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Axi-Cel: Large B-Cell Lymphoma ZUMA-7 Armin Ghobadi – ASH 2022

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Axi-cel: Zuma 7 was a randomized phase 3 study

By Armin Ghobadi, MD

Zuma 7 was a randomized phase three study that used Axi-Cel versus a standard of. Care chemotherapy followed by autologous transplant.

In a second line setting for most patients with relapsed refractory large B-cell lymphoma. That means adult patient with relapse refractory large B-cell lymphoma being refractory to the first line therapy or relapse within the first 12 months of therapy, they’re randomized to access lc, the 19 car versus the standard of care that was chemo followed by.

Axi-Cel outcome was superior to a standard of care, and that’s why Axi-Cel is approved as a second line for mainly large B-cell lymphoma.

Autologous stem cell transplantation, that was a standard of care at that time. And based on that study, Axi-Cel clinical outcomes were superior to a standard of care, and that’s why Axi-Cel is approved as a second line therapy for those group of patients, mainly large B-cell lymphoma. With re relapse refractory, their primary refractory relapsing within 12 months of therapy.

In this specific study, we looked at some follow up questions and that the specific phase three study. So as a clinician, when I see a patient know is approved in a second line setting, I’ll give the patient access and in a second line, because when it’s refractory relapsing quickly, then the question is what happens if the CAR T doesn’t?

Or a patient has a relapsed disease after getting a second line CAR T cell therapy. To answer that question, we looked at third line treatment in patients in Zuma 7 study in both arm patients who got access to a second line or a chemo and autologous transplant. We looked at the outcome of a. Third line therapy for those patients.

That was the main things I wanted to look at in this study and specifically we to summarize the result we showed that. Although Zuma 7 was not designed to answer subsequent therapy was the, to compare the second line treatment when patient needs cell therapy. In those patients, we had refractory disease given.

Car T earlier is seems that is better than giving it later because the outcome of a patient

Car T earlier is seems that is better than giving it later because the outcome of a patient that they got access in the second line compared with those that they got access in the standard of care. And a third line appears to be better. One. Two, if the patients treated get CAR T cell therapy and they don’t respond to car or relapse after car still they can get cellular therapy with or without transplantation as a potential effective treatment or patients that they get access.

Or CAR T in a second line setting and they don’t respond to relapse. If they get chemotherapy, they can get chemotherapy, and if they are responsive to chemo, we can consolidate their response with the transplant and that’s considered the effective treatment for those group of patients. To summarize, that was the main three things that we found in this primary analysis.

There are two that are approved in this setting is liso-cell and Axi-Cel

A standard of care right now is when a patient has a primary refractory diffuse large B-cell lymphoma over last than 12 months. They get CAR C 19 car and there are two that are approved in this setting is liso-cell and Axi-Cel if they fail, that means they don’t respond to second line car. Or they relapse after that.

There is no standard of care really for them. Those patients treated are doing really poorly. They are in general, they are considered to go on a clinical trial and get additional treatments. And specifically in this study we showed that. Because they failed cell therapy once, it doesn’t mean that you can’t try cell therapy again for this patient.

Actually, that’s a viable treatment. Even if they failed, they didn’t respond to relapse. You can give them cell therapy again, and even you can give them cell therapy and transplant the patient, or you can give them chemotherapy and transplant the patients. So there is no standard. Basically, we are trying to shine.

Basically the light and the outcome of that close to 300 patients that enroll in that phase three trial. What happened to them when they went to that third line setting?

This Zuma 7 was designed to answer a specific question at the time of the study started a standard of care patient with diffuse large B-cell lymphoma when they are ref, refractory to chemotherapy, first line treatment, or relapsing within 12 months. The standard treatment was to give them chemotherapy and if they are responding to chemo, get autogalous transplant.

Randomized one-on-one Axi-Cel versus a standard of care, chemo and transplant.

So that was a standard of care based on the efficacy of car we without, and designer of the C that basically actually, instead of giving chemo, and then if you’re responding, get an autologous transplant, you can give CAR T cell therapy to those adult patients and that’s gonna be better. So to answer this question, you had to come up with a randomized and compare a standard of care that was chemo and transplant versus basically getting the car. And that’s why that’s the way that was designed, randomized one-on-one Axi-Cel versus a standard of care, chemo and transplant.

Regarding patients that they get earlier, second line car versus getting it later after failing a standard of care car, a standard of care chemotherapy median outcome. For example, an Axi-Cel arm that they got, Axi-Cel as a second line treatment median progression-free survival was around 1516. versus when you were getting a third line setting after failing chemotherapy was around six months.

Axi-Cel or CAR T cell therapy: In this study, their complete response rate was 65% versus 35%.

response rate, if you were getting access in a second line setting response rate, complete remission rate was 65% to access. But if you wait, give chemo and chemo doesn’t work, give. Axi-Cel or CAR T. In that scenario, we see interline setting. In this study, their complete response rate was 35%, 65% versus 35%.

So that’s why, although Zuma 7 was not designed to answer basically second versus third line. But when you look at those number, it appears that when you need CAR T cells desperate to give it earlier, the if patients that they fail second line CAR T cell therapy means they don’t respond or relapse later. When you look at those patients, if they get chemotherapy, the standard thing is going back and majority of the patient getting some sort of chemotherapy.

And when they get chemotherapy, Respond, you do autologous transplant for them as a treatment That is well known. We have done it for a long time. That is effective for those patients that they are consider chemosensitive. So if you do chemo and patient respond and give them auto gas transplant. So if compare those versus.

The rest that they don’t respond or they don’t get autologous transplant, the outcome appears significantly better With transplant specifically, for example median progression-free survival with additional transplant was around 12 to 13 months versus without transplant. Grew was two months, so that was obvious.

If you basically respond to chemo or chemo, you are chemo sensitive. Getting consolidation with auto transplant is gonna improve your outcome.

Zuma 7 had the primary endpoint of event-free survival and the outcome for AXI-Cel.

So Zuma 7 had the primary endpoint of event-free survival and the outcome. Original phase three study has been published in medicine and presented in at ASH last year as well. And obviously met the endpoint was Axi-Cel arm was significantly better than a standard care chemo, followed blood auto gastro transplant.

Here we actually report the result of the randomized phase three trial, the follow up of what happened next for those patients.

The common questions that I have to is if my patients and my colleagues have, if I use CAR T cell therapy in a second line setting and patients don’t respond to relapse, what to do and we really don’t know what’s gonna be the best strategy. The result that we are presenting here is gonna. Should some light on some data at least that we have right now to guide decision making for those patients.

Specifically as I said, if you can get cell therapy again and do transplant, the survival option, if you can get the chemo to a patient, a different type of chemo and take them to auto gastro transplant, that’s a viable option. So all result basically help us in decision making for those patients here really.

Second line CAR T cell therapy for a patient that your primary refractory or relapsed within 12 months is a standard of care. We have to, we need to refer those patient as soon as possible so we can take them to the most effective treatment that they need in a second line setting one. And if they don’t respond to.

Car t cells or their progressive disease relapsed later, will still have effective options for those patients.

 

About the Author: Armin Ghobadi, MD

Bone Marrow Transplant Specialist, Medical Oncologist

Primary Academic Title

Associate Professor of Medicine, Division of Medical Oncology, Washington University School of Medicine

Clinical Expertise

 

As a member of our leukemia and lymphoma specialist teams, Dr. Ghobadi cares for patients diagnosed with leukemia and lymphoma through treatment and recovery. Learn more about Dr. Ghobadi and the Blood and Marrow Transplant Program at Siteman.

 

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Disclaimer: This listing may not include all articles associated with this physician and may include publications related to other physicians with a similar name.

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