Good morning, myeloma world.

We hope this Sunday edition of Myeloma Morning finds you rested and ready to do some quick myeloma-related catching up.

We always enjoy reporting on potential new myeloma ther­a­pies, so we thought we'd start today's update with a look at a new study by Korean researchers work­ing at LG Life Sciences. The researchers report results of preclinical (laboratory) tests they have carried out on two drugs, codenamed LC53-0110 and LC53-0151 (full text: html, pdf). Both of these drugs are in the same class of ther­a­pies – known as protea­some inhibitors – as Velcade (bor­tez­o­mib), Kyprolis (car­filz­o­mib), and Ninlaro (ixazomib). Like Ninlaro, LC53-0110 and LC53-0151 can be admin­istered orally; they do not need to be inected or infused, as with Velcade and Kyprolis.

The testing of LC53-0110 and LC53-0151 was done com­pletely in the laboratory; it did not involve any testing in myeloma patients. Still, the research was extensive, involving tests in multiple myeloma cell lines, in test tubes and in laboratory animals.

The authors were impressed with what they found in terms of the efficacy of LC53-0110 and LC53-0151 as potential anti-myeloma ther­a­pies. They stopped short, however, of recommending that one or the other of these two drugs be in­ves­ti­gated further in human testing. Instead, they recommend addi­tional laboratory testing of the drugs and other related com­­pounds to select a final can­di­date for clinical trials in patients.

The Korean research certainly con­firms that the investigation of addi­tional proteasome inhibitors as possible myeloma ther­a­pies is forging ahead. Just a few days ago, we reported here on research related to the proteasome inhibitor marizomib, and at least two other proteasome inhibitors – oprozomib from Amgen and VLX1570 from the Swedish com­pany Vivolux – are being in­ves­ti­gated as potential myeloma ther­a­pies.

Next, we turn to a study by researchers in Barcelona, Spain. As with a study we discussed yesterday, this new study looks at “asymptomatic multiple myeloma,” which includes mono­clonal gammopathy of undetermined significance (MGUS) and smol­der­ing multiple myeloma. As with the study discussed yesterday, the Spanish study in­ves­ti­gates factors that may signal whether someone with MGUS or smol­der­ing myeloma is likely to progress to symp­tomatic multiple myeloma – that is, myeloma requiring treat­ment (abstract, related ASH 2013 poster abstract).

In the Spanish study, the focus is on whether levels of a patient’s immuno­glob­u­lins may signal their likelihood of pro­gres­sion. The researchers use a technique that allows them to measure immuno­glob­u­lin levels based not just on whether the immuno­glob­u­lin is IgA, IgG, or IgM. Instead, the more precise test, which is sold commercially as the "Hevylite" assay, measures light-chain specific subtypes of IgA, IgG, and IgM – that is, IgA kappa, IgA lambda, IgG kappa, and so on.

The researchers used this mea­sure­ment technique on blood samples from 87 MGUS patients and 27 smol­der­ing myeloma patients diagnosed between 1983 and 2003 at the authors' treat­ment center. They found that the levels of the more specific immuno­glob­u­lin types affected pro­gres­sion in different ways depending on whether a asymptomatic patient was of type IgA, IgG, or IgM.

In IgA and IgG patients, pro­gres­sion was more likely if any IgM immuno­glob­u­lin (either IgM kappa or IgM lambda) was below the normal range.

In IgM and, once again, IgG patients, pro­gres­sion was more likely if any IgA immuno­glob­u­lin (either IgA kappa or IgA lambda) was below the normal range.

These results are similar in spirit to pre­vi­ously reported findings, such as those from the Mayo Clinic for MGUS patients (abstract, full text), regarding Hevylite testing and risk of pro­gres­sion.

We’ll wrap up our research review today with brief mentions of two addi­tional studies.

First, researchers at Stanford University have published a report with meta-analyses of studies investigating the possible connection between the herbicide Roundup (glyphosate) and several blood cancers  (full text: html, pdf). They find that existing studies do suggest a connection between Roundup exposure and an increased risk of developing multiple myeloma, but the connection is "marginally statistically sig­nif­i­cant."

Second, a group of French physicians report on a case of light chain deposition disease (LCDD) in the liver of a multiple myeloma patient (abstract, full text pdf). LCDD is similar to amyloidosis, in that it involves the formation of light chain deposits within the body. In LCDD, however, the deposits have a grain-like form, which is different from the form the deposits take in amyloidosis.  The liver-related LCDD in the French report developed after the patient had received her first cycle of Velcade and dexa­meth­a­sone. It was initially severe, but resolved with further Velcade-dexamethasone treat­ment.

Since it's the weekend, you probably won't be surprised to learn that we don't have any myeloma-related business news to report. It has been, however, a busy 24 hours in the Beacon's discussion forum since the last edition of Myeloma Morning, so we have a couple of ongoing conversations we thought we would highlight: 

• Forum member “faithoverfear” is interested in hearing if anyone who has been treated with Ninlaro (ixazomib) has experienced heart-related side effects
• CathyAnn reports on her first massotherapy experience since being diagnosed with smoldering myeloma in January
• Mort is 90 years old and has MGUS; he wonders whether his disease is likely to progress to symptomatic multiple myeloma given his age and general health
• Cheryl G reports on some (very positive) changes going on in the treatment of chronic myeloid leukemia and wonders if similar changes will occur in the treatment of multiple myeloma 

New myeloma-related research articles

1. Brilland, B. et al., “Recovery from LCDD-associated severe liver cholestasis: a case report and literature review” in the Journal of Gastrointestinal and Liver Diseases, March 2016 (abstract, full text pdf)
2. Chang, E. T. et al., “Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers” in the Journal of Environmental Science and Health, Part B, March 25, 2016 (full text: html, pdf)
3. Liu, M. et al., “Che-1 gene silencing by inhibiting mutant p53 expression” in Biochemical and Biophysical Research Communications, March 21, 2016 (abstract)
4. Magnano, L. et al., “Prognostic impact of serum heavy/light chain pairs in patients with monoclonal gammopathy of undetermined significance and smoldering myeloma: long-term results from a single institution” in Clinical Lymphoma, Myeloma And Leukemia, February 26, 2016 (abstract)
5. Park, J. et al., “Oral proteasome inhibitor with strong preclinical efficacy in myeloma models” in BMC Cancer, March 24, 2016 (full text: html, pdf)