Bi-Specific CAR-T

I don't usually pay as much attention to what happens at the AACR (American Association for Cancer Research) when it happens in the spring, at least compared to ASCO. It's a busy time for me. But I do see news from the conference, and this one is worth sharing. 

The news article I saw is called "Bispecific CAR T-Cell Therapy Has “Robust” Activity in Non-Hodgkin Lymphoma." A bispecific and a CAR-T in one? The two hotest treatments in the Lymphoma world combined? Sounds good to me.

It's not exactly a combination of, say, the bispecific Mosunetuzumab and the CAR-T Kymriah. But it does combine the two ideas. The treatment described in the article is a CAR-T, so it involves changing a patient's T cells so they recognize lymphoma cells. The bi-specific part comes because they are changed to recognize two different proteins on those cells -- CD20 and CD19. Both are very common on B Lymphocytes (the type of white blood cell that turns cancerous in Follicular Lymphoma and many other Lymphomas).

This research involves a phase 1 clinical trial (you can see the details of the trial here), so its main purpose is to measure safety -- how much of the treatment can be given to remain safe while still being effective. The researchers hope to have 24 patients in the trial, and they report here on the first 11. Four of them have Follicular Lymphoma, and the rest have other types of lymphoma. All had already had at least 2 lines of treatment before this one.

Patients were first given traditional chemotherapy, and the bi-specific CAR-T, tryi ng two different doses. Results look good. Combing the results from the two different doses, the Overall Response Rate was 91% (10 out of the 11), and the Complete Response Rate was 73%. The patients who received the higher dose had a 100% CR and the lower dose had a 63% CR. After 21 months, the median PFS was 18 months.

The bigger issue is safety -- how are the side effects?

There were certainly some to be found. All patients reported anemia (low red blood cells). 10 of the 11 had neutropenia (low white blood cells), and thrombocytopenia (low platelets). There was one case of  grade 5 (very high) hypocellular marrow (fewer than normal bone marrow cells). There were no cases of damage. Six patients had low level Cytokine Release Syndrome (CRS), all of which were controlled by medication. 

That all seems promising to me.  I would have expected more problems with side effects, given the chemo at the beginning of the process. Of course, this is a very small number of patients, so a larger phase 2 trial might show more of them, or lower effectiveness.

But it's promising. I wrote a couple of months ago about the different directions that researchers were going with CAR-T treatments, and this is just another example of how that kind of treatment might change and improve over time.

As always, there's lots to be hopeful about.