I'm getting into the ASH abstracts now (all 282 of the Follicular Lymphoma ones), and there's actually a lot to think about. I'm finding the usual mix that I have found in the last few years -- lots of deeper looks into what we already know, some newer treatments (lots of combinations of new and old treatments), but no real blockbusters that I can see on first glance.
This first preview post is one of those "deeper dives into what we already know." It's a long-term follow-up of a study that compares Watching and Waiting to Rituxan in asymptomatic FL patients. As someone who watched and waited for two full years, and the had just Rituxan as a treatment, I am very interested in this study.
As the title indicates, this study involved 463 FL patients in the UK, Australia, New Zealand, Turkey, and Poland. They were divided into three groups: one group watched and waited, another was given just Rituxan, and the third had Rituxan + Rituxan Maintenance.
This research has been reported on before (the first patients in it were enrolled in 2004, even before I was diagnosed). Its purpose was to compare how well the three different approaches worked on patients who were a lot like me (and probably some of you)-- no symptoms, not a lot of large nodes, and didn't necessarily need treatment right away. The early results of the study found that after about 4 years, 88% of those in the maintenance group had not had a new treatment, and a similar number for the Rituxan-only group (compared to only 46% of the watch-and-waiters). However, there was no difference in Overall Survival for all 3 groups (which is kind of typical for FL treatments, no matter which ones they are comparing).
The researchers also report that "Selected [Quality of Life] measures were shown to be superior for patients in the RM arm compared to W&W." This is only a summary of the research, so they don't get into any more detail, but I'm very curious to know what they measured for Q of L. I'm guessing they were emotional issues, maybe? Getting some kind of treatment eases the emotional burden of watching and waiting? (Though it's also interesting that they "selected" Q of L measures. Maintenance can also lower immunity, since B cells are being targeted for a long period of time. maybe that wasn't considered a Quality of Life issue?)
Anyway, this presentation at ASH is a long-term follow up of the same patients -- a median of 12.3 years.
Researchers found that 242 of the patients from the study had needed a new treatment over that time -- 133 in the WW group, 42 in the Rituxan group, and 67 in the maintenance group. The median time that it took for a second treatment was 2.7 years for the watch-and-waiters, 9.9 years for the Rituxan group, and longer than that for the maintenance group (they had not reached the median, meaning less than half had needed a second treatment). After 10 years, 28.8% of watch-and-waiters had not needed a second treatment, compared to 49.4% in the Rituxan group and 64.5% in the maintenance group.
The median was not reached for any of the three groups for a next treatment after that first one.
Some of the other results from the study:
The 4 year progression-free survival for both Rituxan groups was better than for the W and W group.
There was no significance difference for Overall Survival between the three groups.
There was no significant difference in the time to transformation between the three groups.
There was no significant difference in rates of developing a new cancer between the three groups.
It's all a very interesting bit of research, and confirms a lot of what was found out years before. that's what is so interesting to me. Looking at the numbers, there seems to be a lot of evidence to show that watching and waiting isn't worth it, and some kind of Rituxan (with or without maintenance) is a better choice. And yet, we still have lots of people who are watching and waiting.
I think "choice" is the key word here. As I said above, the whole idea of "Quality of Life" has me wanting to hear more. How are they measuring it? Which "selected" qualities did they focus on? (If anyone in the class wants to do a research project for extra credit, feel free to take it on. Find the original research and report back to me. And yes, I am a teacher.)
But thinking about Quality of Life brings up another issue for me -- the emotional benefits of watching-and-waiting. I occasionally have FL patients contact me about treatment choices that their doctor has suggested, asking my advice, especially about watching and waiting. After I remind them that I am not a doctor, I tell them why W and W was a good choice for me, and I remind them that it's not a permanent choice. In other words, you can decide to wait until there are physical symptoms that make treatment necessary (which is what happened to me). But you don't need to wait that long. You can decide after a couple of months that the emotional burden of living with an untreated cancer is just too much. Tell your doctor you changed your mind. Ask for Rituxan. Most patients I talk to don't do that. they manage to live with W and W until it's necessary.
And maybe that's why people keep watching and waiting, even if there is evidence that treating right away is a good (maybe better) choice, at least by some measures. Maybe they hold off out of fear of what kind of side effects will come with treatment.
But maybe, just maybe, it's an emotional test that we give ourselves. We want to prove that we can beat the cancer without needing to be treated right away.
I'll have to think about that some more.
I'll keep looking at ASH abstracts and writing more soon.
Thank you for this.
ReplyDeleteI was diagnosed with 'Follicular Lymphoma' 2 months ago & am in the Watch & Wait phase. Will show this study to my oncologist & possibly start maintenance therapy.
Honestly, I have no desire to undergo any therapy, so I was okay with Watch & Wait. But as it stands, I would get a greater benefit from starting retuximab & maintenance therapy sooner.
I was diagnosed with follicular lymphoma in August 2011, have been on watch and wait ever since and still asymptomatic . It does get much easier to deal with psychologically over time, as these days I rarely think about it between annual check ups.
ReplyDeletePersonally, I would be hesitant to start treatment until the Covid pandemic is more in the rear view mirror, if I did not need to and watch and wait was still an acceptable option, as most lymphoma treatments will suppress your immune system, reduce the efficacy of further vaccines and make you more vulnerable to serious covid disease. Especially now that Evusheld and other Covid treatments have been shown to be less affective in protecting immunocompromised patients against the latest Covid variants.
This particular area of research is especially interesting to me as I am 6m into Watch and Wait for NHFL. I feel that discussion of treatment options is often focused on overall survival and doesn't consider the symptoms that watch and waiters have to deal with outside of the GISSI or GELF criteria for treatment so I was very curious to know what QoL measures were assessed. I have looked at the Lancet 2014 paper for the original study https://www.thelancet.com/action/showPdf?pii=S1470-2045%2814%2970027-0
ReplyDeleteand I've tried to pull out the relevant sections below;
The primary QoL objective was to identify whether treatment with rituximab results in increased functional wellbeing and reduced anxiety and depression at month 7 compared with watchful waiting.
The questionnaires used were the Functional Assessment of Cancer Therapy–General (FACT-G), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale–Revised, and questions from the Illness Coping Style, Illness Impact Bank, and Mental Adjustment to Cancer Scale together with four additional questions relating to lymphoma (appendix). Most of these focus quite understandably on psychological impact but the FACT-G questionnaire does have 4 sub scales: physical wellbeing, social or family wellbeing, emotional wellbeing, and functional wellbeing, each scored 0–100, with higher scores suggesting better Q. These do include measures that include fatigue, pain and impact on work. You can download the questionnaire here https://www.facit.org/measure-english-downloads/fact-g-english-downloads
There was a significant improvement in the Mental Adjustment to Cancer scale score from baseline to month 7 in the maintenance rituximab group(p=0·0001) that did not occur in the watchful waiting group (p=0·19), and Illness Coping Style were much the same in the maintenance rituximab group (p=0·072) but deteriorated in the watchful waiting group (p=0·0063). Patients in the maintenance rituximab group were also significantly less worried about the need for treatment for more treatment than patients in the watchful waiting and group there were no other clinically significant differences between the two arms in all other QoL measures between baseline and month 7 ie no statistically significant improvement was seen in the FACT-G scores which included fatigue and impact on work etc. I think its relevant to note that baseline scores were generally high but equally important there was no significant deterioration in physical or functional wellbeing scores within the treatment arms.
I think having looked through all this, that it's so important to have informed conversations with our doctors about our individual treatment priorities and concerns. Watch and wait is still an appropriate choice for many but moving to treatment earlier does have potential benefits and may just be worth a more detailed initial discussion at diagnosis. I'm not quite clear why some of us aren't given that opportunity for discussion.
Having access to this site and all the information you have shared is an incredibly helpful resource to support those discussions though so thank you so much Lympho Bob for all the work you put into this blog. I am extremely grateful.
Is there actually a reason why maintenance therapy with rituximab is stopped after 2 years? What would be an argument against maintaining a maintenance therapy as long as the patient tolerates it and possibly keeps the tumor burden within limits?
ReplyDelete