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A summary of: Rheumatic Musculoskeletal Diseases as comorbidity in cancer patients (EULAR 2018 session)

13 June 2018 Leave a comment

EULAR2018_Logo

By  Professor Maria Suarez-Almazor (USA)

EULAR 2018 – Amsterdam, Wednesday, June 13th.

Immunoediting (ability of cancer to change its genes), a short introduction scope

Cells may develop from normal cells to tumor cells and the immune system tries to eliminate those tumor cells by acting on tumorcells antigens.

There can then be a phase of equilibrium with normal cells and (almost all of the) developing tumor cells that are continuously being eliminated by the immune system.

However at a given point a subfraction of the developed tumor cells can get into a so-called dormancy state*, i.e. their antigens are no longer recognised by the immune system

*Wikipedia; Dormancy is a stage in cancer progression where the cells cease dividing but survive in a quiescent state while waiting for appropriate environmental conditions to begin proliferation again.Quiescence is the state where cells are not dividing but at arrest in the cell cycle in G0-G1. Dormant cancer cells are thought to be present in early tumor progression, in micrometastases, or left behind in minimal residual disease (MRD) after what was thought to be a successful treatment of the primary tumor

Once the cancer is there management of the patient that also has a rheumatic musculoskeletal disease involves balancing between sustained low disease activity of the RMD as well as enhance cancer survival by at the same time keeping anti-tumor treatment effective.

Nice formulated in this tweet by

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The management of #RMD in cancer patients includes controlling the RMD (QoL) + maximizing tumor response (survival) #EULAR2018

There are no guidelines for the treatment of patients with e.g. rheumatoid arthritis and cancer, which is anyway very context dependent in clinical practice and demands a personal approach whilst keeping quality of life in mind.

One of the issues is what to do with biologics treatment in a rheumatoid arthritis patient with a malignancy.  And what about cancer recurrence and when may it be considered safe to resume biologics treatment after the patient has had cancer?

Generally spoken one should distinguish several settings e.g. cancer survivors, patients with chronic (more or less stable) cancer and end-of-life (terminal) cancer patients with a palliative treatment. For cancer survivors there seems (in general) no increased risk to resume (or initiate) biologics treatment for rheumatoid arthritis, especially when five years have passed according to expert opinion. There is no consensus on resuming biologics treatment earlier in these cancer survivor patients with RMD. For the chronic cancer patient with RMD however there is no recommendation at all. It all comes down to a personal and context-dependent approach.

Cancer immunotherapy (checkpoint inhibitors)

e.g. ipimilumab for the treatment of melanoma can have a delayed response in RMD patients. The ipimilumab actually acts in the opossite way as abatacept does. Whereas tumor cells suppress the immunological response (less T-cell interaction with the tumor cells), by enhancing (rather then inhibting like abatacept does) co-stimulation of T-cells the immune response is aggravated. Ipimilumab acts as an anti-CTLA-4 drug. Abatacept as a CTLA-4 agonist.

 

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this tweet was commented on by:

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(…) Kumar and Ballas describe an interesting case of a patient with preexisting myasthenia gravis that acutely worsened after receiving PD-1 blockade. This patient’s myasthenia gravis was unresponsive to multiple immunosuppressant drugs until he received abatacept, a CTLA-4 agonist, which profoundly improved his symptoms. The Food and Drug Administration has approved abatacept for use in patients with rheumatoid arthritis, and we agree that this is an example of how therapies developed for autoimmune disease may be applied in the treatment of immune-related adverse events and how multidisciplinary management can further improve outcomes. Since CTLA-4 blockade has been shown to be beneficial among patients with cancer, it would be important to ensure that abatacept does not have detrimental effects on antitumor immunity if additional patients who have adverse events associated with immune checkpoint blockade are treated with this agent.

[Correspondence Adverse Events Associated with Immune Checkpoint Blockade March 22, 2018 N Engl J Med 2018; 378:1163-1165 DOI: 10.1056/NEJMc1801663 Metrics]

Immunotherapy Related adverse events (irAEs)

Can be mild to life threatening!

The clinical pictures rheumatologist encounter when patients on immunotherapy are referred by the oncologists include:

  1. artritis/arthralgia (an oligoartritis type, an reactive arthritis like type and a rheumatoid arthritis type, the latter possibly already subclinical present before and becoming climical upon immunotherapy (checkpoint inhibitor)
  2. a polymyalgia rheumatica like syndrome which responds to corticosteroids but tends to re-occur upon resuming immunotherapy
  3. a polymyositis like clinical entity without rash and often lacking the accompanying antibodies, cave myocarditis

Management of immunotheraoy related adverse events (recommendations by ioncologists)

  1. early referral to rheumatologists
  2. discontinuation of immunotheraoy (temporary)
  3. immunosuppression starting with corticosteroids at higher dosages than normally would have been given in same rheumatic condition. Tocilizumab might be a promising option that does not seem to affect the immunotherapy efficacy too much, but this is from personal experience of Prof Suarez-Almazor and expert opinion, needs further investigations.

My summary from my handwritten notes having listened to this lecture that gives a scope and a general overview of several relevant aspects. It could well be incomplete and at points not fully correct, feel free to add comments or correct if necessary.

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Categories: meeting report

PARA study Rotterdam: >10 years of research on RA and pregnancy

26 September 2015 Leave a comment

The annual 2-day conference of the Dutch Rheumatology Association (NVR) took place last week. One of the invited speakers was Dr RJEM Dolhain (photo) from Erasmus University Medical Center, Rotterdam, the Netherlands. Dr Dolhain provided the audience with a nice overview of what over a decade of research (in the so-called PARA study 2002-2015) in rheumatoid arthritis and pregnancy has yielded so far. The Rotterdam PARA study can be considered as the world’s largest (and ongoing) study of pregnancy related topics in rheumatoid arthritis (follow-up of n=300 of which 250 women have become pregnant). The highlights (i.e. from my own notes during his excellent talk) are listed in this blogpost. Read more…

What is new in Sjögren’s Syndrome (EULAR 2013)

16 June 2013 Leave a comment

Hendrika Bootsma (The Netherlands) at EULAR 2013 Madrid, June 14.

Diagnosis / classification criteria

2013-06-15 11.44.27Criteria must be clear, easy to apply and specific. “The previous AECG classification criteria for Sjögren’s syndrome had been criticized for including subjective tests (symptoms of oral and ocular dryness), physiologic measures that lack specificity, and objective tests that are not diagnostically equivalent. Therefore, the Sjögren’s International Collaborative Clinical Alliance Research Groups proposed an alternative criteria set composed of only objective measures (including lip biopsy). The level of agreement between the preliminary American College of Rheumatology (ACR) criteria and the AECG criteria was high when all objective tests were available to define the AECG criteria but low when subjective tests were allowed to replace the objective tests.” (Bootsma, H., Spijkervet, F. K. L., Kroese, F. G. M. and Vissink, A. (2013), Toward new classification criteria for Sjögren’s syndrome?. Arthritis & Rheumatism, 65: 21–23. doi: 10.1002/art.37701) 

My selection of ACR2012 Sjögren’s Syndrome Abstracts (2)

18 November 2012 Leave a comment

This year’s annual scientific meeting of the American College of Rheumatology (ACR) included 76 accepted abstracts on Sjögren’s Syndrome. In this blogpost I name a selection of them that may have clinical relevance for rheumatologists in daily practice together with a few more basic research oriented abstracts that I personally consider of interest. Read more…

My selection of ACR2012 Sjögren’s Syndrome Abstracts (1)

17 November 2012 Leave a comment

It is early November, and that is usually the time of the year for the annual meeting of the American College of Rheumatology (ACR). Indeed the ACR 2012 convention has just ended while adding this blogpost. It took place in Washington, D.C., from November 9-14. I did not physically attend it, but -and that’s new- I would almost say it has been the first scientific meeting I could almost attend virtually (live video- and aaudiostrems from the meeting would provide a strikethrough for the word “almost” in this sentence). Thousands of tweets from all kinds of authors attending the ACR 2012 convention passed in my Twitter timeline. Whilst on a previous occasion one could make a nice survey of topics discussed at the ACR or (european counterpart) EULAR meetings by downloading a transcript of all tweets with the meeting’s hashtag via Symplur, on this occasion one could speak of a twitter tsunami. The tweets containing the hashtag #ACR2012 were so numerous that the previously mentioned transcript downloads via Symplur no longer satisfied my objective to obtain a nice survey of the meeting (this might change when Symplur decides to add more query features then only filtering based on a specified time-interval, i.e. if one could filter all tweets containing the #ACR2012 hashtag including the word “gout” it could still deliver a nice transcript of what came by via Twitter on the topic gout). Read more…

Categories: meeting report

Meeting report (part 4b): evaluating muscle function in inflammatory myopathies

1 February 2012 Leave a comment

Advances in basic experimental as well as clinical research on pathophysiological mechanisms and treatment opportunities of various rheumatoid disease conditions have been complicated or frustrated by issues like how to define a disease (i.e. proper diagnosis) and how to define measurement of treatment response (i.e. which outcome measuers should be targeted and evaluated in trials). In this blog, after putting things in a broader context shortly, I will write what I learned about evaluating disease activity of inflammatory myopathies in daily clinical practise, and to be more precise evaluating muscle functioning. Two standardised examinations are available for that purpose: the MMT-8 and the FI-2. Read more…

Meeting report (part 4a): about the shifting classification of idiopathic inflammatory myopathies

28 January 2012 3 comments

What I also heard during my 2-day visit to the Karolinska Institute at Stockholm, Sweden, was a nice overview on the current status of both classification as well as (emerging) treatment options of idiopathic inflammatory myopathies. As a clinician, three take-home messages were what I took home from this oral presentation by professor Ingrid Lundberg MD PhD (photo), who can be regarded as one of the top-experts worldwide in this field of rheumatology.
The first two of three take-home messages are nothing new at all when I search the literature, but I must admit my knowledge of inflammatory myopathies was not as up-to-date as I thought, because they were both quite new for me. They were: (1) the so familiar classification into polymyositis, dermatomyositis and inclusion body myositis is becoming rather obsolete and may be rapidly replaced by a calssification that is much more defined by which (combination of) myositis specific autoantibodies (MSAs), which I will discuss in this blog post. Read more…