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Predicting Which CLL Patients May Respond to CAR-T Therapy

In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

Authored by Dr. Brian Koffman

Bottom Line:

Liso-cel, a CAR-T therapy, is effective but only in a minority of CLL patients. A lower disease burden improved response rates, and poor markers were not a factor.

Who Performed the Research and Where Was it Presented:

Dr. Bill Wierda from MD Anderson Cancer Center gave a prestigious oral presentation on behalf of his colleagues at the 2024 European Hematology Association (EHA) Annual Meeting in Madrid.

Background:

Lisocabtagene Maraleucel (liso‐cel) is the only approved CAR-T therapy for CLL patients. Its labeled indication in relapsed / refractory (R/R) chronic lymphocytic leukemia (CLL) is restricted to those who have failed at least two prior lines of treatment, including a BTKi and BCL2i. In this tough-to-treat group, the overall response rate has been less than half, and less than one in five have a complete response (CR) that is often associated with a lengthy remission. As the therapy can be difficult (though the mortality rate is very low) and expensive, it would be good to be able to predict who is most and least likely to benefit from the treatment.

Methods and Participants:

Eighty-seven patients with R/R CLL / SLL from TRANSCEND CLL 004 were studied. Post hoc analyses were performed to search for correlations linking the likelihood of achieving a complete response (CR), partial response (PR), or combined as an overall response with specific patient features such as demographics, disease state, and biomarkers.

Results:

  • Of the 87 patients, 16 had a CR, 25 had a PR, 40 had stable or progressive disease, and 6 could not be evaluated.
  • Lower beta-2 microglobulin (B2M) at screening was observed in patients achieving CR.
  • Earlier-stage disease (Rai stage 0–II) at the time of initial screening was predictive of achieving CR.
  • Those with smaller lymph nodes showed trends towards achieving CR.
  • Pretreatment characteristics correlated with a higher chance of responding with any response (CR or PR) included:
    • absence of bulky disease and smaller lymph nodes.
  • There was no correlation between reaching a CR and/or PR and
    • age,
    • sex,
    • mutated TP53,
    • deletion of 17p,
    • unmutated immunoglobulin heavy-chain variable region (IGHV),
    • complex karyotype.

Discussion:

To live up to its promise, CAR-T therapy outcomes must improve beyond one in five with durable responses. Fortunately, there are several promising paths forward. Combining liso-cel with other medications to augment and/or complement its activity and the next generation of “armed” or dual target CAR-Ts are exciting developments. Choosing which patients might have the best chance to be successful is another method to improve outcomes, and that is what these post hoc analyses offer us.

Summary:

The great news is that liso-cel, like the other cellular therapy used in CLL / SLL, namely allogeneic hematopoietic stem cell transplant (HSCT) or “bone marrow” transplant, seems to be agnostic to all the traditional poor prognostic markers. This has not been the case with older chemo-immunotherapies and, to some extent, newer targeted therapies. The CAR-T cells are good killers of even the toughest CLL cells.

However, it does seem that a greater disease burden, specifically an advanced RAI stage, bigger nodes, and higher B2M (which reflects more disease activity), is associated with a poorer outcome. The story is similar to a transplant. There are only so many cells to do all the cancer killing, and they can get tired.

CAR-T therapy is an important element in treating CLL. Studies such as this help us better understand its best role going forward.

Links:

Listen to my monologue below.

Predicting Which CLL Patients May Respond to CAR T Therapy

Read the abstract at: CHARACTERISTICS ASSOCIATED WITH RESPONSE TO LISOCABTAGENE MARALEUCEL (LISO‐CEL) IN PATIENTS (PTS) WITH R/R CLL / SLL: EXPLORATORY ANALYSES FROM TRANSCEND CLL 004

Stay strong; we are all in this together.

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