Wednesday, November 27, 2024

ASH Preview: A "Triumph" for Tafasitamab

OK, this next ASH preview is an interesting one, not just because of the content of the presentation, but also the situation surrounding it. 

The presentation is called "LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: Results from a Phase 3 Study (inMIND)." The "LBA-1" means "Late Breaking Abstract," one that was added very recently, so it's not part of the regular numbering system.  

The abstract describes a very successful phase 3 clinical trial in which Tafasitamab, a monoclonal antibody, was added to the already well-known combination known as R-squared (Revlimid and Rituxan). An article on the Fierce Pharma web site says it "triumphs," which is why I used that word in my title for this post. It will likely go to the FDA for approval as a treatment for relapsed/refractory Follicular Lymphoma.

Before I get into the specifics of the trial, I want to explain why I think the situation is so interesting.

It's partly because I had no idea this was coming. I'm not an expert, as I have said many times before. I'm not an oncologist or a cancer biology researcher. I'm a Cancer Nerd, someone who was diagnosed with FL in 2008, and who reads and writes a whole lot about FL. I'm not an expert, but I consider myself pretty well informed when it comes to Follicular Lymphoma.

And yet, when I saw this headline on Fierce Pharma, I had no idea what Tafasitamab was, or that it was close to finishing a phase 3 trial.

The other reason it's so interesting is that I immediately searched this blog to see if I had written about it before and had just forgotten about it. And I found one post from the past that I had written. This how that post, written April 22, 2021, started out:

I like surprises.And I have to admit, this one surprised me. As much as I follow what's happening in the world of Follicular Lymphoma, I think this is the first I've heard of Tafasitamab. I searched the blog, and couldn't find any mention of it anywhere. But a phase 3 trial is just starting, looking at Tafasitamab combined with Lenalidomide (Revlimid)  and Rituxan (the two treatments that make up R-Squared). The trial involves patients with Relapsed and Refractory Follicular Lymphoma (they've already had at least one treatment that didn't work or stopped working).

 I laughed out loud when I read that. Apparently, I have heard about this treatment twice -- once at the start of the phase 3 clinical trial, and now at the end of the trial. 

This probably says more about the treatment and its maker than it does about me. Tafasitamab is also known as Monjuvi, and it was approved for use on DLBCL by the FDA in 2020 and by the EU in 2021. So it had already gone through all of the really heavy marketing and advertising that would have put it in the news. By the time I read about it, and especially since it was in a trial as part of a combination, it wasn't so "in your face" as it probably was its first time around.

So on to that "triumph" of a trial.

Tafasitamab is a monoclonal antibody, like Rituxan. But it's different in a couple of ways. First, it is "humanized," meaning it was developed from human cells, not mouse cells, like Rituxan. That has the potential to make it more effective and safer )fewer allergic reactions). The second difference is that is targets CD19, a protein on the FL cell. Rituxan targets CD20. So you have two different ways for an antibody to get to the cell. 

Tafasitamab has already been approved in combination with Revlemid (also known as Lenolidamide) for DLBCL. So you had the potential for a really great combination -- everything works together, compliments each other, and should have few new serious side effects,

And that's pretty much what the Tafasitamab + Rituxan + Revlimid combination does. The trial involved 548 patients with r/r FL. Half were given R-squared, and the other half had R-squared plus the Tafasitamab. 

The results were great. The patients in the TRR group had a median Progression Free Survival (their disease did not get worse) of 22.4 months, versus 13.9 months in the RR group. And that increased PFS was true no matter what group they looked at  -- POD24 patients, those who had received Rituxan, rhose who had recieved multiple treatments. The Complete Response Rate for the TRR group was 49.4%, versus 39.8% for the RR group. The Overall Response Rate was 83.5% versus 72.4%. 

As for safety, the results were similar for both groups. 99% of patients had some side effects in both groups (not a surprise). Grade 3 or 4 side effects happened in 71% of patients in the TRR group versus 69.5% of RR, and serious side effects were 36% versus 32%. During the study, 15 patients in the TRR group died, 5 because of disease progression and 6 because of side effects, versus 23 in the RR group (17 due to disease progression and 6 from side effects). Those death statistics are a good reminder that no treatment is without side effects, often very serious side effects.

But the bigger picture is this: adding Tafasitamab to R-Squared makes a very good treatment even more effective, and without a great increase in safety issues. 

I'm guessing this is going to be the Big Story about Follicular Lymphoma when the ASH conference is over, and we'll be hearing more excitement about it from the experts who give their opinions about things. The conclusion to the presentation abstract says this combination "represents a potential new standard of care option for patients with R/R FL." In other words, this will be the one everyone defaults to. That's a big claim. We'll see how the FDA process goes. But it will be really interesting to see what the experts have to say. Those are some very good numbers.

More to come, about this treatment and others.



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