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Axi-Cel and Future of CAR T-Cell Therapy in Lymphoma

Panelists: Krishna V. Komanduri, MD, Sylvester Comprehensive Cancer Center; David Maloney, MD, PhD, Fred Hutchinson Cancer Research Center; Sattva S. Neelapu, MD, University of Texas MD Anderson Cancer Center; Michael Pulsipher, MD, Children
Published: Tuesday, Feb 13, 2018



Transcript:

Sattva S. Neelapu, MD: On this study, we found 2 types of adverse events, which are typical for any CAR T-cell therapy. The most common side effect that we observed is cytokine release syndrome. This is a system-made inflammatory reaction. Patients may get high fevers and they may typically feel as if they are having a severe case of flu. But the majority of the adverse events with cytokine release syndrome that we noted were grade 1 and grade 2. About 13% of the patients developed grade 3 or higher cytokine release syndrome. The second most common toxicity that we observed is neurological toxicity, and patients can sometimes get confused, disoriented, but this also appeared to be transient, and the majority of them were grade 1 and grade 2. About 31% of the patients developed grade 3 or higher in neurological toxicity, but all of the neurological toxicities have resolved without any residual neurological deficits in these patients. And these toxicities typically occur within the first 1 to 2 weeks after administration of the axi-cel. We now have long-term safety data on this study and, in fact, we have not seen any late onset cytokine release syndrome or neurological events related to this product.

So, in patients with aggressive B-cell non-Hodgkin’s lymphoma, when they’re initially diagnosed they are typically treated with R-CHOP or a R-CHOP-like chemotherapy regimen, and that is estimated to cure about 60% of those patients. But if they relapse or progress after R-CHOP, they get a second-line chemotherapy followed by autologous stem cell transplantation. And that is estimated to cure an additional 5% of the patients. Now with this axi-cel being FDA approved, we have a third-line option, which we did not have available previously. With axi-cel, we estimate that an additional 15% of the patients may be potentially cured. So, altogether, in patients who are newly diagnosed with large-cell lymphoma today, we think approximately 80% of all patients are curable using these 3 modalities.

But we have, still have, a lot more work to do. In the near future, we will be initiating a clinical trial where we will directly compare axi-cel with autologous stem cell transplantation in the second-line setting to see if it is more efficacious than autologous stem cell transplantation. And we will also be thinking about evaluating axi-cel in the frontline setting in patients, especially high-risk, who have aggressive non-Hodgkin’s lymphoma such as high-grade B-cell lymphomas. In addition, we are also thinking about adding axi-cel in patients with mantle cell lymphoma as well as indolent B-cell non-Hodgkin’s lymphoma. And preliminary data such as that are likely to be effective in those B-cell lymphoma subtypes as well.

So, with the FDA approval of axi-cel in patients who failed 2 or more lines of prior therapies, I think it’s important to refer these patients as soon as they fail the second-line therapy. The longer these patients wait, the sicker they become, and they have more tumor at the time of infusion with axi-cel, they’re likely to develop more toxicities. Moreover, if the patients become very sick and they develop other comorbidities, they’re likely to be eligible for this therapy. So, it’s best to refer those patients as early as possible to the treating institution—currently, at least, there are 16 centers in the United States—that have been activated to administer axi-cel therapy under the standard of care setting. In the near future, over the next year, up to 80 to 90 centers may be available across the United States to be able to administer this axi-cel therapy.

So, I think this is particularly an exciting time to be in the field of lymphoma research or hematological cancer research with these exciting developments with CAR T-cell therapy. I think this gives a lot more hope to the patients who die from this disease. Currently, in the United States, approximately 20,000 patients with non-Hodgkin’s lymphoma die each year. The approval of this product, the first ever product approved by the FDA for aggressive B-cell non-Hodgkin’s lymphoma, is a remarkable indication and remarkable progress for patients with non-Hodgkin’s lymphoma. And it provides hope for those patients who previously had no cure, no treatment options. So, we think that it is likely to cure a significant proportion of those patients, and then certainly in other patients, it’s also likely to prolong their life significantly.

Transcript Edited for Clarity

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Transcript:

Sattva S. Neelapu, MD: On this study, we found 2 types of adverse events, which are typical for any CAR T-cell therapy. The most common side effect that we observed is cytokine release syndrome. This is a system-made inflammatory reaction. Patients may get high fevers and they may typically feel as if they are having a severe case of flu. But the majority of the adverse events with cytokine release syndrome that we noted were grade 1 and grade 2. About 13% of the patients developed grade 3 or higher cytokine release syndrome. The second most common toxicity that we observed is neurological toxicity, and patients can sometimes get confused, disoriented, but this also appeared to be transient, and the majority of them were grade 1 and grade 2. About 31% of the patients developed grade 3 or higher in neurological toxicity, but all of the neurological toxicities have resolved without any residual neurological deficits in these patients. And these toxicities typically occur within the first 1 to 2 weeks after administration of the axi-cel. We now have long-term safety data on this study and, in fact, we have not seen any late onset cytokine release syndrome or neurological events related to this product.

So, in patients with aggressive B-cell non-Hodgkin’s lymphoma, when they’re initially diagnosed they are typically treated with R-CHOP or a R-CHOP-like chemotherapy regimen, and that is estimated to cure about 60% of those patients. But if they relapse or progress after R-CHOP, they get a second-line chemotherapy followed by autologous stem cell transplantation. And that is estimated to cure an additional 5% of the patients. Now with this axi-cel being FDA approved, we have a third-line option, which we did not have available previously. With axi-cel, we estimate that an additional 15% of the patients may be potentially cured. So, altogether, in patients who are newly diagnosed with large-cell lymphoma today, we think approximately 80% of all patients are curable using these 3 modalities.

But we have, still have, a lot more work to do. In the near future, we will be initiating a clinical trial where we will directly compare axi-cel with autologous stem cell transplantation in the second-line setting to see if it is more efficacious than autologous stem cell transplantation. And we will also be thinking about evaluating axi-cel in the frontline setting in patients, especially high-risk, who have aggressive non-Hodgkin’s lymphoma such as high-grade B-cell lymphomas. In addition, we are also thinking about adding axi-cel in patients with mantle cell lymphoma as well as indolent B-cell non-Hodgkin’s lymphoma. And preliminary data such as that are likely to be effective in those B-cell lymphoma subtypes as well.

So, with the FDA approval of axi-cel in patients who failed 2 or more lines of prior therapies, I think it’s important to refer these patients as soon as they fail the second-line therapy. The longer these patients wait, the sicker they become, and they have more tumor at the time of infusion with axi-cel, they’re likely to develop more toxicities. Moreover, if the patients become very sick and they develop other comorbidities, they’re likely to be eligible for this therapy. So, it’s best to refer those patients as early as possible to the treating institution—currently, at least, there are 16 centers in the United States—that have been activated to administer axi-cel therapy under the standard of care setting. In the near future, over the next year, up to 80 to 90 centers may be available across the United States to be able to administer this axi-cel therapy.

So, I think this is particularly an exciting time to be in the field of lymphoma research or hematological cancer research with these exciting developments with CAR T-cell therapy. I think this gives a lot more hope to the patients who die from this disease. Currently, in the United States, approximately 20,000 patients with non-Hodgkin’s lymphoma die each year. The approval of this product, the first ever product approved by the FDA for aggressive B-cell non-Hodgkin’s lymphoma, is a remarkable indication and remarkable progress for patients with non-Hodgkin’s lymphoma. And it provides hope for those patients who previously had no cure, no treatment options. So, we think that it is likely to cure a significant proportion of those patients, and then certainly in other patients, it’s also likely to prolong their life significantly.

Transcript Edited for Clarity
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