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Further Considerations for Relapsed/Refractory FL

Insights From: Carla Casulo, MD, University of Rochester Medical Center; Nathan H. Fowler, MD, University of Texas MD Anderson Cancer Center
Published: Monday, Mar 19, 2018



Transcript: 

Nathan H. Fowler, MD: We know that transplant can change the natural history of disease in patients with follicular lymphoma. The problem is that in the past—actually, still—transplants are associated with significant morbidity and mortality. We have seen from several allogeneic transplant studies that a proportion of patients, actually the majority of patients who receive allogeneic transplant with follicular lymphoma, will achieve durable remissions and potentially cure.

The problem is that allogeneic transplant in many patients with follicular lymphoma is associated with an absolute risk of mortality, and that means potentially dying during the transplant. In addition, most transplant studies select patients who are healthy enough to receive transplant, meaning a lot of patients who have relapsed follicular lymphoma will be too old or have too many comorbid conditions to proceed on with allogeneic transplant.

We have seen long-term follow-up of several autologous transplant studies recently. It does suggest that in a select group of patients who receive autologous stem cell transplant, including refractory patients, up to half of them may achieve prolonged remissions.

So, in my own practice, I think that if a patient has short remissions following chemotherapy and is healthy, I still would consider them for autologous or allogeneic transplant because I think they have the potential to change the natural history of this disease that is marked with recurrent relapses. It’s a select group of patients. The treatments are associated with significant toxicity, but in that group who achieve remission, there can be very good outcomes.

Carla Casulo, MD: The CHRONOS-1 study showed that patients who were treated with copanlisib had good response rates and a progression-free survival of about 1 year in relapsed and refractory follicular lymphoma. It’s a pan-PI3 kinase inhibitor, and it’s given as weekly IV for 3 weeks. The study looked at treating patients until either disease progression or toxicity. It has a different side effect profile compared with idelalisib, which is a delta-PI3 kinase inhibitor. Interestingly, it actually causes elevated blood sugar, hyperglycemia, and hypertension.

It’s a very distinct side effect profile compared with idelalisib, and it’s also given by vein. So, I think that it will perhaps influence the decision of the oncologist as to which, if they have to choose between 2 PI3 kinase inhibitors, are they going to select? Are they going to select idelalisib or are they going to select copanlisib? I think that’s a decision that needs to be made given the comorbidities of the patient. If a patient has poorly controlled diabetes, perhaps copanlisib may not be the appropriate agent. Or if they have poorly controlled hypertension, copanlisib may not be the appropriate agent. But I think that for third-line follicular lymphoma, we’ve demonstrated the value of 2 PI3 kinase inhibitors as well as bendamustine and obinutuzumab, which are the FDA-approved choices. But in addition to that, we have a number of different clinical trial opportunities out there for patients to try novel agents.

Transcript Edited for Clarity
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Transcript: 

Nathan H. Fowler, MD: We know that transplant can change the natural history of disease in patients with follicular lymphoma. The problem is that in the past—actually, still—transplants are associated with significant morbidity and mortality. We have seen from several allogeneic transplant studies that a proportion of patients, actually the majority of patients who receive allogeneic transplant with follicular lymphoma, will achieve durable remissions and potentially cure.

The problem is that allogeneic transplant in many patients with follicular lymphoma is associated with an absolute risk of mortality, and that means potentially dying during the transplant. In addition, most transplant studies select patients who are healthy enough to receive transplant, meaning a lot of patients who have relapsed follicular lymphoma will be too old or have too many comorbid conditions to proceed on with allogeneic transplant.

We have seen long-term follow-up of several autologous transplant studies recently. It does suggest that in a select group of patients who receive autologous stem cell transplant, including refractory patients, up to half of them may achieve prolonged remissions.

So, in my own practice, I think that if a patient has short remissions following chemotherapy and is healthy, I still would consider them for autologous or allogeneic transplant because I think they have the potential to change the natural history of this disease that is marked with recurrent relapses. It’s a select group of patients. The treatments are associated with significant toxicity, but in that group who achieve remission, there can be very good outcomes.

Carla Casulo, MD: The CHRONOS-1 study showed that patients who were treated with copanlisib had good response rates and a progression-free survival of about 1 year in relapsed and refractory follicular lymphoma. It’s a pan-PI3 kinase inhibitor, and it’s given as weekly IV for 3 weeks. The study looked at treating patients until either disease progression or toxicity. It has a different side effect profile compared with idelalisib, which is a delta-PI3 kinase inhibitor. Interestingly, it actually causes elevated blood sugar, hyperglycemia, and hypertension.

It’s a very distinct side effect profile compared with idelalisib, and it’s also given by vein. So, I think that it will perhaps influence the decision of the oncologist as to which, if they have to choose between 2 PI3 kinase inhibitors, are they going to select? Are they going to select idelalisib or are they going to select copanlisib? I think that’s a decision that needs to be made given the comorbidities of the patient. If a patient has poorly controlled diabetes, perhaps copanlisib may not be the appropriate agent. Or if they have poorly controlled hypertension, copanlisib may not be the appropriate agent. But I think that for third-line follicular lymphoma, we’ve demonstrated the value of 2 PI3 kinase inhibitors as well as bendamustine and obinutuzumab, which are the FDA-approved choices. But in addition to that, we have a number of different clinical trial opportunities out there for patients to try novel agents.

Transcript Edited for Clarity
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