Monday, 20 April 2015

AAN 2015: alemtuzumab retreatment rates low

Alemtuzumab extension data in injectable switchers continues to look very promising. #AAN2015 #MSBlog #MSResearch 

"The following data from the CARE-MS II extension study is being presented later this week at the AAN. It shows you that the effect of alemtuzumab is durable in that only one-third of MSers needed a third cycle of treatment after 4 years of follow-up. This means that in two-thirds of treated MSers two cycles of treatment were sufficient and they hadn't needed any DMT for 3 years. This number is likely to drop-off slightly with time. In the long-term follow-up of the open-label cohort from Cambridge 50% need a third course by year 7. In the latter study many MSers have now gone past 10 years without needing any other treatment with their disease in long-term remission. I have personal experience as a few of these are my patients and they are doing remarkably well considering that they all had very active MS, with a poor prognostic profile, prior to alemtuzumab treatment. The real question on everyone's lips is are these MSers cured of their disease? When will be confident enough to claim victory? Most in the field don't like using the C-word (C = cure) as it raises false expectations. My argument is if we don't define and look for a cure we will never find it. In addition, the only reason why some MSers want alemtuzumab, or induction therapies in general, is because of the potential for a cure. Why would you take the risks if not for a cure? This is almost certainly what is driving the current interest in HSCT (hematopoietic stem cell transplantation) as a treatment for MS. The is despite HSCT having a risk:benefit profile, that at least in the short-term, looks inferior to alemtuzumab. Put bluntly, MSers want the option of having HSCT. Are you surprised?"

"I bet some of you are interested in knowing what happens to brain atrophy in these MSers treated with alemtuzumab that are in long term remission. It is one thing being NEDA (no evident disease activity), but are they NEDA-4 ('normalised' brain volume loss). Does alemtuzumab treatment prevent end-organ damage? To be able to claim a cure MSers need to be deeply phenotyped to make sure all evidence of MS is gone. Phenotyped is a medical term for defining the diseased state. Normalising brain volume loss is one of the features on my list that needs to be ticked off if anyone is going to make the claim that their MS is gone."


"Some of you, who are new to this blog, may be interested in reading my previous post on defining a cure in MS."

Traboulsee et al. Durable Effect of Alemtuzumab on MRI Outcomes in Patients With Relapsing-Remitting Multiple Sclerosis Who Relapsed on Prior Therapy: 4-Year Follow-up of CARE-MS IINeurology, AAN 2015: P7.249. 

OBJECTIVE: Examine the effect of alemtuzumab on 4-year magnetic resonance imaging (MRI) outcomes in CARE-MS II patients who entered an ongoing extension. 

BACKGROUND: In the CARE-MS II trial (NCT00548405), alemtuzumab had superior benefit versus subcutaneous interferon beta-1a, including improved MRI outcomes over 2 years, in relapsing-remitting multiple sclerosis (RRMS) patients who relapsed on prior therapy. 

DESIGN/METHODS: Core study patients randomized to alemtuzumab received 12 mg/day intravenously on 5 consecutive days and on 3 consecutive days 12 months later. In the extension study (NCT00930553), alemtuzumab-treated patients could receive as-needed retreatment >1 year after the previous course. MRI scans were acquired at baseline and yearly thereafter. MRI outcomes included gadolinium (Gd)-enhancing, new/enlarging T2 hyperintense and new T1 hypointense lesion activity, and MRI activity (absence of Gd-enhancing and new/enlarging T2 lesions). 

RESULTS: 393 (92.9%) CARE-MS II alemtuzumab-treated patients entered the extension; data are available through 4 years from first treatment, and follow-up is ongoing. Through 4 years, 67.7% of patients received only the initial 2 courses of treatment, 24.2% received 1 additional course, and 7.4% received 2 additional courses. In Year 3 and Year 4, the proportions of patients free of Gd-enhancing (86.5% and 89.1%), new/enlarging T2 (69.0% and 70.3%) or new T1 lesions (87.5% and 86.3%) remained stable. Most patients were MRI activity-free at Year 3 (68.4%) and Year 4 (69.9%). 

CONCLUSIONS: The majority of alemtuzumab patients remained free of new lesions and MRI activity in Year 4 despite 68% of the patients receiving their last treatment course 3 years previously. These findings support the durable efficacy of alemtuzumab in this RRMS population. 

Study Supported by: Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals

CoI: multiple

10 comments:

  1. Will alemtuzumab work for rapidly orogressive Ms? As proposed by DrK

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    1. If your scan has gadolinium enhancing lesions ithink the answer is yes.

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  2. On the subject of how to define a cure for MS, there's a brilliant paper from Burman at Uppsala university hospital in Sweden (involved in Dr Burt's MIST trial). Have a butchers...!
    http://www.diva-portal.org/smash/get/diva2:714003/FULLTEXT01.pdf

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  3. Prof G,

    I hope I'm wrong, but this looks like results have been rebaselined? Only in this way can you get results stating 68.4% were MRI activity free at year 3 & 69.9% at year 4.

    The reason I find this misleading is because such statistics are not representative of the total number of particicipants who entered the study. So a participant may have shown MRI activity at year 3... retreated with Alemtuzumab... and then been MRI activity free at year 4. So they can be in the 69.9% MRI activity free statistic at year 4. But so what if they had MRI progression at year 3, which may or may not have resulted in disastrous consequences?! So their MRI was stable a year after a retreatment & compared to the 'new' rebaselined MRI that showed progression from year 1.

    What we need to see is the statistic reflecting MRI activity free patients since the START of the study. I think a more accurate analysis uses the disease-free statistic of 39% at 2 years (CARE-MS1).

    Could you please elaborate?

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  4. Prof G,

    I'm almost 10 years post Alem and completely stable - no sign of disease activity. As a doctor, surely you should be pushing such treatments for the sake of you patients' long term health. The first line injectibles can't get near this Alem's efficacy. Patient choice is one thing, but doctors should be giving a strong push where the evidence supports this ie the evidence of long term Alem efficacy.

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  5. Dear mice, Thank you for posting this. As I type Im waiting to start my infusion. I'm not expecting a cure but I do believe thanks to the phenomenal dedication and work from you and your team I will see it I my lifetime. What I do have is hope, something that Ms can take away. I know my Ms journey will be far less challenging thanks to this treatment than generations before me. And for that I am very grateful. Dairylee slices eroute to barts!

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  6. Is it not a little misleading to post results based on MRI activity free survival? Surely the stat we're interested in is Event Free Survival (ie no MRI activity, no relapse and no progression) before we start talking about a cure...?

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  7. Agreed with Matt. And isn't rebaselining a little misleading, as people are failing & requiring retreatments to rejoin the success group? Rebaselining seems to be disregarding the past, setting a new starting point (even though lesions & disability have been accrued by some since the original baseline). Prof G please explain how rebaselining benefits anyone other than the pharmaceutical company by making the results look better than they are.

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  8. I'm worried about the other C word-have any patients developed neoplasms after taking this med? Is that side effect carried over from more aggressive treatment as Campath for blood cancer?

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    1. My son was told there was an increased risk of lymphoma and to check his skin regularly re moles etc. but you are getting alemtuzumab at a far smaller dose than those who need it for CLL. You decide yourself on the risk: benefit ratio. If you can live with the small risk of developing cancer for the benefits of your MS stabilising then you'll go for it; if you can't, then don't. There isn't a cast iron guarantee- we all take risks, being overweight, not exercising enough, smoking, drinking- you just need to make an informed decision about what risks you are prepared to take.

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