Dr Frederick Locke on Real-World Implications of ZUMA-7 Findings in Relapsed/Refractory LBCL

Frederick Locke, MD, vice chair, Department of Blood and Marrow Transplant and Cellular Immunotherapy Program, co-leader, Immuno-Oncology, Moffitt Cancer Center, discusses findings of the phase 3 ZUMA-7 trial presented at ASH 2021 and how use of axicabtagene ciloleucel can be optimally applied in a real-world setting.

Findings of the ZUMA-7 trial showed axicabtagene ciloleucel (axi-cel) to be an effective second-line treatment in relapsed/refractory patients with large B-cell lymphoma (LBCL), with the next steps in a real-world setting being how to streamline the payer approval process, get patients infused rapidly, and initiate therapy as soon as possible, said Frederick Locke, MD, vice chair, Department of Blood and Marrow Transplant and Cellular Immunotherapy Program, co-leader, Immuno-Oncology, Moffitt Cancer Center.

Dr Locke was the lead author of the abstract presented at ASH 2021, titled, “Primary analysis of ZUMA‑7: A phase 3 randomized trial of axicabtagene ciloleucel versus standard‑of‑care therapy in patients with relapsed/refractory large B-cell lymphoma.”


If axi-cel is to become the new standard-of-care in the second-line setting for relapsed/refractory patients with LBCL, how important is it to get patients infused quickly?

Yeah, so the ZUMA-7 trial really is groundbreaking, it shows that we can give axi-cel as the second-line treatment right away for patients who have progressed or didn't respond to front-line therapy. And what's really key is that those patients get referred in early so that we can give those patients the opportunity to get axi-cel as the second line of therapy

Your results are in a clinical trial, but in a real-world setting, how important will it be to get payers to approve primary refractory patients quickly to make certain that patients have the best chance of success–given that the universe of eligible patients will expand?

CAR T-cell therapy certainly needs authorization and insurance companies to give the OK to give it and it will be important that happens very rapidly. I think CAR T-cells have now been an approved product for a few years now, so it's not a surprise to the community and to insurers that they exist.

The results are really remarkable, you can get long-term ongoing remissions in patients with LBCL with CAR T-cell therapy. So, most of the large payers are aware of this treatment and we just have to keep working to streamline the process and get patients in rapidly and get them to therapy as soon as possible.

Is there anything more to be done to identify which patients are the best candidates for CAR T-cell therapy generally and axi-cel specifically?

CAR T-cell therapy is a treatment that is a process and it certainly is known to cause some common classifications of toxicity, the cytokine release syndrome and neurotoxicity. And so we have to think carefully about who the appropriate patients are to give CAR T-cell therapy to.

But one thing we know is that older patients, those who are 65 years of age or older, can safely get this treatment. And so we just have to get the patients referred in and let the CAR T-cell treatment center make the decision on whether the patient is fit and appropriate to get the treatment.

We feel very comfortable at our center and other centers that do CAR T-cell therapy, getting these patients through safely to the other side of the treatment. And in fact, patients recover quite quickly within a month to 2 months, 3 months, feeling back to how they did pre-treatment. So, we've got to get them in early and get them treated.

You did not have bridging chemotherapy in your study, but do you expect this to occur in a real-world setting?

In our trial we really wanted to zero in and focus on the impact of CAR T-cell therapy itself as the second-line treatment. So, we did not allow for bridging chemotherapy. In the real-world setting, patients may need some bridging chemotherapy if they have progressive disease. That being said, I mean these were quite sick patients and we feel that corticosteroids can be used in order to to temporize the disease and get the patients to that CAR T-cell treatment they need.

Importantly, axi-cel can be manufactured and sent back to the treatment center very rapidly. So, giving a cycle of chemotherapy may actually delay the treatment with CAR T-cell therapy, because you have to recover from the toxicities of chemotherapy. So, in the real world, bridging may happen, but my practice is to avoid bridging chemotherapy whenever possible.

Can you discuss future studies that will be needed to address how to treat patients after second-line?

So, the trial we conducted, ZUMA-7, was to randomize CAR T to second-line or to the current standard-of-care, which is multi-agent chemotherapy followed by autologous stem cell transplant for those that respond.

What we don't know is how to manage patients if they get CAR T-cell therapy in the second-line. What is the treatment they should get? Should they get chemotherapy and auto transplant if they respond or should they get other therapies, novel agents? I think that's an area of intense study over the next several years.

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