New Agents, Durable Responses in CLL
Hello. I am John Gribben, Professor and Chair of Medical Oncology at Barts Cancer Institute, Barts and the London School of Medicine in London, United Kingdom. Welcome to this edition of Medscape Oncology Insights on chronic lymphocytic leukemia (CLL). Today I would like to discuss several of the important CLL studies that were presented at the 2012 annual congress of the European Hematology Association (EHA) here in Amsterdam.
The clinical session today was dominated by very exciting presentations of clinical studies using new classes of agents in CLL. Dr. Susan O'Brien presented follow-up data on monotherapy with ibrutinib. This is a small molecule inhibitor of a protein called Bruton tyrosine kinase (BTK), which is involved in signaling through the B-cell receptor. This agent induces impressive responses, and the novel data presented today were that these responses appeared durable with only 1 patient progressing on therapy and all other patients continuing on therapy for more than 1 year and having continuing responses, including complete remissions.
All patients, including those with deletion 17p, who usually fail to respond well to chemotherapy, were able to remain on therapy without progression. A feature of this class of drug is that patients first experience a rise in white blood cell count as the cells leave the lymph nodes. As the lymph nodes shrink, the lymphocyte count goes up. When this was first seen with this class of drugs, people were concerned that this was representing progressive disease. We are now aware that as these cells leave the lymph nodes the cells die off within the circulation, and as the patients remain on these therapies over time the response rates continue to rise.
Dr. Jennifer Brown presented data today that this agent can be combined with bendamustine or rituximab.This combination was associated with an increase in the response rate, and the use of these 2 agents blunted the rise in lymphocyte count, so that we could see these responses without that early rise in lymphocyte count in the blood that occurs with monotherapy with this agent.
Another exciting new agent is dinaciclib, which is a cyclin-dependent kinase (CDK) inhibitor. The studies presented from Ohio State led by Dr. John Byrd demonstrated that this drug is effective, and they have established the dose from phase 1 studies that are now going to enable this drug to move forward into definitive studies with this exciting class of agent. We have seen very impressive responses, including tumor lysis syndrome, with this class of agent suggesting that, in common with other CDK inhibitors, we have to consider the use of the agent very carefully in patients who have very high white counts or bulky lymphadenopathy.
The last class of drugs was described in 2 presentations on BCL2 inhibitors. BCL2 is the protein that keeps cells alive and is overexpressed in CLL and many other cancers. Navitoclax (ABT-263) could be combined safely with fludarabine/cyclophosphamide/rituximab or bendamustine and rituximab, and data were shown for that combination today. However, Abbott's (Abbott Laboratories; Worcester, Massachusetts) new agent (ABT-199) was shown to induce very impressive responses without inducing the low platelet count that had been a feature of ABT-263 treatment. This agent is now entering the next phase of clinical trial development in combination with anti-CD20 monoclonal antibodies.
The reason for the excitement in the field is that after years of using the same kind of agents we now have a large number of new agents that show great activity in CLL. The challenge that we as a community now face is how we are going to design and carry out the trials required to get these exciting agents available for our patients so that they are not only available within clinical trials but can really move the field forward. With that, I would like to thank you for joining me for this edition of Medscape Oncology Insights. This is John Gribben reporting from EHA 2012 in Amsterdam.
Hello. I am John Gribben, Professor and Chair of Medical Oncology at Barts Cancer Institute, Barts and the London School of Medicine in London, United Kingdom. Welcome to this edition of Medscape Oncology Insights on chronic lymphocytic leukemia (CLL). Today I would like to discuss several of the important CLL studies that were presented at the 2012 annual congress of the European Hematology Association (EHA) here in Amsterdam.
Impressive Responses to Ibrutinib
The clinical session today was dominated by very exciting presentations of clinical studies using new classes of agents in CLL. Dr. Susan O'Brien presented follow-up data on monotherapy with ibrutinib. This is a small molecule inhibitor of a protein called Bruton tyrosine kinase (BTK), which is involved in signaling through the B-cell receptor. This agent induces impressive responses, and the novel data presented today were that these responses appeared durable with only 1 patient progressing on therapy and all other patients continuing on therapy for more than 1 year and having continuing responses, including complete remissions.
All patients, including those with deletion 17p, who usually fail to respond well to chemotherapy, were able to remain on therapy without progression. A feature of this class of drug is that patients first experience a rise in white blood cell count as the cells leave the lymph nodes. As the lymph nodes shrink, the lymphocyte count goes up. When this was first seen with this class of drugs, people were concerned that this was representing progressive disease. We are now aware that as these cells leave the lymph nodes the cells die off within the circulation, and as the patients remain on these therapies over time the response rates continue to rise.
Dr. Jennifer Brown presented data today that this agent can be combined with bendamustine or rituximab.This combination was associated with an increase in the response rate, and the use of these 2 agents blunted the rise in lymphocyte count, so that we could see these responses without that early rise in lymphocyte count in the blood that occurs with monotherapy with this agent.
Promising Data on Dinaciclib, Navitoclax
Another exciting new agent is dinaciclib, which is a cyclin-dependent kinase (CDK) inhibitor. The studies presented from Ohio State led by Dr. John Byrd demonstrated that this drug is effective, and they have established the dose from phase 1 studies that are now going to enable this drug to move forward into definitive studies with this exciting class of agent. We have seen very impressive responses, including tumor lysis syndrome, with this class of agent suggesting that, in common with other CDK inhibitors, we have to consider the use of the agent very carefully in patients who have very high white counts or bulky lymphadenopathy.
The last class of drugs was described in 2 presentations on BCL2 inhibitors. BCL2 is the protein that keeps cells alive and is overexpressed in CLL and many other cancers. Navitoclax (ABT-263) could be combined safely with fludarabine/cyclophosphamide/rituximab or bendamustine and rituximab, and data were shown for that combination today. However, Abbott's (Abbott Laboratories; Worcester, Massachusetts) new agent (ABT-199) was shown to induce very impressive responses without inducing the low platelet count that had been a feature of ABT-263 treatment. This agent is now entering the next phase of clinical trial development in combination with anti-CD20 monoclonal antibodies.
The reason for the excitement in the field is that after years of using the same kind of agents we now have a large number of new agents that show great activity in CLL. The challenge that we as a community now face is how we are going to design and carry out the trials required to get these exciting agents available for our patients so that they are not only available within clinical trials but can really move the field forward. With that, I would like to thank you for joining me for this edition of Medscape Oncology Insights. This is John Gribben reporting from EHA 2012 in Amsterdam.
SHARE
![Pediatric Supportive Care (PDQ®): Supportive care - Patient Information [NCI]-Overview](https://cdnus.oss-us-west-1.aliyuncs.com/libs/images/NewsJpg/cate_6/072_215x160.jpg)
