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Relapsed/Refractory CLL: Evaluating Other Novel Agents

Insights From: Michael Choi, MD, UC San Diego Medical Center; Matthew S. Davids, MD, Dana-Farber Cancer Institute; William Wierda, MD, PhD, MD Anderson Cancer Center
Published: Wednesday, May 30, 2018



Transcript: 

Michael Choi, MD: It is certainly an exciting, gratifying time to be treating patients with CLL, with new therapies and new combinations that are highly active. At the University of California, San Diego, we are excited to be developing a therapy of our own, as well—a drug called cirmtuzumab. This is a monoclonal antibody that inhibits something called ROR1, which is an orphan receptor kinase that is expressed in CLL cells but not expressed in normal B cells or normal adult tissues. We have completed a phase I trial and are now initiating a phase II trial to combine this with ibrutinib for treating patients with CLL or patients with mantle cell lymphoma.

Cirmtuzumab is something we’re very excited about at our institution. We’re eager to see how it works and helps patients with these diseases, and we certainly look forward to working with other institutions to further this.

Ublituximab is a new engineered anti-CD20 monoclonal antibody. It was tested in combination with ibrutinib for patients with relapsed and refractory disease. Dr. Jeffrey P. Sharman presented and published these results last year. That study showed that the combination of those 2 drugs led to a response rate higher than what was reported with single-agent ibrutinib, albeit at a fairly early time point, I believe—at the 6-month point. Some may question whether this simply means that the combination led to responses sooner, that many patients with ibrutinib who aren’t in a PR by 6 months are headed toward a PR once they clear that treatment-related lymphocytosis. However, I think the combination of ublituximab and ibrutinib did show more rapid remissions and higher response rates.

Selinexor is an inhibitor of XPO1, or exportin-1, a molecule that is involved in transporting proteins from nucleus to cytoplasm. When overexpressed in CLL or in lymphomas or in malignancy, it is thought to export some tumor suppressor genes such as TP53 and therefore lead to their inactivation. Some groups, including the group at Ohio State University, have also shown, interestingly, that overexpression of exportin-1 leads to other ways to activate the B-cell receptor signaling pathway. Based on this, selinexor is in a few clinical trials, including trials for patients who have progressed on ibrutinib and trials for patients who have had Richter’s transformation. I understand that some of the early data from that trial did show activity in that group of patients who have a large unmet need.

Transcript Edited for Clarity 
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Transcript: 

Michael Choi, MD: It is certainly an exciting, gratifying time to be treating patients with CLL, with new therapies and new combinations that are highly active. At the University of California, San Diego, we are excited to be developing a therapy of our own, as well—a drug called cirmtuzumab. This is a monoclonal antibody that inhibits something called ROR1, which is an orphan receptor kinase that is expressed in CLL cells but not expressed in normal B cells or normal adult tissues. We have completed a phase I trial and are now initiating a phase II trial to combine this with ibrutinib for treating patients with CLL or patients with mantle cell lymphoma.

Cirmtuzumab is something we’re very excited about at our institution. We’re eager to see how it works and helps patients with these diseases, and we certainly look forward to working with other institutions to further this.

Ublituximab is a new engineered anti-CD20 monoclonal antibody. It was tested in combination with ibrutinib for patients with relapsed and refractory disease. Dr. Jeffrey P. Sharman presented and published these results last year. That study showed that the combination of those 2 drugs led to a response rate higher than what was reported with single-agent ibrutinib, albeit at a fairly early time point, I believe—at the 6-month point. Some may question whether this simply means that the combination led to responses sooner, that many patients with ibrutinib who aren’t in a PR by 6 months are headed toward a PR once they clear that treatment-related lymphocytosis. However, I think the combination of ublituximab and ibrutinib did show more rapid remissions and higher response rates.

Selinexor is an inhibitor of XPO1, or exportin-1, a molecule that is involved in transporting proteins from nucleus to cytoplasm. When overexpressed in CLL or in lymphomas or in malignancy, it is thought to export some tumor suppressor genes such as TP53 and therefore lead to their inactivation. Some groups, including the group at Ohio State University, have also shown, interestingly, that overexpression of exportin-1 leads to other ways to activate the B-cell receptor signaling pathway. Based on this, selinexor is in a few clinical trials, including trials for patients who have progressed on ibrutinib and trials for patients who have had Richter’s transformation. I understand that some of the early data from that trial did show activity in that group of patients who have a large unmet need.

Transcript Edited for Clarity 
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