Hot off the presses:
The Journal of Clinical Oncology just posted an abstract for "Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131 I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016."
The article reports on a 10 year follow up of a randomized trial. Half of the 531 patients were given R-CHOP, and half were given CHOP + RIT, or RadioImmunoTherapy, in this case 131I-Tositumomab, also known as Bexxar.
(If you need a reminder: RIT is kind of a super-charged Rituxan. Imagine a dose of Rituxan, which seeks out the CD20 protein on FL cells. But now add a drop of radiation to each bit of Rituxan, so those cells get the radiation delivered right to them.)
Over 10 years, the Progression-Free Survival was 49%, and the Overall Survival was 78%. The CHOP-RIT group had a better PFS than the R-CHOP group (56% vs 42%).
But there was no significant difference in Overall Survival between the two groups.
There was no difference in the incidence if secondary malignancies or myelodysplastic syndrome (sometimes called pre-leukemia) or acute myeloid leukemia (an aggressive type of leukemia). But there was a higher incidence of death from MDS and AML in the RIT group.
The researchers conclude that all of this points to Immunochemotherapy (R-CHOP in this case, but also R-Bendamustine and maybe CHOP or Benda + Obinutuzimab) remains the best choice for high-risk FL patients for a first treatment.
Two reasons for this:
First, there are the problems with RIT. Studies of RIT showed a great response -- about 70%. As this study shows, the response is not only broad, but durable -- patients can go a very long time without another treatment (the FL patient and advocate Betsy de Parry has gone over 15 years since her RIT treatment). But problems with payments and administration have made it underused (see the discussion of RIT at Lymphomation.org). It's so underused that Bexxar isn't even available anymore. It's a real shame.
And the other reason is the lack of difference in Overall Survival. If there is no difference in OS, there is no reason to go through the difficulties that come with administering RIT.
Two thoughts from me as I read this, for what they are worth:
1) It's pretty frustrating to read so many research reports that compare treatments, and have none of them show an Overall Survival benefit greater than the others. There has to be something out there that breaks through all of this. I don't know if it will be a single treatment or a combination, but I hope that something, at some point, breaks from the pack. Maybe it's already out there, in a clinical trial somewhere. It's a good reminder that we need to keep trials in mind when it comes to decisions about treatment -- there's no way to get new treatments without people to test them. (And since I have the Lymphomation.org page open, here's a link to their Clinical Trials page.)
2) It's also frustrating to see RIT be so successful, but see it so underused. I have a kind of emotional attachment to RIT. Another RIT, Zevalin, was approved a couple of years after I was diagnosed, and I remember being really excited about it. Over the next few years, I saw all the problems it was running into. Frustrating.
I talk a lot about "having more arrows in our quiver." That's the phrase that was used by the Lymphoma specialist that I saw a few days after I was diagnosed. He was talking about treatments available, and how each new treatment was another weapon available to us -- another arrow in the quiver. I've always thought that more arrows, more available treatments, was better for us. If the F;l comes back, there's something else to try.
I'm getting to the point where I don't want more -- I want better. I'd be pretty happy with fewer choices if those choices were personalized, and I knew they had a good shot at working for me, individually, based on the biomarkers that get found on my cells.
But that's a hope more than a reality, at least for now. I'll stay satisfied with my quiver full of arrows, trusting there's another one there when I need it.
In the meantime, I'll keep reading and reporting. And staying hopeful.
Interesting, and frustrating about the lack of difference in OS. Thanks for posting.
ReplyDeleteHi Bob, I think this subject of market acceptance for Radioimmunotherapy is a very interesting one.
ReplyDeleteI thought you maybe would be interesting in this smoking fresh podcast episode about Betalutin from Nordic Nanovector, which is a RIT based on Lu-177. It will definetly need to tackle just this subject in order to have any kind of success:
https://soundcloud.com/user-972208711/episode-36
I was a participant in the FOLE-BRITE trial at DHMC: R-B then RIT (Zevalin). I recognize that RIT involves extra concerns and it was administered very cautiously which may not be able to be accomodated outside of a large facility. However, PET scans which involve F-19 tagged glucose are administrated routinely by technicians, although doses may be lower.
ReplyDeleteRE: OS vs PFS. As a research analytical chemist, I am often dismayed by the selection of success parameters in trials. For a young otherwise healthy patient PFS seems to me to be more important than OS which is confounded by all sorts of uncontrolled variables, e.g., age, cardiovascular issues, lifestyles, etc.
The reason that different studies show no difference in OS after 5, 10, 15 years of follow up is following: 80% of FL patients have life expectancy comparable to general population - all of them are alive at the follow up time. Another 20% are PFS12 patients - they are simply not alive after 5 years irrespective to the treatment they used. Hence the OS after 5+ years of follow up is always the same. There are two conclusions can be made from this: 1)the real difference in OS for different treatment methods can be seen only after 20-25 years ; 2)the PFS12 patients must not waist time/money trying conventional treatments again and again - they must go straight to radical methods such as SCT or CAR-T. Then we will see that at least half of those 20% will get life expectance like the lucky 80%.
ReplyDeletePerfect explanation, Fanis.
ReplyDeleteThanks
Rodrigo
Brazil
Sorry, but I am not familiar with PFS12, does that mean patients who do not achieve progression-free survival after 12 months?
ReplyDeleteYes, patient that don't achieve 12 months PFS after Chemoimmunnotheraphy (normally R-CHOP)
ReplyDelete