Panelists:Rafael Bejar MD, PhD, UCSD Moores Cancer Center; Elias Jabbour, MD, MD Anderson Cancer Center; Rami S. Komrokji, MD, Moffitt Cancer Center; Ruben A. Mesa, MD, FACP, Mayo Clinic Cancer Center
Ruben A. Mesa, MD, FACP: There is a focus and excitement around immunotherapy to a degree that there hasn’t been in the past. And certainly in solid tumors, it has really been incredibly impactful in several diseases. What do you think, Elias, in terms of immunotherapy, cellular-based therapies, CAR T-cells, PD-1 inhibitors, where do they stand particularly in this subset of myeloid diseases like AML?
Elias Jabbour, MD: You know, we’re shifting our way of treatment from killing the cancer cell to harnessing the immune system that can go after the cancer cells. And the proof of evidence we have, for example, is in checkpoint inhibitors, where we know the cancer cell can suppress the immune system from exerting its role. The checkpoint inhibitors, PD-1 inhibitors, PD-L1, CTLA4 in melanoma, for example. In leukemia, we know in MDS, there’s overexpression of PD-1; and, therefore, trying to inhibit the suppression of the immune system can upregulate the T-cell function and kill the leukemic cells. It’s still too early.
People are calling us for immuno-oncology. It’s, like, fashionable now. Everybody wants to use immune therapy everywhere. It doesn’t work everywhere. We have multiple trials at MD Anderson in MDS patients who: fail on azacitidine or decitabine to be salvaged; or, up front, in combination in leukemia, unfit patients using nivolumab plus azacitidine; and even in patients who are young, to add nivolumab, which is a PD-1 inhibitor, to the standard backbone of chemotherapy.
I’m very cautious right now. I don’t have results to support it. We have the trials ongoing. Let’s wait until next year. The excitement is great, but I don’t think we have enough data to say immune therapy is ready for AML. The CAR T-cells are still at the early stage. In ALL, it works at the high price of safety concerns. The concern in AML is targeting the stem cell—going into aplasia that will never end—plus cytokine syndrome. So it’s still behind compared to ALL, although the University of Pennsylvania group are working on engineering the CAR T-cell for myeloid disorders.
Ruben A. Mesa, MD, FACP: I think you raised earlier this question of maintenance, and I think that they deserve exploration across the board. But when I think about the intensity of AML, do immune-based responses really fall best into areas where we have time? Where they’ve been cytoreduced? There’s a patient who approached me who had found this paper saying that avocadoes had an anti-leukemic effect and he had 50% blasts, and would that work? And I’m like, not all the guacamole in the world is going to put you in a CR with your acute leukemia. But if you had a low-intensity immune way to approach that group that have that high risk, that clearly might be of interest. Maybe even the interferons and other things that have improved their safety profile.
Rami Komrokji, MD: I think that the key point is where the immune therapy would fit. And I think, as you’re suggesting, maybe this is not an up front strategy. Maybe this is a maintenance strategy. We know that from the allogeneic stem cell transplant because it is a form of immune therapy. So maybe the patients that have minimal residual disease, as we talked about, those are the patients that benefit. As Elias nicely summarized, I think there are different venues. It’s definitely exciting. It opens a new venue to test for the patients. But they are not real-time ready for patients in clinical practice.
Elias Jabbour, MD: These options are being explored in maintenance strategy, like nivolumab single-agent in somebody who is high-risk or MRD-positive, getting nivolumab for a year. We’re using the monoclonal antibodies anti-CD123 as a maintenance strategy. Amgen has a program called BiTE: the T-cells and the myeloid cells are together. It may go to maintenance later on. And Seattle Genetics has antibodies, as well, being explored, too.
Rafael Bejar MD, PhD: The other potential role for these immune therapies—as you mentioned, the CAR T-cells—the risk is that you target a marker on the leukemia cells that’s also present on the normal stem cells. But this could be used as a bridge to transplant for patients that have no other mechanism to get there.
Transcript Edited for Clarity