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Follicular Lymphoma: Obinutuzumab and Chemotherapy

Insights From: Stephen M. Ansell, MD, PhD, Mayo Clinic; Radhakrishnan Ramchandren, MD, Wayne State University School of Medicine
Published: Friday, Jan 26, 2018



Stephen M. Ansell, MD, PhD: Obinutuzumab is a new anti-CD20 antibody that builds on the successes of rituximab, a standard anti-CD20 antibody, which is currently in widespread use. The goal was to make it more effective in inducing antibody drug-dependent cytotoxicity, and that has been successfully achieved. It is now being tested clinically to see whether it is better than standard rituximab therapy.

In this trial, the study specifically looked at the use of chemotherapy in combination with obinutuzumab versus chemotherapy in combination with rituximab, with ongoing maintenance therapy thereafter—with either obinutuzumab or rituximab. This study also met its primary endpoint, showing an improved progression-free survival for patients receiving the obinutuzumab treatment. Patients could receive that treatment in combination with either CHOP chemotherapy, bendamustine chemotherapy, or even with CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy. Across the board, the combination with chemotherapy was improved. So, that’s again an indication that has been approved by the FDA—for the use of obinutuzumab.

Radhakrishnan Ramchandren, MD: The value of this is still debatable amongst clinicians, largely because we need to better understand what the role of PFS is when there’s no overall survival benefit. There’s been a multitude of studies of improved PFS but not overall survival—for example, rituximab maintenance in this setting. This is an indolent disease in which treatments can be repeated and patients may undergo a variety of anti-CD20 agents as they proceed through the course of their disease over time.

While this study did demonstrate a progression-free survival benefit, the overall benefit of this needs to be understood with time. Personally, I do not generally use obinutuzumab for every patient with follicular lymphoma. There are circumstances in which I think a progression-free survival benefit may be very important. For instance, an older patient in whom you feel that it’s unlikely that you’re going to get multiple lines of therapy, sequentially, may benefit from an initial progression-free survival benefit.

It is important to note that in this study, all patients received maintenance with either rituximab or obinutuzumab. That, too, is somewhat debatable. So, in patients where there is not a plan to receive maintenance therapy or in whom the doctor would not give maintenance therapy, this study may not prove to be equally beneficial in the obinutuzumab and rituximab arms.

Transcript Edited for Clarity
 
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Stephen M. Ansell, MD, PhD: Obinutuzumab is a new anti-CD20 antibody that builds on the successes of rituximab, a standard anti-CD20 antibody, which is currently in widespread use. The goal was to make it more effective in inducing antibody drug-dependent cytotoxicity, and that has been successfully achieved. It is now being tested clinically to see whether it is better than standard rituximab therapy.

In this trial, the study specifically looked at the use of chemotherapy in combination with obinutuzumab versus chemotherapy in combination with rituximab, with ongoing maintenance therapy thereafter—with either obinutuzumab or rituximab. This study also met its primary endpoint, showing an improved progression-free survival for patients receiving the obinutuzumab treatment. Patients could receive that treatment in combination with either CHOP chemotherapy, bendamustine chemotherapy, or even with CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy. Across the board, the combination with chemotherapy was improved. So, that’s again an indication that has been approved by the FDA—for the use of obinutuzumab.

Radhakrishnan Ramchandren, MD: The value of this is still debatable amongst clinicians, largely because we need to better understand what the role of PFS is when there’s no overall survival benefit. There’s been a multitude of studies of improved PFS but not overall survival—for example, rituximab maintenance in this setting. This is an indolent disease in which treatments can be repeated and patients may undergo a variety of anti-CD20 agents as they proceed through the course of their disease over time.

While this study did demonstrate a progression-free survival benefit, the overall benefit of this needs to be understood with time. Personally, I do not generally use obinutuzumab for every patient with follicular lymphoma. There are circumstances in which I think a progression-free survival benefit may be very important. For instance, an older patient in whom you feel that it’s unlikely that you’re going to get multiple lines of therapy, sequentially, may benefit from an initial progression-free survival benefit.

It is important to note that in this study, all patients received maintenance with either rituximab or obinutuzumab. That, too, is somewhat debatable. So, in patients where there is not a plan to receive maintenance therapy or in whom the doctor would not give maintenance therapy, this study may not prove to be equally beneficial in the obinutuzumab and rituximab arms.

Transcript Edited for Clarity
 
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