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

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:
- Gary, an 18-year myeloma survivor, asks others in the forum what can be done to help the caregivers who give so much to support multiple myeloma patients
- Debbie keeps on going just like that famous battery bunny; she has provided an update about Days 9 and 10 of her autologous (own) stem cell transplant
- Lynda gives a lengthy introduction to how her husband, who is 72, was just diagnosed with multiple myeloma. He will be treated with Velcade, cyclophosphamide (Cytoxan), and dexamethasone
- KarenaD will soon have her autologous stem cell transplant. She is wondering when people usually have their stem cells reinfused during the transplant process.
New myeloma-related research articles
- Qaqish, I. et al., “Carfilzomib: a cause of drug associated thrombotic microangiopathy” in Transfusion and Apheresis Science, March 15, 2016 (abstract)
- 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)
- 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)
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.
Related Articles:
- FDA Approves Once-Weekly Dosing And Revised Safety Information For Kyprolis
- Common Measures Of Heart And Blood Vessel Health May Predict Risk Of Heart-Related Side Effects During Treatment With Kyprolis
- Eyelid-Related Complications Of Velcade Therapy: New Insights And Recommendations
- Once-Weekly High-Dose Kyprolis Yields Deeper Responses And Longer Remissions Than Twice-Weekly Kyprolis (ASCO & EHA 2018)
- ASCO 2018 Update – Expert Perspectives On The Key Multiple Myeloma-Related Oral Presentations
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.
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.
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
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.
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!
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!
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
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.