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

1. 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)
2. Arvatz, G. et al., “Heparanase and cancer progression: new directions, new promises” in Human Vaccines & Immunotherapeutics, April 6, 2016 (abstract)
3. 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)
4. 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)
5. 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)
6. Muthukrishnan, A. et al., “Medication-related osteonecrosis of the jaw: a dentist's nightmare” in BMJ Case Reports, April 6, 2016 (abstract)
7. Palladini, G. et al., “What is new in diagnosis and management of light chain amyloidosis?” in Blood, April 6, 2016 (abstract)
8. Zhu, W. et al., “11C-Acetate PET/CT monitoring therapy of multiple myeloma” in Clinical Nuclear Medicine, April 6, 2016 (abstract)