Novel Agents: Making the Benefit Last in CLL
Novel Agents: Making the Benefit Last in CLL
Dr. Cheson: Another one of the agents -- ABT199 -- seems to be equally exciting.
Dr. O'Brien: I think so too. The responses are very fast. Of interest, something you see with ABT199 that you don't necessarily see with the B-cell receptor inhibitors is very early bone marrow responses. Will that translate into a reasonable complete remission rate? We don't tend to see that with the other drugs. It remains to be seen, because the follow-up is short.
The patterns of how these drugs work is a little bit different. We know that in patients with CLL, with the B-cell receptor inhibitors, initially we see very dramatic shrinkage in the lymph nodes and at the same time the lymphocyte count goes up. That is obviously very different from what we see with chemotherapy or antibodies, and very early in the trials, some of the patients were taken off the study because it was naturally assumed that they were progressing. Then it became apparent that that was not what was going on. The lymphocyte levels [initially] go up, and then over time (in most patients but not all) they reduce. There are some interesting explanations for why this is happening. A lot of it comes from Jan Berger's lab in terms of alterations in chemokines that cause the cells to adhere or chemotax to the stroma. It is important to recognize that this is the pattern of response with these drugs, because if you are not familiar with that, you may think initially that a patient is progressing. The good news is that most people with CLL can walk around with fairly high lymphocyte counts and be asymptomatic.
Dr. Cheson: You alluded to the fact that unless you use these drugs, you have no idea how really exciting they are. Patients come in with huge masses and they are gone within a day or two, and they feel better. It's amazing.
However, a problem with these drugs is that you have to keep taking them. They aren't going to be cheap, and right now patients have to take them forever. We have had a few patients on idelalisib whose liver enzymes increased and we had to hold off on the drug. Within days the nodes come back, and everything goes south a bit. Is there a strategy that you can foresee that would obviate the necessity of taking these drugs forever?
Now You See CLL, Now You Don't
Dr. Cheson: Another one of the agents -- ABT199 -- seems to be equally exciting.
Dr. O'Brien: I think so too. The responses are very fast. Of interest, something you see with ABT199 that you don't necessarily see with the B-cell receptor inhibitors is very early bone marrow responses. Will that translate into a reasonable complete remission rate? We don't tend to see that with the other drugs. It remains to be seen, because the follow-up is short.
The patterns of how these drugs work is a little bit different. We know that in patients with CLL, with the B-cell receptor inhibitors, initially we see very dramatic shrinkage in the lymph nodes and at the same time the lymphocyte count goes up. That is obviously very different from what we see with chemotherapy or antibodies, and very early in the trials, some of the patients were taken off the study because it was naturally assumed that they were progressing. Then it became apparent that that was not what was going on. The lymphocyte levels [initially] go up, and then over time (in most patients but not all) they reduce. There are some interesting explanations for why this is happening. A lot of it comes from Jan Berger's lab in terms of alterations in chemokines that cause the cells to adhere or chemotax to the stroma. It is important to recognize that this is the pattern of response with these drugs, because if you are not familiar with that, you may think initially that a patient is progressing. The good news is that most people with CLL can walk around with fairly high lymphocyte counts and be asymptomatic.
Dr. Cheson: You alluded to the fact that unless you use these drugs, you have no idea how really exciting they are. Patients come in with huge masses and they are gone within a day or two, and they feel better. It's amazing.
However, a problem with these drugs is that you have to keep taking them. They aren't going to be cheap, and right now patients have to take them forever. We have had a few patients on idelalisib whose liver enzymes increased and we had to hold off on the drug. Within days the nodes come back, and everything goes south a bit. Is there a strategy that you can foresee that would obviate the necessity of taking these drugs forever?
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