Owen A. O’Connor, MD, PhD, outlines the importance of clinical trials and reviewed strides made in lymphoma treatments.
At the American Society of Clinical Oncology (ASCO) 2018 annual meeting in Chicago, Illinois, Rare Disease Report® sat down and spoke with Owen A. O’Connor, MD, PhD, director of the Center for Lymphoid Malignancies at Columbia University. In the exclusive interview, Dr O’Connor outlined the importance of clinical trials and they key role they play in developing new and effective treatments in the landscape of lymphomas. He also provided additional insight into recent strides made in lymphoma treatments.
Interview Transcript (modified slightly for readability):
Dr O’Connor: The team approach can be interpreted as teams of clinicians around the world that specialize in seeing patients, working together, and putting them on trials, but it doesn’t intend to dismiss the importance of translational scientists and basic scientists. If we’re going to take the approach that we’re going to start from scratch, look for new drugs, and explore the merits of combinations, I wholeheartedly believe that needs to start in the laboratory.
We need to be able to vet these combinations in reasonable, surrogate models of the disease, then identify those combinations that have the greatest potential, and then translate those models to the clinic.
When we move to the clinic, we also really need to focus on understanding the pharmacology of these drugs and how we think they’re working [and the] the context in which they are working. For example, [we need to ask questions like] are they working in this mutation, or that mutation, this immunophenotype, [or] that immunophenotype?
That [process] requires us to go from the lab to the clinic, but it’s just as important to take that information from those trials and do those correlative studies that take us back to the lab where we can add additional color on the exact molecular subtype of lymphoma these patients have. [This will help us] try to identify a particular biological context where these regimens might work better or not as well.
It is incredibly rewarding to be able to give and develop a drug in the laboratory [because you are able to] study it in the laboratory, garnish as much insight into its mechanism as you can, and then study those effects in en vivo models.
There’s few things as exciting as giving a brand-new drug to a human patient who’s never seen that drug before. Trying to really focus on the best way to give those drugs, making sure—of course—it’s always safe first, and then optimizing pharmacokinetics, pharmacodynamics, and other pharmacologic parameters to make sure we get that part right before we move into the phase 2 [is important].
The translational piece, how we move to the clinic; the phase 1 piece, how we optimize the pharmacologic properties of the drug; the phase 2 piece, how we identify the patient population within which we believe the drug is to have the greatest clinical benefit; and then moving into the regulatory piece [are all part of the process.] How you think about the approval of a drug in T-cell lymphoma, mantle cell lymphoma, or cutaneous t-cell lymphoma in the context of the current landscape of drugs that are out there is interesting and challenging, and it’s always evolving.
We’ve now been able to get many drugs approved in mantle cell lymphoma. Since bortezomib, we now have lenalidomide and [Bruton's tyrosine kinase] BTK inhibitors in mantle cell lymphoma, and we’ve changed the natural history of that disease with new drugs.
In [peripheral T-cell lymphoma] PTCL, I’m certain we’re on the verge of doing the same thing with a whole host of new drugs. That dynamic changes as we approve drugs in the space. What a regulatory study looks like in 2018 and 2019 may not be what it would have look like in 2010 or 2013. Trying to have some foresight about what that regulatory study looks like, trying to think about the landscape and defining that patient population as precisely as you can is critical to the regulatory success.