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Brentuximab Vedotin Overview and Treatment Advice

Insights From: Neha Mehta-Shah, MD, Washington University School of Medicine in St. Louis
Published: Monday, Jan 28, 2019



Transcript: 

Neha Mehta-Shah, MD: So in the relapsed/refractory setting, the prognosis is generally relatively poor in peripheral T-cell lymphomas. The median survival is often quoted at about 6 months. That means that there are some patients who do have durable remissions to their therapy, and we all certainly have patients who have lived many years from their time of relapse. But the majority, half the patients, will die within 6 months of relapse. So there have been a number of efforts to improve this.

There are 4 drugs approved for relapsed/refractory peripheral T-cell lymphoma. Two of those are histone deacetylase inhibitors like romidepsin or belinostat. One of them is pralatrexate, which is a folate analogue or a methotrexate analogue. And then brentuximab vedotin is approved for patients who have relapsed peripheral T-cell lymphoma that expresses CD30. The overall response rate to brentuximab in the anaplastic large cell lymphoma population—remember those are diseases that always express CD30—is 85%. And some of those patients, we believe, may have very long-term remissions to brentuximab alone. And so that’s an important drug in the treatment of peripheral T-cell lymphomas.

Most of our patients with peripheral T-cell lymphomas are older. The median age is often 65 or 70 for this disease population. Anaplastic large cell lymphoma, especially ALK-positive anaplastic large cell lymphoma, happens in younger patients, often patients in their 20s and 30s. And so decreasing cumulative toxicity is important, actually, for both subgroups. Our older patients often have a hard time tolerating therapy that can be difficult on the body for reasons of nausea, or vomiting, or decreased blood counts. And our younger patients can suffer from long-term toxicity such as neuropathy from medicine like brentuximab, which is known to cause neuropathy. So understanding the adverse effect profile and helping modulate both the dose and intensity is important when treating these patients.

I think for romidepsin, which is usually given weekly, 3 weeks on and 1 week off, for patients who are responding and have been responding for a number of months and doing well on treatment, we sometimes think about spacing out their treatment and doing it every other week to help mitigate some of the adverse effects, which are usually fatigue or nausea, vomiting, and electrolyte abnormalities. Brentuximab is known to cause cumulative neuropathy in the T-cell lymphoma population just like the Hodgkin lymphoma population. And so most patients will develop neuropathy after 16 cycles or so.

There are occasionally patients who can tolerate significantly more than that. But the neuropathy, if it develops, can be long-standing. And so with evidence of neuropathy, my personal practice is to dose-reduce patients. And for patients who we know might be on brentuximab longer term, who may not be candidates for other curative treatment like allogeneic stem cell transplants, I consider spacing out the brentuximab intervals also, to make them not every 3 weeks but maybe every 4 weeks, so that the dosage intensity is not as harsh. And we think that that might mitigate against some of the neuropathy, although that’s all anecdotal.

Transcript Edited for Clarity
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Transcript: 

Neha Mehta-Shah, MD: So in the relapsed/refractory setting, the prognosis is generally relatively poor in peripheral T-cell lymphomas. The median survival is often quoted at about 6 months. That means that there are some patients who do have durable remissions to their therapy, and we all certainly have patients who have lived many years from their time of relapse. But the majority, half the patients, will die within 6 months of relapse. So there have been a number of efforts to improve this.

There are 4 drugs approved for relapsed/refractory peripheral T-cell lymphoma. Two of those are histone deacetylase inhibitors like romidepsin or belinostat. One of them is pralatrexate, which is a folate analogue or a methotrexate analogue. And then brentuximab vedotin is approved for patients who have relapsed peripheral T-cell lymphoma that expresses CD30. The overall response rate to brentuximab in the anaplastic large cell lymphoma population—remember those are diseases that always express CD30—is 85%. And some of those patients, we believe, may have very long-term remissions to brentuximab alone. And so that’s an important drug in the treatment of peripheral T-cell lymphomas.

Most of our patients with peripheral T-cell lymphomas are older. The median age is often 65 or 70 for this disease population. Anaplastic large cell lymphoma, especially ALK-positive anaplastic large cell lymphoma, happens in younger patients, often patients in their 20s and 30s. And so decreasing cumulative toxicity is important, actually, for both subgroups. Our older patients often have a hard time tolerating therapy that can be difficult on the body for reasons of nausea, or vomiting, or decreased blood counts. And our younger patients can suffer from long-term toxicity such as neuropathy from medicine like brentuximab, which is known to cause neuropathy. So understanding the adverse effect profile and helping modulate both the dose and intensity is important when treating these patients.

I think for romidepsin, which is usually given weekly, 3 weeks on and 1 week off, for patients who are responding and have been responding for a number of months and doing well on treatment, we sometimes think about spacing out their treatment and doing it every other week to help mitigate some of the adverse effects, which are usually fatigue or nausea, vomiting, and electrolyte abnormalities. Brentuximab is known to cause cumulative neuropathy in the T-cell lymphoma population just like the Hodgkin lymphoma population. And so most patients will develop neuropathy after 16 cycles or so.

There are occasionally patients who can tolerate significantly more than that. But the neuropathy, if it develops, can be long-standing. And so with evidence of neuropathy, my personal practice is to dose-reduce patients. And for patients who we know might be on brentuximab longer term, who may not be candidates for other curative treatment like allogeneic stem cell transplants, I consider spacing out the brentuximab intervals also, to make them not every 3 weeks but maybe every 4 weeks, so that the dosage intensity is not as harsh. And we think that that might mitigate against some of the neuropathy, although that’s all anecdotal.

Transcript Edited for Clarity
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