Rituximab hailed as a breakthrough for millions with Chronic Fatigue

[AussieNeil]

A couple of days ago Sue (wroxham) mentioned yuppie flu in response to Ducksoup's post 'Fatigue, frustration and Community':healthunlocked.com/cllsuppo...

So I was very interested to read two New Scientist articles from early this month, commencing with:

Chronic fatigue breakthrough offers hope for millions

newscientist.com/article/mg...

So what is the breakthrough? This related article in New Scientist explains that it is Rituximab/Mabthera, the monoclonal antibody that is used with many CLL treatments to provide deeper and longer remissions and for some of us, the possibility of a cure with FCR:

Antibody wipeout relieves symptoms of chronic fatigue syndrome

newscientist.com/article/mg...

"The latest study implicates the immune system (in Chronic Fatigue Syndrome), at least in some cases. Rituximab wipes out most of the body's B-cells, which are the white blood cells that make antibodies.

Øystein Fluge and Olav Mella of the Haukeland University Hospital in Bergen noticed its effect on CFS symptoms in 2004, when they used the drug to treat lymphoma in a person who happened to also have CFS. Several months later, their CFS symptoms had disappeared. A small, one-year trial in people with CFS in 2011 found that two-thirds of those who received rituximab experienced relief, compared with none of the control group.

The most recent study, involving 29 people with CFS, shows that repeated rituximab infusions can keep symptoms at bay for years (PLoS One, DOI: 10.1371/journal.pone.0129898). "Eleven of the 18 responders were still in remission three years after beginning the treatment, and some have now had no symptoms for five years," says Fluge. "Suddenly, their limbs started to work again and their hands were no longer cold or sweaty."

(Both New Scientist articles can be read if your register (free); you don't need a New Scientist subscription.)

Is anyone that has struggled with the sometimes crippling fatigue that comes with CLL really surprised?

Neil

[jangreen]

Hi perhaps this may be a reason to start treatment for some people with chronic fatigue early with rituixiam and see what the results are. Perhaps researchers will now take the subject up. Best wishes

[wroxham-gb]

Great follow up Neil. Hopefully the 150 study group will show some same results. Hopeful.

Best wishes

Sue

[AussieNeil Partner Administrator in reply to wroxham-gb]

Considering CFS (or whatever you want to call it) has become a catch all term for people with chronic fatigue where doctors can't find any underlying reason for the fatigue, I'm actually surprised that as many as two thirds of those given Rituximab experienced relief. Those people must be feeling extremely grateful for that evidence that their fatigue is not psychological.

It certainly would be exciting news if researchers can find the underlying reason as to how B lymphocytes cause this fatigue and if further research confirmed that the same mechanism was behind the fatigue suffered by those with CLL. As Jangreen said, perhaps that could help identify a group of CLL patients that will benefit from Rituximab monotherapy maintenance treatment. 'Significant fatigue' is already one of the recognised triggers for treatment of CLL, but it seems you have to really be struggling before your specialist will actually initiate treatment on that criteria.

Neil

[Ducksoup]

Neil, this is fascinating. I think we should all stamp our little feet in unison until somebody does a larger test on those of us who suffer fatigue in even early stage CLL.

[Spiritlove in reply to Ducksoup]

Good to know I am not the only one tired out all day and evening, having to cancel seeing friends, going places and the heatwave has knocked me out. I had to spent all last Wed and Thursday lying on the bed, curtains closed and the fan full on. Fatigue must be part of CLL as so many of us have it. x

[MsLockYourPosts Passed Volunteer]

There was a discussion of this study on a Follicular Lymphoma page with Follicular patients who had Rituxan monotherapy not finding relief from their fatigue (a side effect or CFS, but the treatment was for the Follicular. Without a double blind study I think it would still be hard to determine how much is physical and how much is psychological as there is nothIng concrete to measure with CFS.

[AussieNeil Partner Administrator in reply to MsLockYourPosts]

You'd think that enough people with CLL have had Rituximab monotherapy for someone to notice any effect on fatigue, but it does seem that researchers don't take this common CLL symptom sufficiently seriously.

Obviously there needs to be more independent trials on CFS patients and ideally double blind to see if the New Scientist is becoming overly sensational with its headlines...

[HAIRBEAR_UK Founder Admin in reply to AussieNeil]

An interesting topic Neil, very thought provoking.

I think that rituximab as a single agent to treat CLL has been used contrary to CLL treatment and management guidelines mainly in the US? Not sure how all the information from these treatments there have been collected and aggregated? What does Dr Sharman say?

This is a quandary, how much of the day to day fatigue that CLL patients experience is down to CLL cells influencing this or other contributors. We know from surveys and research that when CLL is treated fatigue levels may eventually reduce is this down to specific agents or treatments or because the CLL is in remission?

The 2014 CLLSA survey, quantitative results showed that fatigue was the most frequently reported physical issue while on watch & wait with 72% of respondents reporting this issue. Post treatment this decreased to 47%, this was over many different treatment types but not many of the new experimental therapies and did include the effects during treatment itself.

CLLSA Quality of life Survey Results - October 2014

• Quality of life issues for People living with CLL - cllsupport.org.uk/cll-sll/l...

• Snapshot of the CLLSA quality of life Survey Results - cllsupport.org.uk/cll-sll/l...

• CLLSA QoL full data summary - link to PDF ukcllforum.org/downloads/20...

Is it surprising that a therapy that removes CLL cells or faulty signalling by these cells reduces fatigue, monoclonals work as effective therapies in treating autoimmune conditions many CLL treatments use different antibody therapies and modulators..

The quandary for me is that fatigue is not a sole reason to initiate a treatment but it may be considered appropriate by a clinician. Some research on interim therapies using antibody therapies would seem worth investigation. Is there existing data on the effect this has on long term CLL?

Does inappropriate 1st line use of a monoclonal as a single agent in CLL influence the evolution and future development of the disease? We know that the current message in CLL is that your first CLL treatment is your most important when considering your long term treatment plan.

There are several studies of monoclonals in use as maintenance therapy in CLL a current one now in for appraisal by regulators is using Ofatummumab it will be interesting to mine the data to see if there is any corresponding improvement in fatigue levels reported. Also there are trials starting up that will be using Obinutuzimab as a consolidation therapy.

We could do with some qualified input to this discussion from clinical researchers.

There is no doubt that involvement of patients and patient groups are required in trial design , management and delivery to ensure patint perspectives and important patient data in the area of QoL and ability to carry out tasks involved in daily living is captured and that areas around management of symptoms are considered by both independent investigator lead trials and industry trials. We can work to influence this by joining the appropriate patient engagement groups to represent and advocate for our community.

[AussieNeil Partner Administrator in reply to HAIRBEAR_UK]

Thanks Nick, for a good summary of the background into Rituximab monotherapy and the issues associated with seriously tackling CLL fatigue. I'd say that you are right about Rituximab monotherapy (which I agree is not an accepted standard treatment practice) being mainly practised in the US from what I've heard reported on CLL forums.

Dr Sharman said on this topic "I will admit that I have given this therapy a limited number of times in CLL/SLL before under circumstances where I thought it might be appropriate. In CLL/SLL I think rituximab monotherapy is mostly outdated as of late 2014."

cll-nhl.com/2014/11/rituxim...

So it seems we've missed the chance to collect any data to confirm or disprove the effectiveness of Rituximab monotherapy in reducing CLL related fatigue, particularly when you add in the valid reasons you mentioned about making your first treatment count. The results you've reported from the 2014 CLLSA survey illustrate how much treatment can improve our fatigue levels and anecdotally, I'm impressed by the number of times patients state how much better they are feeling energy wise within a week or so of starting on the new non-chemo CLL treatments. The big question that needs to be answered is whether we can safely undertake any treatment to reduce our tumour burden enough to improve our fatigue without worsening our long term prognosis and overall quality of life - and unfortunately that will take years to do.

It does indeed seem that our best chance of successfully tackling this common quality of life destroying issue is to lobby for some patient driven changes to trials to quantitatively evaluate the improvements in fatigue from different treatments. It's definitely not getting the degree of attention that it deserves. As Ducksoup says above, "we should all stamp our little feet in unison until somebody does a larger test on those of us who suffer fatigue in even early stage CLL."

Neil

[mehall51]

Neil;

Very interesting and I am hoping that having completed cycle 6 on FCR (26th July) my energy levels will gradually improve. While the CLL brought fatigue as part of its portfolio, it was nothing compared to the FCR sessions which proved totally draining. I look forward to a few months hence and flattening out a few dimples on some golf balls, and feeling good afterwards.

Onwards and upwards

Mike

[StupidPlanet]

I was about to start a Jakafi trial for CLL fatigue but was pulled due to prior renal cell carcinoma. They were concerned the nature of Jakafi could cause a relapse.

Now the docs are considering Rituximab as a single agent for my fatigue. They say most people feel great after.