INTERVIEW WITH THE INNOVATORS
proliferation and expansion in the body and provides a survival signal to these T cells that allowed them to survive at relatively high levels for very long periods, and this really has not been seen with genetically modified cell therapy in prior trials. PMO So there is a pull-through/push-through process between the technology and the drug development: technology making possible drug development, and drug development suggesting new ways to refine technology. Is this a good way to view the process? Dr Porter Absolutely – that’s the dynamic interplay we’re benefitting from. PMO How will this redefine the hierarchy of treatments for CLL and ALL?
“Our hope is that this might be a one-time therapy as opposed to a medication that one might have to take for life.” – David L. Porter, MD Dr Porter I think in CLL this is a completely new modality. There are a lot of new and different therapies being developed for CLL. I think it’s very early to know where this might fit in with all the newer biological agents, but it is a completely new, very personalized approach. While it is too early to know, our hope is that this might be a one-time therapy as opposed to a medication that one might have to take for life, for instance. PMO You hope it will be a once-and-done process? Dr Porter It may be a once and done, but this will be determined in long-term follow-up. That is the intent, in any case. Whether that proves to be true, we don’t know yet. At this point, CTL019 has been limited to patients with multiple relapsed/refractory CLL, offering them a completely new approach that has shown significant response rates. PMO When will CTL019 be nudged into earlier usage? How long do you think it should be held in reserve before it is used? Dr Porter I think that given these kinds of results, and as we learn more about the short- and long-term stage usage, it is absolutely reasonable to think about moving this kind of therapy earlier in the course of disease before patients are highly refractory – before they have extensive, bulky disease. We have some preliminary evidence that the side effects may be less if they have less leukemia, and all of that lends some support to explore using this earlier in the course of their disease. PMO What are the plans for continuing research, and what is the scenario for patient access to this treat-
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ment in terms of where and when it will be available to all patients who need it? Dr Porter We are now considering doing a larger multicenter trial. Right now our specific therapy is only at the University of Pennsylvania, though there are other centers with similar types of therapy. The CTL019 cell technology has been licensed by Novartis. We all hope to be able to manufacture this in large scale: they like to say not scale up but scale out. Each product is made for an individual patient, and we believe there will be facilities and strategies to be able to make these cells, so this could be available really in a relatively short time frame to people all over the country and, in fact, all over the world. PMO You have given us incredible clarity on the results, nature, and future of CTL019. To complete the picture, I was wondering if you might suggest any lessons that this discovery holds for the practicing hematologist or oncologist at this point in time, both biologically and empirically. By biologically, I mean what lessons could they learn in terms of how they can familiarize themselves with disease pathophysiology to help them appreciate what this is doing, and what they should know to understand how it is so personal in the way each patient responds to it; and empirically, what lessons are there for them to revise their treatment strategies for ALL and CLL. Dr Porter Biologically, one needs to understand that this therapy is targeted against a specific protein, so it is only effective if the cell has CD19. It’s biologically then expected that it results in B-cell aplasia, so these patients lose their B cells. Physicians have to be aware of that and learn how to manage that as a side effect. But it is also important to think that once we understand the biology of the cancer and identify unique molecules on the cancer surface, then this kind of technology can be applied not just for CLL or ALL but for other tumor types as well, and there is the potential for this to be a generalizable modality of cancer therapy in the future. In terms of empiric lessons, I think mostly it’s impor tant to understand this is still in the early stages of testing. There are a number of side effects that may require some specialized management, but as we treat more and more patients and disseminate this into multicenter clinical trials, there will be much more information about anticipated side effects and toxicity management, so that we can envision this therapy being applicable truly to patients all over the country if not all over the world. PMO Thank you for sharing this extraordinary personalized medicine experience with CTL019. We will be looking forward to its continued movement through the research and development cycle and wish you and the entire research team continued success. Dr Porter Thank you. u
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May 2014
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Vol 3, No 3