Follicular Lymphoma Approvals and Trials at ASH

Hello all. 

This is probably my last post for 2022, so I was looking for something appropriately "end of the year"-themed. I couldn't find anything like that, and I don't have time to come up with my own Top 10 list, so I'll offer two things that I think kind of sum up The Year in Follicular Lymphoma.

The first is a quick screenshot from the FDA list of approvals in oncology for the year. There were two FDA approvals in 2022 for Follicular Lymphoma: 

In case that's hard to read, the approvals were for 1) Tisagenlecleucel (also known as Kymriah), a CAR-T treatment approved for patients with Relapsed/Refractory FL who have already had at least two treatments, and 2) Mosunetuzumab (also known as Lunsumio), a bispecific that is also approved for patients with Relapsed/Refractory FL who have already had at least two treatments.

That seems appropriate -- two approvals, one for CAR-T and the other for a bispecific. Those seem to be the two treatment categories that have created the most excitement among Lymphoma experts over the last year. They are both very effective and fairly safe, and move us even further away from traditional chemotherapy (though chemo still has a place for many FL patients, and will for a while). 

So that's a good way to end the year -- looking back at the success that researchers have had in changing the way patients are (and will be) treated.

The second things I want to share is one more look back at ASH. This one is from the website Cancer Therapy Advisor, called "ASH 2022: Trials Show Promising Results in Follicular Lymphoma." It highlights four clinical trials that had results presented at ASH this month. 

Interestingly, the first two trials that I already wrote about: one that showed that Rituxan by itself or with maintenance can give some FL patients a long time until next treatment, and one on the bispecific Odronextamab, which had excellent effectiveness, but raised some questions about safety.

The third one highlighted in the article looks at trial results for Tisagenlecleucel (also known as Kymriah), the CAR-T treatment approved earlier this year. This ASH presentation gave some updated results. The original trial report showed that the overall response rate (ORR) was 86%, and the complete response (CR) rate was 69%. The follow-up showed that it remained effective over a longer-term, with Progression-Free Survival at 67% and Overall Survival at 95% at 12 months, and the PFS rate of 57%, and the OS rate was 88%, after 24 months. 

Interestingly, the article includes an interview with an oncologist who says that we likely won't see CAR-T used in a community setting for 10 more years. In other words, patients will have to go to a hospital for CAR-T treatment, rather than going to an oncologist's office, the way some patients can for chemo, or Rituxan, or even bispecifics. There are still just to many risks involved with things like Cytokine Release Syndrome to administer CAR-T outside of a hospital, where such problems can be handled quickly. 

The fourth presentation is for a "triplet" -- a combination of three treatments. Combinations often have good effectiveness (since they usually come at the cancer in three different ways), but often have safety issues (since the side effects from three treatments can pile up and be three times as bad).

This triplet involves Polatuzumab, Obinutuzumab, and Lenalidomide. Obinutuzumab is a momoclonal antibody, used as an alternatuve to Rtuxan. Lenalidomide is also known as Revlimid, and is part of the R-Squared combination. 

Polatuzumab is less commonly used in Follicular Lymphoma. It's classified as an antibody-drug conjugate. It's like Rituxan, in that it attaches to a protein on the surface of a B cell. But it also has a bit of chemotherapy attached to it as well, so it can deliver the chemo directly to the cancer cell (like the way Zevalin delivers radiation, or a bispecific delivers a T cell). 

This triplet is effective and durable. The PFS rate was 83.3% at 12 months, 67.4% at 24 months, 64.6% at 36 months, and 53.4% at 48 months. The median Overall Survival was not reached. Safety is a concern (as it often is with triple combinations). 86% of patients had a grade 3 or higher Adverse Event (a serious side effect), with 3 fatalities. Most patients (77%) had a side effect serous enough to lead to stop treatment temporarily, and 34% had one that led to stopping permanently.

The researchers seem to think that this combination would do well in a larger study, with one commentator suggesting it could be directly compared to R-Squared in a randomized trial.

So there we are, at the end of 2022: lots of promise from some new treatments, lots of refinements to the treatments we already have, and lots of possibilities for the future.

Progress seems slow sometimes, but I continue to think that we're in a good place as FL patients, especially compared to where we were just a few years ago.

My plan for 2023 is to continue to do what I've been doing, keeping up with news in the world of Lymphoma and sharing what I learned. My 15th diagnosiversary is coming up just a few weeks. I'll have some things to say on that day.

I hope everyone has a happy and healthy end to 2022, and a good start to 2023.