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ASCO 2019: Dr. Koffman’s Pick #5 MRD Negative Responses after Liso-Cel or JCAR017 in 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In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, counts down his top ten CLL related abstract from ASCO or the American Society of Clinical Oncology Annual Meeting held May 31 – June 4, 2019, Chicago, IL.

#5

TRANSCEND CLL 004: Minimal residual disease (MRD) negative responses after lisocabtagene maraleucel (Liso-Cel; JCAR017), a CD19-directed CAR T cell product, in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL / SLL).

This is a multi-centered trial led Dr. Tanya Siddiqi using the CAR-T drug JCAR017 or Liso-Cel that is essentially the same construct as JCAR014 that I received in Seattle on March 22, 2018. By. All measurements, I am cancer free as I write this.

For those new to CAR-T, you might enjoy our CAR-T comic book for a simple introduction.

CAR-T uses the patient’s own T cells that have been genetically modified to attack CLL, specifically in this case CD19, a surface marker found on all normal and cancerous B cells.

Takeaways:

  • 16 CLL / SLL patients were presented in these data at ASCO 2019.
  • All had received ≥2 prior lines of prior therapy.
  • 3/4 had high-risk features (TP53 mutation, complex karyotype, or del17p).
  • All had received prior ibrutinib and half had prior venetoclax. This was a tough group of patients to treat who were running out of options.
  • There were serious side effects and risks:
    • One patient needed to have the dose of Liso-cel adjusted due to high blood pressure.
    • Most of the patients had significantly low blood counts.
    • One had serious cytokine release syndrome (CRS), a systemic inflammatory reaction where cytokines (inflammatory enzymes) are excessively released.
    • Three had serious neurological toxicity.
  • There were very encouraging results:
    • 13 of 15 responded to the CAR-T therapy.
    • 7 pts (47%) achieved complete remission.
    • 2/3 or 10 of 15 pts achieved undetectable MRD (U-MRD) in blood by day 30 and in 7/8 pts (88%) in the bone marrow.

Conclusions:

While the adverse events were significant, there were no deaths in this difficult to treat CLL population and there was an 87% response rate with the majority of patients having no detectable disease by the end of one month.

While not for everyone, CAR-T therapy is clearly a potent choice for those CLL patients running out of choices.

Here is my brief video review of this ASCO abstract:

Here is a link to the ASCO abstract itself: TRANSCEND CLL 004: Minimal residual disease (MRD) negative responses after lisocabtagene maraleucel (Liso-Cel; JCAR017), a CD19-directed CAR T cell product, in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymph.

Thanks for staying informed.

Stay strong. We are in this together.

Brian