's drug combined with CAR-T therapy in a larger group of patients.

Imbruvica is currently approved in a number of different haematological malignancies, including in adults with CLL who have received at least one prior therapy. The oral BTK inhibitor is also authorised for adults with CLL with a 17p deletion and as a frontline treatment for CLL. Imbruvica, which is marketed with Johnson & Johnson, is also cleared in combination with bendamustine and Roche's Rituxan (rituximab) for adults with CLL/small lymphocytic lymphoma.

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