CAR-T therapy has changed the game in cancer treatment. But what happens when the game changes again and a patient relapses? Whether it's after early line or later line CAR-T, a relapse can leave patients and clinicians wondering what now? Are bispecific antibodies the next step? Can you get CAR-T again, or should you be considering other treatment options?
In this HealthTree University lesson, we're breaking down the evolving landscape of post-CAR-T treatment options from retreatment strategies to where bispecifics fit in, and what current data and clinical practice are telling us.
What treatments could patients consider if they relapsed after a CAR-T that was given after four prior lines of therapy?
In 2025, most of our patients relapsing after CAR-T receive that CAR-T after many lines of therapy, which will be different than patients who relapse after an early CAR-T. So I think that's one difference we need to recognize.
So patients who've kind of seen everything then came to CAR-T still will usually have had, you know, one, two, three, maybe five years of treatment free time. And so they're generally then have all of the therapies available to them again. So we recycle therapies that maybe have worked well. So anything that gave that patient a remission for 18 months or longer, and in general, in our small studies that we've done, with our patients, we've shown that another T-cell redirection tends to be better than any of the old traditional chemotherapies.
So while, say, a bispecific may not work as well after CAR-T than in a patient who's never had anything targeting BCMA in a patient who's had a BCMA, CAR-T, nothing will work as well as a bispecific.
So a few caveats. You know, we do have now bispecifics with two different targets. So being able to target GPRC in place of BCMA may be helpful. But years after the CAR-T usually that relapse, the patient will have BCMA expressed and so would be able to get a bispecific targeting BCMA.
Let's say somebody has had a CAR-T, right. So what can we do next? Can they receive bispecifics?
So absolutely, if somebody has failed a CAR-T in later line, and you know, they've seen a lot of the drugs combination, they might have had a transplant. They've seen a lot of the drugs that we commonly are able to use and have used. Generally, the new immunotherapies, are available, like I mentioned bispecific certain they are an option, including the BCMA bispecifics, but also the GPRC5D bispecifics.
And we have a lot of clinical trials and development. We have different targeted CAR-Ts. We have combination of bispecifics with other drugs, whether it be with daratumumab, pomalidomide. We have trispecifics coming down the pipeline, and we have CELMoDs and combinations. So there's and we have dual targeted CAR-T's multiple ongoing clinical trials with those.
I mean the future is not looks so bright. There are multiple, clinical trials and newer targets being developed, and in clinical trial and hopefully will come into practice soon.
What happens if a patient has relapsed on both CAR-T and bispecifics?
CAR-T, you know, is a cellular therapy. It does its job. And they kind of leave and you're done bispecifics requires the T-cells be continuously engaged. So many times if you're relapsing after a bispecific it's due to T-cell exhaustion like these cells. You just don't have T cells, you know, ready to keep doing the work. You just don't have T cells, you know, ready to keep doing the work.
So there are two slightly different scenarios, but we certainly can then go back to the earlier therapies, which they may have received in different combinations. So putting them together in different ways.
Another thing we've done quite a few times for patients who are still eligible and maybe still have stem cells, is to do a stem cell transplant. Not so much for the myeloma therapy, but really as a way to reboot the bone marrow so that you then have healthy T cells or a healthier immune system and the rest of the microenvironment, so that they then will respond better to pretty much any of our therapies.
What is a stem cell boost?
Sometimes we can use a stem cell transplant or what we call a stem cell boost. That is not quite so much chemotherapy but bringing in stem cells to reboot the immune system. So we now have all of the parts of the immune system functioning. And maybe the T cells that were exhausted due to prior BCMA, bispecifics, can now be present and be activated. And now we can, repurpose the the previously given bispecifics.
PACE-based therapy is a strong combination of chemotherapy drugs used for myeloma that isn't responding to other treatments. The PACE drugs are cisplatin, doxorubicin, cyclophosphamide, and etoposide. Sometimes other medications are added to this base to make the treatment even stronger or better suited to a patient's disease. It's typically used to control aggressive myeloma or as a bridge to other therapies, and is given under close medical supervision.
Is there any role for PACE-based therapies?
That's to me an emergency brake. So whenever the myeloma is growing a little too fast and we may be, in danger of harming kidneys or bones or in general are in a rush to turn it around. I think the DCEP and pace combination still have a role. It's just we don't ever expect those to last very long. So it really is a step to get them to something else. It's not a therapy in and of itself.
Relapsing after CAR-T therapy doesn't mean the end of the road. It means it's time for a new strategy. Whether it's bispecific antibodies, clinical trials, a second CAR-T, or a whole new approach, the landscape of options is growing and so is the hope.
As we learn more about how to sequence and personalize these therapies, one thing becomes clear. The future of myeloma care is adaptable, evolving, and increasingly patient focused.
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Thanks for watching. And remember, knowledge is power, especially in the fight against cancer.