Novel Agents: Making the Benefit Last in CLL
Novel Agents: Making the Benefit Last in CLL
Dr. O'Brien: The strategy has to be combinations. If you are getting a partial remission with a single agent, it doesn't make much sense to stop the drug, because if you are leaving a fair bit of disease behind, it will progress if you are not keeping it in check. There is very little incentive to stop treatment in people who are in partial remission.
The question would be: How do we get people into complete remission and even potentially molecularly negative or minimal residual disease-negative so that we can stop treatment? This same type of thing is going on in CML [chronic myelogenous leukemia] now, which is further along, and in which we do see molecular remissions with the TKIs. There is a lot of interest in being able to stop therapy so patients don't have to keep taking the drug and experiencing even mild side effects, and because of the financial burden to society and the patient. Don't forget that we have copayments for these oral TKIs.
Dr. Cheson: These drugs are not like imatinib, dasatinib, and nilotinib. They are far from it. Most patients [on the kinase inhibitors] do not even have a complete response. What sorts of combinations would you like to use that you think would get you to that goal?
Dr. O'Brien: The combinations that people are most interested in are the ones that don't involve chemotherapy, to get rid of the chemotherapy-related side effects. Would I combine 2 B-cell receptor inhibitors? I think it's reasonable. Could you combine a B-cell receptor inhibitor with ABT199, the Bcl-2 inhibitor? That is very exciting, because now you are hitting 2 different pathways.
Dr. Cheson: Right.
Dr. O'Brien: Monoclonal antibodies have been used with these drugs. The nice thing about adding a monoclonal is that you very rapidly reduce the lymphocytosis so you get a faster response. We don't know yet whether you get a deeper, more durable response with the addition of a monoclonal.
Mixing and Matching Drugs
Dr. O'Brien: The strategy has to be combinations. If you are getting a partial remission with a single agent, it doesn't make much sense to stop the drug, because if you are leaving a fair bit of disease behind, it will progress if you are not keeping it in check. There is very little incentive to stop treatment in people who are in partial remission.
The question would be: How do we get people into complete remission and even potentially molecularly negative or minimal residual disease-negative so that we can stop treatment? This same type of thing is going on in CML [chronic myelogenous leukemia] now, which is further along, and in which we do see molecular remissions with the TKIs. There is a lot of interest in being able to stop therapy so patients don't have to keep taking the drug and experiencing even mild side effects, and because of the financial burden to society and the patient. Don't forget that we have copayments for these oral TKIs.
Dr. Cheson: These drugs are not like imatinib, dasatinib, and nilotinib. They are far from it. Most patients [on the kinase inhibitors] do not even have a complete response. What sorts of combinations would you like to use that you think would get you to that goal?
Dr. O'Brien: The combinations that people are most interested in are the ones that don't involve chemotherapy, to get rid of the chemotherapy-related side effects. Would I combine 2 B-cell receptor inhibitors? I think it's reasonable. Could you combine a B-cell receptor inhibitor with ABT199, the Bcl-2 inhibitor? That is very exciting, because now you are hitting 2 different pathways.
Dr. Cheson: Right.
Dr. O'Brien: Monoclonal antibodies have been used with these drugs. The nice thing about adding a monoclonal is that you very rapidly reduce the lymphocytosis so you get a faster response. We don't know yet whether you get a deeper, more durable response with the addition of a monoclonal.
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