CAR-T versus Immunotherapies in Lymphoma

ASCO Post has another video from the 2021 Pan Pacific Lymphoma Conference took place in Hawaii last month. This is a discussion between Lymphoma two experts, Dr. Bruce Cheson and Dr. Stephen Ansell. (If you've been reading a while, you now how fond I am of Dr. Cheson.) 

The video clip is called "Bruce D. Cheson, MD, and Stephen M. Ansell, MD, PhD, on Non-Hodgkin and Follicular Lymphomas: Integrating Non–CAR T-Based Treatments." 

Basically, as Dr. Ansell says, the Lymphoma treatment landscape seems to be about "drugs versus cells." On the one hand, there is lots of excitement about CAR-T (that's the "cells" part of this discussion), but also lots of alternatives that are worth being excited about, too (the "drugs" part).

Dr. Ansell points out that Dr. Cheson has spent lots of his long career as a cancer researcher looking at Immunotherapies and other non-chemotherapy options for lymphoma. He asks, where is the place for CAR-T in all of that?

Dr. Cheson points out some of the problems he sees with trying to make CAR-T the default treatment for lymphoma. For one thing, there us geography. There are very few CAR-T treatment centers in the United States that are easy to get to for most people. (He says about 75% of the patients in the U.S. would have a hard time traveling to a CAR-T center). It's also expensive. And while the data about its effectiveness looks good, it's worth taking a closer look.

For example, for patients who are not eligible for clinical trials, the numbers show that CAR-T is about half as effective as for people who are in clinical trials. (To make that clear: sometimes trials will reject patients who have health issues that might mess with the data. Someone might have heart problems, and if they died of a heart issue during the trial, it still cunts toward the Overall Survival statistics for the trial, since OS measures overall survival, not survival related to cancer. So, ironically, healthy people sometimes have an easier time getting into trials, especially phase 2 and 3 trials.)

Dr. Ansell points out that this is probably true of any treatment, not just CAR-T. In the real world, people have health issues that might make a treatment less effective.

Dr. Cheson then turns to the ZUMA-1 trial to make his point about drugs versus cells. The ZUMA-1 trial was the clinical trial that resulted in the first CAR-T approval for aggressive lymphomas. As great as the results were, Dr. Cheson points out the the 5 year Progression Free Survival for that trial was about 31%, and the 4 year PFS was 35%. Still good numbers. But a different treatment combination (a "drug"), Tafasitamab + Lenalidomide, had a very similar (34%) PFS at 4 years. For Dr. Cheson, that drug combo would be a much easier choice for many patients -- a monoclonal antibody and a daily pill, instead of travel to a CAR-T center and great expense for the "cell" treatment.

(If you're not familiar with the combo, Tafasitamab/Lenalidomide was approved for relapsed or refractory diffuse large B-cell lymphoma, including transformed FL, last summer. It's in a trial for Follicular Lymphoma, but no results yet.)

Dr. Cheson admits that, if a patients came to him very excited about CAR-T, was willing and able to travel and afford the treatment, he would certainly recommend it. He's not anti-CAR-T by any means. But he also thinks that a patient in that situation would be likely to do just as well with the other combo, without the hassle. 

He also mentions that there are a number of other promising treatments in the pipeline that may challenge CAR-T, including several bispecifics.

The upside to it all is that, as both of these experts agree, things are evolving fast -- there are lots of new and exciting treatments coming our way. We're still learning about the genetics of Follicular Lymphoma, and the more we learn, the more researchers will be able to target those cancer cells effectively.

As much as they seem to be "debating" these two choices, they also are clear that both are great choices for certain patients, and we'll have more great choices in the future.

I'll add this -- with the choices we have, and knowing that some will work better than others for certain patients, it's important to get second opinions when we can, especially from lymphoma experts. General oncologists can be great, but a specialist might see something that makes them think that a newer treatment might be especially effective, something a general oncologist might miss.

Lots to be hopeful for. Watch the video if you can (and, again, sorry -- there's no transcript for translating. But you might enjoy the Hawaiian music at the beginning, anyway).