Concurrent ibrutinib may improve outcomes and reduce toxicity of CAR-T-Cell therapy

<p class="article-intro">For patients with difficult-to-treat chronic lymphocytic leukemia (CLL), continuing to take ibrutinib before, during, and after receiving the CAR-T-cell therapy with JCAR014 may be associated with less severe adverse effects and better responses, compared with outcomes for a similar group of patients who received JCAR014 without ibrutinib.</p> <hr /> <p class="article-content"><p>Ibrutinib is approved by the FDA as both an initial treatment for CLL and as a treatment for difficult-to-treat CLL. Prior to this study, an early-phase study of CAR-T-cells had been conducted as single therapy in 24 patients with CLL who had previously been treated with ibrutinib. Ibrutinib had been discontinued before CAR-T-cell therapy began, in most cases because the patients&rsquo; CLL seemed to be getting worse. Other preliminary studies have suggested, however, that continuing ibrutinib treatment before, during, and after CAR-T-cell immunotherapy may prevent tumors from worsening, boost the effectiveness of the CAR-T-cells, and help to prevent CRS.<br /> In this study, a second group of 19 patients was enrolled with difficult-to-treat CLL who were similar in age and disease characteristics to the earlier group. This second group remained on ibrutinib before, during, and for at least three months after receiving the same CAR-T-cell therapy. This group&rsquo;s outcomes were compared with the earlier group of patients who had discontinued ibrutinib before receiving CAR-T.<br /> 83 % of patients in the ibrutinib cohort had either a complete or partial response to treatment compared with 65 % of those not receiving ibrutinib. Patients receiving ibrutinib were also more likely to achieve a deep molecular response, meaning that highly sensitive methods detected no malignant DNA sequences in the bone marrow.<br /> CRS occurred less frequently among those receiving ibrutinib. No patients in this cohort developed severe symptoms of CRS, compared with 25 % of those not receiving ibrutinib. Two early deaths were reported: one patient who was receiving ibrutinib (sudden death from presumed cardiac arrhythmia in the context of CRS) and one patient who was not (severe CRS and neurotoxicity).<br /> &bdquo;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,‟ said lead study author Jordan Gauthier, MD, of the Fred Hutchinson Cancer Research Center in Seattle. &bdquo;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 ibrutinib during CAR-T-therapy.‟<br /> Because those who received ibrutinib 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, Dr. Gauthier said.</p> <p><br /><strong>Reference:</strong><br />Gauthier J et al.: Comparison of efficacy and toxicity of CD19-specific chimeric antigen receptor T-cells alone or in combination with ibrutinib for relapsed and/or refractory CLL. ASH Annual Meeting 2018, abstract #299</p></p>