Where Immuno-Oncology Is Heading

Transcript:Ian W. Flinn, MD: Krishna, this has been a session on immunotherapies for lymphoid malignancies. So, I want you to look into your crystal ball and in 5, 10 years from now, do you think we’re still going to be giving patients with low-grade lymphoma bendamustine as a frontline therapy? Do you think we’re at the edge where we can start replacing these DNA damaging agents?

Krishna V. Komanduri, MD: I think before we get too self-assured we have to point out that in a group of diseases that we’re talking about, lymphoid malignancies, we know the most about surface antigens. And we also have a relatively easily targetable set of antigens that, in some cases, we can live without because we can live without healthy counterparts. So, I do think that this is a space that the role of chemotherapy is likely to be minimized, really, because of the success of immunotherapy. And I do think that there are paradigms for other disease states, whether it be myeloid malignances or solid tumors where this will be the tip of the spear.

I don’t know that I want to go as far as to say we wouldn’t be using conventional cytotoxic agents, but I think that this is an area where it has really been a long time. Ron Levy has commented that he would go to a SITC meeting or an immunotherapy plenary session at a national oncology or hematology meeting. You might have half of the seats in the room empty and not a lot of people coming to the microphone afterward, and now they’re all standing rooms only. So, for me, for somebody who has been in T-cell immunology for 20 years, it’s extraordinarily exciting. I hope that we get to the point where we not only have really successful immunotherapies, but they’re less toxic. Because, in some cases, the immunotherapies do have toxicities that rival chemotherapy. I’m very optimistic though.

Ian W. Flinn, MD: I guess one of the challenges that we’ve been seeing recently in the treatment of B-cell malignancies with the B-cell receptor pathway drugs is that it’s a paradigm of continual therapy for patients. A lot of the things that we’re talking about now with the immunotherapies, it’s less of that. It’s more of an episode of treatment and get people off. That has a certain appeal to it. Andre, what do you think?

Andre Goy, MD, MS: I think it’s a very good point. Summarizing, this was a great session. I think we believe we are at the tipping point in oncology and hematologic malignancies. It’s the most exciting time to be in what we do, there’s no question about this. The pipeline in oncology represents two-thirds of the pipeline of medicine, and you alluded to the BCR-targeting agent. We think of immunotherapy. We just have this perfect amazing environment to have all these immunotherapy tools, but we also have all those small molecules, so a combination of those will be really interesting. And that creates even more possibilities. I think in the “collective wisdom,” which is the theme of ASCO this year, it’s important that we think about the big picture—because we have so many options.

And the reality is that some of these treatments, as you mentioned, have to last for years until progression. Some patients are on BCR-targeted therapy and have been on treatment for 4 or 5 years. I think this is amazing, particularly in 17p-deleted disease, etc. But at the same time, we need to look at how, as a society, we’re going to be reasonably able to try to pick the best option. I think we have developed an effort in our institution with an outcome database that functions like a GPS of cancer. So, we have digitized all the phenotypes of the situation at baseline, and we can extract data from the EMR to try to identify what was the journey of the patient by reducing the biological variance to try to identify patients that have similarities.

For example, in breast cancer, we have 3800 different situations. In reality, 22 of them represent 90% of the patients. It’s really important because we put this against our database of patients and try to sort it out. The NCCN has started an effort to try to implement their block system, where they try to rank all the options because of the situations we face. We are subspecialized, but to our audience that may practice general oncology, this is getting very confusing. We have a huge menu, a big pipeline, and not enough patients on clinical trials. So, I think we really need to work together and try to understand in a bigger picture—again, for the benefit of our society—what are the best options and what is the impact of the sequence of treatment. And I think that’s going to be really important, and the cost, as well.

Ian W. Flinn, MD: Yes. I think that was well said. There are a lot of challenges ahead, but a lot of opportunity, as well. Thank you. Well, this has been extremely informative. Before we end this session, I’d like to get final thoughts from each of our panelists. Any added thoughts to what we’ve been discussing?

Krishna V. Komanduri, MD: No. I think it’s, to me, both as an oncologist as a scientist, very gratifying. I have great optimism, and I’m excited about all the things, to answer the questions that Andre and others have posed.

Andre Goy, MD, MS: I think it was great. I think there is palpable enthusiasm in the field of oncology, and we’re lucky we can have so many changes in our lifetime in oncology. I think we are at the tipping point, and it’s wonderful.

Frederick L. Locke, MD: Yes. This is an amazing time. I’m really excited to be a part of it. I think there’s great excitement about CAR-T cells, TCRs, and adoptive transfer of autologous cell products as therapy for hematologic malignancies and lymphoid cancers. And I think checkpoint blockade has significant promise, as well. So, it’s really an exciting time, and I’m happy to be a part of it. It’s great for our patients, too.

Ian W. Flinn, MD: It sure is. Well, thanks to all of you for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you find this Peer Exchange discussion to be useful and informative.

Transcript Edited for Clarity