Transcript:Ian W. Flinn, MD: We started off talking about Hodgkin’s disease, and we were talking a little bit about the differences in the microenvironment. But I think it’s important to spend a little more time on the trials in Hodgkin’s disease. Recently, we’ve seen the FDA approval of nivolumab for refractory Hodgkin’s disease. Can you talk about that?
Andre Goy, MD, MS: Sure. As I mentioned, there was a signal early on in a phase I trial, across the board in non-Hodgkin lymphoma—but, at the same time, in Hodgkin, it clearly appeared on a small number of patients, 25 patients—that was published in New England Journal of Medicine, where the response rate was 87%. And patients were treated until they achieved a CR, or had toxicity, or stopped the treatment. They were not treated indefinitely, and some of these patients have remained in remission up to 2 years. Close to 20% of them were in CR. So, this was really remarkable in a heavily pretreated population that is not necessarily a candidate for allogeneic transplant or has any other option. Most of them had failed prior brentuximab. This is clearly something that was such a strong signal, and we see more and more approvals in the field of oncology and hematologic malignancies; getting drugs approved early based on phase II data because the signal is so strong.
Ian W. Flinn, MD: Did that surprise you? It surprised me. With that patient population, I would not have thought that an immunotherapy would have so much success. We think of all the therapy these patients get. It’s directed at the lymphoid space, is very lymphoid-depleting, yet, it’s still effective.
Andre Goy, MD, MS: It’s interesting what’s happening in Hodgkin lymphoma. You’re right, but when you think about it, patients with Hodgkin lymphoma can be severely immunosuppressed—but their microenvironment is very peculiar. They have very few tumor cells, Reed-Sternberg cells, particularly at the beginning. Over time, they have more, but you have this whole infiltrate that varies from mostly a T-cell infiltrate or mixed B and T cells that are essentially there to promote the tumor cells. And so having a way to try to navigate this infiltrate and direct them against the Reed-Sternberg cells, it was not necessarily predictable, but very impressive and makes cellular sense.
Krishna V. Komanduri, MD: Let me just add to that. I think, with respect to knowledge gaps, it’s very exciting to see that we saw these responses in melanoma and lung cancer. And then we’re really starting to see the growth of this correlative scientific understanding of what is the composition and what predictors happen. In Hodgkin’s disease and lymphomas, in particular, in that initial biopsy of lymph node, we have the ability to really characterize how that tumor microenvironment is assessed on a cellular level and how it will predict responses. And we haven’t really seen those detailed analyses coming out, but I think when that happens, that’s inevitable with all the exciting clinical trial activity. It will really help us to guide predictors of response.
Andre Goy, MD, MS: It’s a very exciting field in Hodgkin lymphoma that hasn’t seen a new drug for decades, and then all of a sudden we have brentuximab approved recently—that is an anti-CD30 antibody drug conjugate with impressive activity, and it has now moved into the frontline combination. But having checkpoint inhibitors, I think the future is really exciting. For example, we actually have an ongoing trial that is nivolumab plus rituximab in patients who are not candidates for standard chemotherapy, elderly patients, and I think we really are going to see an interesting shift on how we treat those patients. And we know Hodgkin typically does well with ABVD (Adriamycin, bleomycin, vinblastine sulfate, and dacarbazine), but there’s a fraction of 10%, 15% of patients who are very refractory, so this is great to have a new tool.
Frederick L. Locke, MD: And I think it’s important that we take a step back. Hodgkin’s disease, it makes sense, based upon the preclinical data, that patients respond based upon that 9p24.1 amplification, which drives PD ligand 1 and PD ligand 2. That amplification also drives JAK2 expression, which also increases PD ligand 1 expression. So, it makes sense for Hodgkin’s, and that rationale can’t necessarily be applied to the other hematologic malignancies. And, as we’ve seen with single-agent checkpoint inhibitors, the response rates aren’t as good for follicular lymphoma and diffuse large B-cell lymphoma. I’d also point out with multiple myeloma, as a single agent, that with antibodies against PD-1, there’s really no response.
Transcript Edited for Clarity