ASCO Review: Lots of CAR-T Stuff

I had hoped to write something about what I learned on Day 3 of the ASCO conference, but I've been busy with work and I've barely had a chance to think about it. I did learn a lot that day, it had a lot to do with the place that patients have in the oncology community. I'll get to it.

For now, a quick look at one of the hot topics of the ASCO conference: CAR-T. There were dozens of presentations about various CAR-T treatments. Not all were about Follicular Lymphoma. But it's clear that CAR-T treatments are one of those approaches that oncologists are excited about, and are putting a lot of hope into.

(And looking back at what I write about day 1 and day 2 of the conference, it seems like most cancer folks are going with the "we should be excited!" approach to CAR-T form day 1, rather than the "we need to learn a lot more!" approach of day 2, which is interesting.)

So here's a quick run down of some more of the CAR-T stuff that came out of the ASCO conference (and this is just some, not all, by any means):

•  One of the ways around the high expense of CAR-T is by developing an "off the shelf" version. In other words, instead of a treatment that is made for each individual patient, there could be a version that works for everyone who wants it. Results of a phase 1 study trying to do that: "First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large B-cell or follicular lymphoma (R/R LBCL/FL): ALPHA study." In a very small study of DLBCL and aggressive FL patients, patients were first given a treatment to wipe out most of their existing T cells. Then they were give the "off the shelf" CAR-T. Like personalized CAR-T, this one targets lymphoma cells. But the pre-treatment makes sure that the patient's immune system doesn't get in the way of the new T cells as they go after cancer cells. The treatment was effective (9 patients were evaluated, with 3 Complete Responses and 4 Partial Responses, for a 78% response rate). As a phase 1 trial, safety is a primary concern, and it was shown to be safe, with expected side effects. 9 patients is very, very small, but the results are enough to continue on a larger group. Definitely worth watching.
• Most CAR-T treatments involve targeting of the CD19 protein on the cancer cells. Those kinds of targets are common -- Rituxan goes after the CD20 protein. While targeting CD19 seems effective, some researchers think it contributes to CAR-T being able to work well at first, but then stop working. One presentation, "Safety and efficacy of optimized tandem CD19/CD20 CAR-engineered T cells in patients with relapsed/refractory non-Hodgkin lymphoma," described a CAR-T treatment that targets both CD19 and CD20. Two targets might be better than one. The study described a combined phase 1/phase 2 trial with 99 patients with several different lymphomas, incuding some with FL and transformed FL. Overall, the early results look good, with 84% getting a response after a follow-up of 13.5 months, and the treatment being fairly safe. If the goal, though, is to produce longer responses than CAR-T with only one target, then longer-term follow up is going to be really important. Another one to keep an eye on.
• On the other hand, there was one study of long-term follow-up of CAR-T patients, called "Long-term follow-up of anti-CD19 CAR T-cell therapy for B-cell lymphoma and chronic lymphocytic leukemia." The study describes a group of patients who were given early versions of CAR-T treatment at the National Institute of Health between 2009 and 2015 -- 43 patients in all. They had a variety of lymphomas, including 5 with FL. The overall remission rate was 76%, with 54% complete remission and 22% partial. Long-term side-effects were minimal. Of the patients who had a CR, 15 of the 25 were still in remission. While the long-term effects for some patients were excellent (the FL patients did especially well), they were still limited -- close to the breakdown I have heard (1/3 of patients have a long remission, 1/3 have a shorter remission, and 1/3 have no remission). But these are also patients who had an early version of CAR-T, and the treatment does seem to be improving as researchers learn more from patients who have had some version of it.

Lots more for me to work through. I'll start getting at the non-CAR-T stuff soon. As interesting and promising as it is, there is also some good information about other treatments for Follicular Lymphoma.