Good morning, myeloma world.

There are times when we write an edition of Myeloma Morning, and it turns out completely different than expected. Today's edition is a perfect example.

As we were planning today's report, we thought it would focus on two preclinical research studies examining the potential new myeloma therapies CCF642 and BDA-366.

And, yes, we do start today's report with summaries of those two studies.

But readers will be making a mistake if they stop after reading that section of today's article. Because the third study we discuss today is really interesting. It describes how human platelets can be used for tumor imaging and to deliver anti-cancer drugs directly to tumor cells.

And readers should keep going after the platelet study, because we wrap up today's report with an interesting study out of Korea that looks at potential links between M-spike and free light chain levels at diagnosis and heart-related problems.

CCF642 And BDA-366 Preclinical Research

We start the main section of our report today with a look at two studies that are similar to one another. Both report preclinical research results. So, before we dive into the details of the studies, we have to preface our comments with an important disclaimer. Many drugs show potential as myeloma therapies when they are tested in the laboratory. Only a limited number of drugs, however, actually prove that they have anti-myeloma activity – and an acceptable side effect profile – when they are actually used in myeloma patients.

So, with that caveat aside, the first study is by researchers based primarily at the Cleveland Clinic. They report on laboratory research investigating a potential new myeloma therapy known as CCF642 (abstract, full-text PDF). The drug belongs to a new class of possible drug therapies known as protein disulfide isomerase (PDI) inhibitors.

In testing of CCF642 involving myeloma cell lines in test tubes as well as in mice, the drug proved to have noticeable anti-myeloma activity. The study authors characterize the activity as similar to what has been seen with Velcade (bortezomib) when it was tested in a laboratory environment.

Several of the authors have applied for a patent on CCF642, and they also report favorably on the method they used to identify the drug as a potential myeloma therapy. It is not clear, however, whether CCF642 will be developed further as a myeloma therapy, or whether, instead, variations of it will be pursued for further development.

The second study is by researchers based primarily at Emory University in Atlanta. They report results of laboratory research investigating the anti-myeloma activity of a drug known as BDA-366 (full text).

BDA-366 belongs to a new class of drugs known as BCL2-BH4 antagonists. These drugs are part of a broader class of therapies, known as BCL2 inhibitors, which have attracted interest as potential cancer therapies. Several drugs in the broader class of BCL2 inhibitors have been investigated as potential myeloma therapies, including venetoclax (ABT-199), ABT-737, and obatoclax (GX015-070).

The Emory researchers tested BDA-366 against myeloma cell lines in both test tubes and laboratory animals. They find that their data “demonstrate that BDA-366, as a novel BH4-based BCL2 inhibitor ... could offer an entirely new tool for multiple myeloma therapy." The drug “effectively induces robust apoptotic death of human multiple myeloma cells."

As was the case with the study of CCF642, the Emory researchers also do not state explicitly whether further development of BDA-366 will be pursued. They do appear interested, however, in pursuing that option, should it be feasible.

Putting Useful Payloads On Platelets

Readers will have to forgive the informal way we introduce the next study in today's research review. But, quite simply, the study is cool. Very cool.

The study is by three researchers based in China and at the University of California – Berkeley. What they have done is modify blood platelets in several ways so that the platelets are (a) attracted to multiple myeloma cells, and (b) easily detected with imaging equipment (full text).

The researchers infused the modified platelets into mice that have transplanted myeloma cells. They then were able to observe the flow of the platelets to the infused myeloma cells. Eventually, the modified platelets accumulated almost solely where the myeloma cells are.

The study is basically a proof-of-principle of what can be done with modified platelets. They can be used for imaging purposes, or – perhaps more importantly – to carry anti-cancer therapies directly to the targeted cells. “Repurposed platelets,” the researchers write, “represent a new class of living vehicle for in vivo imaging, and targeted-delivery of protein therapeutics or small molecule cytotoxins to tumors.”

The authors note that platelets have many advantages as carriers of imaging or therapeutic “payloads”, including the fact that they do not typically generate an immune response, they can easily access tumor microenvironments, and they are large enough to carry a variety of different payloads at once.

As we said … very cool.

Type of Multiple Myeloma At Diagnosis And Heart Function

We'll close today with a study which the authors say may be the first of its kind. In particular, Korean researchers report on a connection they have found between, on the one hand, monoclonal protein levels in newly diagnosed multiple myeloma patients, and, on the other hand, measures of heart function (abstract, full-text PDF).

The authors found that newly diagnosed multiple myeloma patient with high M-spikes tend to have larger left atria of the heart and higher pulmonary artery pressure – both of which are, as we understand it, symptoms of pulmonary hypertension.

In patients with newly diagnosed light chain multiple myeloma, high light chain levels also were found to have a link to heart-related symptoms. But the link was different.

In particular, the researchers found a link only in patients with lambda light chain multiple myeloma, not kappa. In addition, the link was between elevated lambda free light chain levels and left ventricular ejection fraction. The higher the lambda free light chain level, the lower the left ventricular ejection fraction. (Ejection fractions are a measure of heart strength; healthy, strong hearts have higher ejection fractions.)

There are questions one can raise about this study. It is, for example, a single-center retrospective study involving patients who were planning on having a stem cell transplant, and the heart-related measurements were done after some initial treatment of each patient's multiple myeloma. It also is not clear if all patients planning to have a transplant had their heart function checked.

Nevertheless, it's difficult to be overly critical of the study, since heart health is an important issue in myeloma patients – particularly as new therapies are enabling them to live longer, and as some of those therapies have potential heart-related side effects.

New Myeloma-Related Research Articles

1. Dai, L. et al., “Human platelets repurposed as vehicles for in vivo imaging of myeloma xenotransplants” in Oncotarget, March 31, 2016 (full text)
2. Deng, J. et al., “BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth” in Oncotarget, March 31, 2016 (full text)
3. Vatolin, S. et al., “Novel protein disulfide isomerase inhibitor with anti-cancer activity in multiple myeloma” in Cancer Research, April 6, 2016 (abstract, full-text PDF)
4. Yi, J. E. et al., “Association between left ventricular function and paraprotein type in patients with multiple myeloma” in The Korean Journal of Internal Medicine, April 6, 2016 (abstract; full-text PDF)