Myeloma Morning: Kyprolis And Immunotherapy Targets, And A PET/CT Reminder

Good morning, myeloma world.
As we were finalizing today's edition of Myeloma Morning, we were suddenly reminded of how international the field of multiple myeloma research truly is.
The first research study we review below is by a team of German researchers. We also discuss two studies by Korean researchers, and a topic sparked by a report written by Chinese researchers. At the end of today's report, the list of new myeloma research articles also includes publications by investigators in India, Israel, Italy, and the United States.
As we said: International.
Speaking of the article by German researchers, it describes work they have done which could aid the development of immunotherapies that work particularly well with Kyprolis (carfilzomib).
We also spend some time in the report reminding ourselves – and our readers – that there can be more than just one “flavor” of PET/CT.
Finally, we look at two studies out of Korea. One is about thalidomide (Thalomid) maintenance therapy, and another is about severe infections in patients treated with Velcade (bortezomib).
We also will mention here that the list of new myeloma research at the end of this article includes a couple of case reports, a discussion of the role of heparanase in cancer (including multiple myeloma), and – for those who might be interested – an article from Blood about “what's new in the diagnosis and management of light chain amyloidosis.”
Developing Better Immunotherapies For Use With Kyprolis
The first study we'll look at today is an example of research designed to help find more effective future treatments for multiple myeloma.
The study is by investigators at the University of Tübingen in Germany. They report on their effort to identify targets for immunotherapies to be used in combination with Kyprolis to treat multiple myeloma (full text).
The motivation for Tübingen study is the impact Kyprolis and other drugs in the proteasome inhibitor class of therapies – which includes Velcade and Ninlaro (ixazomib) – have on myeloma cells.
In particular, it is known that proteasome inhibitors change which molecules are most frequently found on the surface of myeloma cells. This includes molecules, known as antigens, which are typically targeted by immunotherapies.
So, if the goal is to develop new immunotherapies that work really well with drugs like Kyprolis, then it is a good idea for the new immunotherapies to target the sort of molecules found on myeloma cells that are left after treatment with Kyprolis. If, instead, the new immunotherapies target molecules found on untreated myeloma cells, they may not add much to what Kyprolis already does when treating myeloma.
So the Tübingen researchers developed a laboratory-based methodology for measuring possible immunotherapy targets on multiple myeloma cells treated with Kyprolis. The details of their findings are beyond the scope of this report. However, we will say that the researchers were able to identify at least one important group of possible "Kyprolis-friendly" immunotherapy targets, and they believe their results “may have broad implications for the implementation of antigen-specific treatment approaches in patients undergoing [Kyprolis] treatment.”
Alternative Tracers For PET/CT In Multiple Myeloma
We turn next to discussion of a general topic rather than a specific study. We bring up the topic, however, because of a study in today's list of new myeloma-related research (see the end of this article). The "study" is a short paper by Chinese researchers, comparing different approaches to doing PET/CT imaging in a multiple myeloma patient.
This new paper reminded us that we, in turn, should remind our readers that there are different radioactive “tracers” that can be used to generate PET/CT images. The most common tracer used for PET/CT in multiple myeloma patients is “FDG” – or more specifically 18F-FDG (fluorodeoxyglucose with the fluorine-18 isotope).
However, there are other tracers that have been investigated for use in multiple myeloma patients, and some of them have shown results arguably superior to FDG.
A recent review of imaging techniques for multiple myeloma, for example, notes that the tracers 11C-acetate, 11C-choline, 11C-methionine, and 18F-alpha-methyltyrosine have been investigated for potential use in multiple myeloma patients – often with promising results. The Chinese study mentioned above compares the use of 11C-acetate and 18F-FDG in a single patient.
The review also notes, however, that “these new tracers are not widely available yet, usually require an on-site cyclotron for isotope production, and an on-site radiochemistry for tracer synthesis.”
Just remember: PET/CT doesn't always have to mean 18F-FDG PET/CT, and we may be hearing more about alternative tracers in the future.
Thalidomide For Post-Transplant Maintenance Therapy
We wrap up this edition of Myeloma Morning with two studies by separate groups of researchers based in Korea.
The first study is a retrospective investigation of the impact of thalidomide maintenance therapy in transplant-eligible multiple myeloma patients (abstract).
We mention this study mainly to alert those who are particularly interested in the issue of maintenance therapy. The broad significance of the study is somewhat limited given that it is a retrospective study, and given its focus on thalidomide as the maintenance agent.
That said, the findings of the Korean maintenance study will sound familiar. The researchers find that maintenance led to an improvement in progression-free survival, but there was only a trend to improved overall survival.
Severe Bacterial Infections During Velcade Treatment
The second Korean study is not an entirely new study; it was published in February. However, the study just recently came to our attention, it's about a subject of potential interest to our readers, and the full text of the study is available online at no charge. So we thought we would discuss it briefly.
The study investigates which factors may affect a myeloma patient's risk of contracting a severe bacterial infection while being treated with Velcade. The researchers identified three key factors: poor general health (“performance status”), being in the first or second cycle of treatment, and having a low lymphocyte level at the beginning of the treatment cycle.
The probability of developing a severe bacterial infection was highest in patients with all three risk factors (60 percent) and decreased with the number of risk factors (24 percent with two risk factors, 15 percent with one risk factor, 5 percent in the absence of risk factors).
The researchers recommend that patients with the risk factors they identify be more closely monitored for the development of severe bacterial infections during Velcade-based treatment. However, they do not recommend preventive use of antibiotics to reduce infection risk, as they believe evidence about that anti-infection strategy is still inconclusive.
(Note that the authors of this study use the term “treatment course” for what many other authors usually describe as “treatment cycle”.)
New Myeloma-Related Research Articles
- Allegra, A. et al., “Extramedullary plasmacytoma of the maxilla simulating a maxillary radicular cyst: quick diagnosis and management” in the Journal of Craniofacial Surgery, April 5, 2016 (abstract)
- Arvatz, G. et al., “Heparanase and cancer progression: new directions, new promises” in Human Vaccines & Immunotherapeutics, April 6, 2016 (abstract)
- Hyun, S. J. et al., “Pretreatment lymphopenia, poor performance status, and early courses of therapy are risk factors for severe bacterial infection in patients with multiple myeloma during treatment with bortezomib-based regimens” in The Journal of Korean Medical Science, February 22, 2016 (full text)
- Kowaleski, D. J. et al., “Carfilzomib alters the HLA-presented peptidome of myeloma cells and impairs presentation of peptides with aromatic C-termini” in Blood Cancer Journal, April 8, 2016 (abstract)
- Lee, H. S. et al., “The clinical impact of thalidomide maintenance after autologous stem cell transplantation in patients with newly diagnosed multiple myeloma in real clinical practice of Korea” in Annals of Hematology, April 6, 2016 (abstract)
- Muthukrishnan, A. et al., “Medication-related osteonecrosis of the jaw: a dentist's nightmare” in BMJ Case Reports, April 6, 2016 (abstract)
- Palladini, G. et al., “What is new in diagnosis and management of light chain amyloidosis?” in Blood, April 6, 2016 (abstract)
- Zhu, W. et al., “11C-Acetate PET/CT monitoring therapy of multiple myeloma” in Clinical Nuclear Medicine, April 6, 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:
- 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
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Once-Weekly High-Dose Kyprolis Yields Deeper Responses And Longer Remissions Than Twice-Weekly Kyprolis (ASCO & EHA 2018)
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma