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Myeloma Morning: Kyprolis And Thrombotic Microangiopathy, Roneparstat, And SPRY2

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Published: Mar 28, 2016 12:17 pm

Good morning, myeloma world.

We hope your week is getting off to a good start. We've got a couple of new research studies to discuss in today's edition of Myeloma Morning, as well as several highlights from the Beacon's discussion forum.

On the research front, we'll start today by mentioning an article by physicians at the Mayo Clinic's Arizona campus. They report on a com­pli­ca­tion, known as thrombotic microangiopathy (TMA), that occurred in two multiple myeloma patients they had treated with Kyprolis (car­filz­o­mib) (abstract).

TMA is a con­di­tion marked by the formation of blood clots in the small arteries and capillaries of the body. One specific type of TMA is thrombotic thrombocytopenic purpura (TTP). Former Myeloma Beacon columnist Pat Killingsworth developed TTP prior to his passing last month (see related Beacon news article). Pat was being treated with Kyprolis at the time.

The Mayo Clinic researchers attempted to address the TMA that developed in their patients by carrying out thera­peutic plasma exchange, also known as thera­peutic apheresis, which removes components of a patient's blood from their body. Plasma exchange, however, was not a beneficial treat­ment. The cases of TMA only resolved after dis­con­tinu­a­tion of the Kyprolis treat­ment.

Today's list of new research also includes a look at the potential mechanisms by which the drug roneparstat (SST0001) may be able to improve the treat­ment of multiple myeloma (full text). Roneparstat is an investi­ga­tional drug being developed by the Swiss com­pany Sigma Tau Research. A Phase 1 trial of the drug in myeloma patients is ongoing in Europe, and an initial report from the trial was presented at last year's American Society of Hematology annual meeting (abstract).

In the new study, whose authors include scientists employed by Sigma Tau, researchers discuss laboratory findings showing how the enzyme heparanase may encourage the growth and spread of cancer tumor cells, including myeloma cells. The researchers also report findings indicating that myeloma ther­a­pies such as Velcade (bor­tez­o­mib) and Kyprolis can encourage myeloma cells to produce heparanase.

Roneparstat, on the other hand, is heparanase inhibitor. It limits the amount of heparanase that cells can absorb, both on its own, and when used in com­bi­na­tion with other myeloma ther­a­pies. The extent to which this effect has a significant impact on myeloma cells, however, will need to be determined through addi­tional clinical testing of the drug in myeloma patients.

The final new research article we want to mention is a report by researchers in China. They have in­vesti­gated a protein known as SPRY2 (also called “sprouty2”), which the human body naturally produces. The Chinese researchers carried out laboratory experiments to assess whether SPRY2 has any influence on multiple myeloma cells. They found that SPRY2 can inhibit the growth and survival of multiple myeloma cells. This means new drugs that stimulate the pro­duc­tion of SPRY2, or act in ways similar to SPRY2, could be used as new treat­ments for multiple myeloma (abstract).

(The research into the impact of SPRY2 on myeloma cells is influenced by earlier research into the impact of an area of the human genome known as microRNA 21, or miR-21, on myeloma cells and how resilient they are. If you are interested in the subject, this paper in­ves­ti­gates the potential connection between miR-21 and SPRY2.)

The trend con­tinues here at Myeloma Morning in terms of there being no new business-related news to report. The trend also con­tinues, however, in terms of there being quite a bit of recent activity in the Beacon discussion forum. Here are a few of the ongoing forum discussions we thought worth highlighting:

New myeloma-related research articles

  1. Qaqish, I. et al., “Carfilzomib: a cause of drug associated thrombotic microangiopathy” in Transfusion and Apheresis Science, March 15, 2016 (abstract)
  2. Ramani, V. C. et al., “Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype” in Matrix Biology, March 22, 2016 (full text)
  3. Yao, Y. et al., “Sprouty2 regulates proliferation and survival of multiple myeloma via inhibiting the activation of ERK1/2 pathway in vitro and in vivo” in Experimental Biology, March 22, 2016 (abstract)
About Myeloma Morning

Myeloma Morning is a com­pre­hen­sive daily review of multiple myeloma research and news.

Each edition of Myeloma Morning is compiled by The Beacon after a thorough search of publication databases and mainstream news sources. This search leads to the list of new myeloma-related research articles included at the bottom of every Myeloma Morning.

The top part of Myeloma Morning highlights and summarizes selected articles from the day's list of new publications. It also discusses any myeloma-related business or regulatory devel­op­ments that have occurred.

This two-part structure to Myeloma Morning makes it a perfect way to stay current on all myeloma-related research and news.

If you are a researcher, you can help The Beacon inform the multiple myeloma community of your work. When you and your colleagues publish a new study, feel free to email a copy of it to us shortly before (or shortly after) it is published. If you wish, include with your email any back­ground or explanatory in­­for­ma­tion you believe may help us if we decide to summarize your article for our readers. Our email address is , and we respect embargo requests.

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8 Comments »

  • Nancy Shamanna said:

    Thanks for the Myeloma Morning update. The information about TTP, which Pat K. developed, is informative. I still think of Pat and all of the helpful suggestions he made over the years. He is missed. The TTP diagnosis was tragic, I know.

  • christina said:

    So, I wonder, if you're on Kyprolis, as Pat was, is there any way to know that this is happening BEFORE it is fatal? Are there warning signs? Kinda worried about this.

    Thanks for the informative article.

  • Rhonda said:

    I agree with Christina about the worry, as I am currently being treated with Kyprolis as a maintenance therapy. I am not refractory nor have I relapsed. Should I ask my treating physician about this?

    Thanks

  • Boris Simkovich (author) said:

    Thanks for your comments and questions everyone.

    We will check with the study authors to see what sort of signs there might be that this Kyprolis-related complication is developing.

    Keep in mind that the article we described is about the complication developing in TWO patients. The article is not suggesting that this is a common Kyprolis side effect. Instead, the authors just want to make sure physicians are aware of the potential complication.

    With that in mind, it would be fine if you mentioned the article to your doctor, Rhonda. He or she already may be aware of the study. But, if you bring it up, you can make sure there's awareness of the study, and, at the same time, you will get across that you are being proactive in staying educated about your disease.

  • Rhonda said:

    Thank you so much for the quick reply. I have forwarded this article to my local oncologist and will discuss this with him on my next visit. I look forward to hearing of any possible signs there might be. If he feels it is warranted, I will discuss with my multiple myeloma specialist. By the way, thank you for Myeloma Morning – it is very interesting. This site is amazing!

  • Allison said:

    I'm starting my fifth month of Kyprolis / dex treatment. Two patients out of many doesn't worry me. I have enough to worry about!

  • JPC said:

    To Boris and Team:

    I wanted to let you know that this is quickly becoming my favorite feature on the Beacon. Thank you very much. Regards

  • Boris Simkovich (author) said:

    Christina and Rhonda - We published more about TMA and Kyprolis in today's issue of Myeloma Morning.

    Allison - Yes, TMA is definitely a rare side effect, so it's not something to lose sleep over. We just want to be sure everyone knows what it is and how to recognize when it might be happening.

    JPC - Thanks for your feedback. We're glad you're enjoying Myeloma Morning.