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ASH 2018: Concurrent Ibrutinib May Improve Outcomes, Reduce Toxicity of CAR T-Cell Therapy in Relapsed or Refractory CLL

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Key Points

  • 83% of patients in the ibrutinib cohort had either a complete or partial response to treatment, compared with 59% percent of those not receiving ibrutinib.
  • Patients receiving ibrutinib were more likely to achieve a deep molecular response.
  • 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.

For patients with difficult-to-treat chronic lymphocytic leukemia (CLL), continuing to take ibrutinib (Imbruvica) before, during, and after receiving chimeric antigen receptor (CAR) T-cell therapy may be associated with less severe adverse effects and better responses compared with outcomes for a similar group of patients who received the same CAR T-cell therapy without ibrutinib. These findings were presented by Gauthier et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 299).

“These results suggest that combining ibrutinib with CAR T-cell therapy may lead to better outcomes by improving efficacy and reducing toxicity,” said lead study author Jordan Gauthier, MD, of the Fred Hutchinson Cancer Research Center, in a statement.

The study was small, involving a total of 43 patients, and was not a randomized controlled trial, so the findings should be confirmed in a larger, prospective trial, he said.

Previous Trial

Prior to this study, Dr. Gauthier’s colleagues had conducted an early-phase study of CAR T cells as a 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’ 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 cytokine release syndrome (CRS).

Study Methods

In this study, researchers enrolled a second group of 19 patients 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 3 months after receiving the same CAR T-cell therapy. Dr. Gauthier and his colleagues then compared this group’s outcomes with the earlier group of patients who had discontinued ibrutinib before receiving CAR-T.

Eighty-three percent of patients in the ibrutinib cohort had either a complete or partial response to treatment, compared with 59% percent 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.

The researchers observed that 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).

“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 Gauthier. “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.”

Because those who received ibrutinib and CAR T-cell therapy 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.

The next step will be to prospectively study the effects of ibrutinib combined with CAR T-cell immunotherapy in a larger cohort.

This study was supported by Juno Therapeutics, Inc, a Celgene Company.

Disclosure: See the study authors’ full disclosures at ash.confex.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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