Andre Goy, MD
Exciting developments in the treatment of patients with lymphoma were highlighted at the 2018 ASCO Annual Meeting, said Andre Goy, MD, holding out the possibility of treating patients without chemotherapy and even treatment-free remission.
“That would be fantastic,” he said. “Obviously, that would be the goal.”
Novel chemotherapy regimens, and the increasing use of chimeric antigen receptor (CAR) T-cell therapy and immunotherapy are opening up new possibilities for helping patients with lymphoma live longer, healthier lives, even those who had poor prognoses just a few years ago.
In an interview with OncLive
, Goy, chairman and director, chief of Lymphoma, and director of Clinical and Translational Cancer Research at John Theurer Cancer Center, discussed some of the most important lymphoma data presented at the 2018 ASCO Annual Meeting and potential future directions for treatment.
OncLive: What were some of the highlights of this year’s ASCO Annual Meeting?
Five years ago, we did not think that immunotherapy would be where it is now. This was one of the first topics that is all over ASCO and is changing the field.
Obviously, the CAR T cells in lymphoma was recognized as the most significant advance by ASCO in 2018. There were several data [presented] at this year’s meeting in aggressive lymphoma. First, there was an update on duration of response from the ZUMA-1 trial. The take-home message was that it was more than 100 patients in the trial with relapsed/refractory lymphoma after at least 2 lines of therapy. This was a heavily pretreated population, and what was interesting was that the response rate was over 80% and the complete response (CR) rate over 50%.
The other interesting thing was that the response at 3 months is very predictive of outcomes. In other words, if a patient achieved a CR, many of them remained in CR. Also, some of these patients in partial response (PR) can convert into CR early in the process.
In some of these patients, there was evidence that there were persistent CAR T cells, but it's not necessary. Overall at 15 months, 59% of patients are still doing very well and in remission. That's quite remarkable in a population that would have no option otherwise.
The question becomes, “What can we do to try to predict this?” We don't have a good way to predict except we know that the area under the curve on the lymphocyte amplification is really what predicts the outcome in those patients. We are learning how to mitigate the side effects better with earlier intervention with tocilizumab (Actemra) anti–IL-6 agents and corticosteroids, and neither of them affect response, which is very critical.
We are starting to learn some factors that predict toxicity. Particularly in cytokine release syndrome (CRS) and neurotoxicity. Again, the amplification of the T cells correlates with neurotoxicity and correlates with response. The CRS does not. CRS starts around 3 to 5 days and the neurotoxicity starts around 5 to 10 days. We see the tumor burden and the inflammatory status at baseline is somewhat difficult to quantify; however, it's interesting because as we learn going forward, maybe there is a benefit to try to debulk these patients or try to bring CAR T cells in earlier in the process.
There are data that were published in CLL showing that the number of prior therapies, exposure to fludarabine-like agents, has an impact on the functional ability of those T cells to expand.
We are starting to dissect all of this and understand how we're going to build up. What is quite remarkable in the ZUMA-1 trial, and in other CAR T-cell therapies, the number of prior therapies does not affect the response.
There were also data presented from the TRANSCEND trial on JCAR017, and it was really interesting that it did as well as it did because there seems to be a little bit less CRS and it seems to be more durable and effective as an outpatient [treatment]. In a higher-dose cohort, their CR is in a high of 40% and a response rate around 80%. And that is, again, regardless of prior therapy.
What other research in lymphoma are you excited about?
There are ongoing studies; there are actually more than 300 studies in the United Studies and 300 in China and Europe in CAR T-cell therapies and combinations with checkpoint inhibitors, to see how we can build up these combinations. It is very exciting.
In terms of immunotherapy, there was also the first presentation of an anti-CD47, which is a macrophage checkpoint inhibitor. That was done in combination with rituximab (Rituxan). It's early, a small study, but a proof-of-concept trial that some macrophages are very important and that's another area that will be very promising in the future.