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[Newer treatments] are definitely being used in the relapse population, and that’s where they made their mark like most other investigational agents for other cancers. I think the issue is that the response rate with initial induction therapy is so high. Whether or not there is going to be a maintenance-type study strategy, that’s a question with some of these therapies that are relatively low toxicity, but when you have a complete remission rate of 90-95%, and ALL’s not the most common disease – it’s a pretty rare cancer actually – that it’s going to be difficult to do large studies for indications in the randomized setting.
[Newer treatments] are definitely being used in the relapse population, and that’s where they made their mark like most other investigational agents for other cancers. I think the issue is that the response rate with initial induction therapy is so high. Whether or not there is going to be a maintenance-type study strategy, that’s a question with some of these therapies that are relatively low toxicity, but when you have a complete remission rate of 90-95%, and ALL’s not the most common disease – it’s a pretty rare cancer actually – that it’s going to be difficult to do large studies for indications in the randomized setting.
I think for ALL, [CAR-T therapies] are very effective. For other B-cell malignancies, I think the jury’s still out. There is exciting signal of efficacy but the treatment is not without cost. One, monetary cost. Two, the ability to make a biologic product in a timely fashion, to be able to deliver it, and three, toxicity associated with it. I think for ALL, given the response rates in the relapse/refractory setting, it’s a home run, because the bar previously was… blinatumomab with the CR rate of less than 40%, I believe. Before that, drugs like clofarabine with a 20-30% response rate. So, I think it’s been a complete home run. Obviously, the response rates in the current studies are greater than 50% and more so approaching 70-80+%, the complete remission rate. I think that’s a success that you can put a stamp on.
I think you’re going to lose patients [for CAR-T therapies]. I think there are patients that just can’t wait. There are single-agent drug studies at our center. I sit on the lymphoma DMT service where patients can’t wait a week just to get whatever they need for the study. To wait a month . . . you’re selecting patients that have more indolently growing disease, even though it could be, quote unquote, DLBCL or whatever. I think intention to treat, which is the pure way to do a study, I think that the data would become a lot more sobering.
The blood pressure part of the CRS [associated with CAR-Ts] easy to manage. The neurotoxicity is unpredictable and can be variable. Typically it’s reversible, but there are anecdotes out there of people that just haven’t recovered.
If anybody claims to know the pathophysiology of the neurotoxicity, they don’t, because nobody knows it. We know it’s not antigen. Whether it’s related to cytokines that get sequestered and trapped within the cerebral spinal fluid space, maybe. No one knows. Some people think IL6 inhibition actually makes it worse. I’m not sure. We just don’t know. It doesn’t seem to correlate with people that had previous central nervous system disease. If you look across all the histologies, and it’s a unique complication.
The next step is to study the PD-1s in combination. I think a lot of people don’t believe it’s going to be single agent-type stuff in the heme malignancies but in combination with things like kinase inhibitors, or lenalidomide, rational design, follicular lymphomas and indolent non-Hodgkin lymphoma that appears to be immune sensitive. Now, whether or not there’s going to be a strong signal with the PD-1s I think would be a question. In other diseases like DLBCL and T-cell histologies, it’s unlikely to be a home run, and it may just die in that space, actually.
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