Celyad has reported clinical results showing the first time a patient has fully recovered from acute myeloid leukemia thanks to a CAR-T therapy, and without the need for chemotherapy preconditioning. 

At the AACR meeting in Chicago this week, Celyad has presented preliminary data from three of its ongoing Phase 1 clinical trials with a new version of the popular CAR-T technology. The company makes T cells express a natural killer receptor that targets eight different tumor ligands simultaneously.

So far, Celyad’s CAR-T therapy, called CYAD-01, has shown a “favorable safety profile,“ without the life-threatening side effects, such as cytokine release syndrome and neurotoxicity, typical of most other CAR-T cells. Including Kymriah and Yescarta, the only two CAR-T therapies already on the market.

But, most importantly, Celyad has been the first to report that a patient with acute myeloid leukemia (AML) has been free of cancer so far for 9 months after being treated with its CAR-T therapy, followed by a bone marrow transplant.

“This is the first time CAR-T has ever worked in AML,“ CEO Christian Homsy told me. “It is also the first time CAR-T has been found to be effective, in one patient, without the addition of [chemotherapy] preconditioning.“

As Homsy points out, this has been observed in only one of three patients with AML in the trial — the other two responded initially but relapsed after 2 and 4 months. But it still opens the possibility of using CAR-T cells without the need of intensive chemo beforehand. Celyad will be testing the efficacy and safety of its CAR-T therapy with and without preconditioning to determine which one has the best risk-benefit profile.

“We are now running many different Phase 1 trials to look at what are the best conditions to have a higher chance of success,“ says Homsy. “By the end of 2019 we aim to be in a position to start a pivotal trial with AML, like the ZUMA-1 trial was for Kite.“

Celyad is not the only CAR-T developer going after AML — a much bigger indication that those of Kymriah and Yescarta. Cellectis is testing an off-the-shelf version of CAR-T in AML, though its trial was halted temporarily after a patient’s death. Juno Therapeutics has also started a clinical trial in AML.

Besides the AML trials, Homsy expects to have proof of concept data for CYAD-01 in solid tumors — which are especially challenging to target for CAR-T cells — as well as with an off-the-shelf CAR-T that does not require individualized manufacturing. His ultimate goal is to further improve the impact that CAR-T has had in cancer.

“If you think about CD19 CAR-T today, in the context of B-ALL, Kite has one of the best response rates ever, of around 35% objective response at 6 months,“ he told me. “That means that 65% of patients still do not respond; Can we do better than that?“

Images via Shutterstock

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  • Salith Sasidharakurup

    Well this is interesting that the two who had a relapse, did they had a transplant as well or they didn’t ?
    But even if they had a transplant are claiming they didn’t need immunosuppressants or just they didn’t need to give immunosuppressants for the conditioning but had to give for the transplant.
    I believe the ultimate goal is to have this medication without a transplant and definitely without immunosuppressants!

    • Labiotech.eu

      Hi Salith, let me try to answer your question to the best of my knowledge, considering we don’t work with Celyad and we have not been involved in this clinical study.
      From what I know these patients could not get a transplant until they were in complete remission, which was not the case for the two patients that relapsed.
      For the patient that did show complete remission, a transplant followed (I’m guessing including immunosuppressants as per the usual protocol) because this is an experimental therapy and it would not have been ethical to not give this person the chance to recover from their cancer when they were in the right condition to get a curative transplant. Hopefully, as this treatment is tested in more patients we will know whether it’s possible to treat cancer without the need of immunosuppressants.

      • Salith Sasidharakurup

        Hi Clara,
        Thank you. That was informative. Hope they publish the work very soon.