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Factors Associated with Outcomes After a Second CD19-Targeted CAR-T Cell Infusion for Refractory B-Cell Malignancies, Including Chronic Lymphocytic Leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

CAR-T is often wrongly viewed as the last stop on the CLL therapy train, but that is hardly true. Not only are there many therapies to consider or reconsider post-CAR-T, one can even repeat the CAR-T infusion (CAR-T2).

This study of second CAR-T infusions was small, and the results weren’t spectacular. Only three of nine chronic lymphocytic leukemia (CLL) patients responded, with two of those reaching complete remission (CR). All three responding CLL patients had undetectable measurable disease (uMRD) at day 28 post-CAR-T2. The median Progression-Free Survival (PFS) was 61 days and Overall Survival (OS) was seven months.

Those numbers are not stellar, but these were difficult to treat patients who had an average of six prior lines of therapy, and six of the nine had bulky disease.

The study demonstrated that the “conditioning” regime used for both CAR-T1 and CART-T2 was critical to the outcome. Conditioning refers to the chemotherapy given before infusion of the CAR-T cells for lymphodepletion (decreasing the number of lymphocytes) to prevent rejection of the CAR-T cells. Cy-Flu (cyclophosphamide and fludarabine) worked best.

They also found that a higher dose of CAR-T cells led to longer persistence of the re-engineered cells and better outcomes.

These last two points are important as they suggest best practices moving forward. For example, all three responding CLL patients received Cy-Flu lymphodepletion before both CART1 and CART2. Research such as this is helping clinicians to fine-tune the protocols to improve the chance of success by finding out the best conditioning protocols and the best dose of CAR-T cells.

Here is a link to the abstract in the journal, Blood: Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies.

For more background on CAR-T see CAR-T and Other Cellular Therapies.

Stay strong. We are all in this together.

Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.