Good morning, myeloma world.

It's a glorious spring morning here at Myeloma Morning Headquarters. The sun is coming up in the midst of a clear blue sky, and the cherry tree out front is bursting with blossoms.

In other words, it's a great day to get excited about new multiple myeloma research and other myeloma-related developments.

First, we take a look at a new study by researchers at the John Theurer Cancer Center (JTCC) in New Jersey. They examine whether Pomalyst (pomalidomide, Imnovid) can be used safely in relapsed myeloma patients with impaired kidney function (abstract).

Now, before we go any further, we have to point out that the JTCC study examines findings for just five patients who were treated with Pomalyst. That being said, the patients had significant kidney damage – in some cases to the point of dialysis dependence. In addition, the patients were being treated with Kyprolis (carfilzomib) and dexamethasone at the same time they were being treated with Pomalyst. Some patients also received cyclo­phos­phamide (Cytoxan).

The study authors found that all five patients achieved at least a partial response to the Pomalyst-based therapy, which they described as “relatively well tolerated.” These findings, they go on to write, “suggest that pomalidomide may represent a valuable and tolerable treatment option for multiple myeloma patients with severe renal impairment.”

This new look at Pomalyst-based therapy comes on the heels of an important Pomalyst study published earlier this month, which looked at results of a clinical trial comparing Pomalyst combined with cyclo­phos­phamide and dexamethasone to Pomalyst and dexamethasone alone (abstract).

Next, we turn to two studies that report on markers of disease status and prognosis.

One study is from a group of California researchers, who focus on a type of immunoglobulin test – the so-called “Hevylite” assay – that should be familiar to readers of this past Sunday's edition of Myeloma Morning.

(We'll note right now that the summary of this study is going to go on for more than the usual number of paragraphs. It just takes a while to lay out the background needed to understand Hevylite test results. So, if studies related to such results are not your cup of tea, you'll want to skip ahead to the discussion of the next study we cover.)

As we noted on Sunday, standard immunoglobulin testing reports the total level of a person's IgG, IgA, and IgM. There are, however, two types of each of these kinds of immunoglobulin – kappa and lambda. There is IgG kappa and there is IgG lambda; IgA kappa and IgG lambda; and so on.

The Hevylite test measures the level of each of these specific heavy/light chain levels. It reports the level of a person's IgG kappa, IgG lambda, and the like.

On Sunday, we noted that heavy/light chain results can be useful for estimating how likely someone with asymptomatic multiple myeloma, such as smoldering myeloma, is to progress to symptomatic multiple myeloma requiring treatment.

In the new study by California researchers, the focus is on how heavy/light chain levels correspond with how a multiple myeloma patient has responded to treatment (abstract).

The researchers looked at data for 189 newly diagnosed and relapsed multiple myeloma patients who received treatment at their single treatment center. They focused, in particular, on comparisons of what are known as a patient's “involved” and “uninvolved” heavy/light chain pairs. For someone who has, for example, IgG kappa multiple myeloma, the involved and uninvolved heavy/light chain pair is IgG kappa ("involved") and IgG lambda ("uninvolved").

Some of the results the researchers found are to be expected. In patients who have responded well to treatment, for example, the level of the involved heavy/light chain is not very high. As a result, the difference between the involved and uninvolved heavy/light chain pairs is small for patients who have responded well to treatment, and larger for patients who have not responded so well.

The finding that is more interesting, however, concerns the uninvolved heavy/light chain level. In patients who have not responded well to treatment, this level is typically suppressed -- lower than it is in patients who have had a good response to treatment.

So, in summary, the multiple myeloma in patients who do not response well to treatment not only causes excess production of the involved immunoglobulin subtype; it also suppresses the production of the uninvolved subtype.

The second study related to disease markers is from researchers in Israel. It reports on the connection between a patient's absolute lymphocyte level when they are diagnosed with multiple myeloma and their overall survival (abstract). Lymphocytes are a type of white blood cell that includes natural killer cells (NK cells), T cells, and B cells.

The Israeli researchers looked at data for 62 newly diagnosed multiple myeloma patients. All patients were diagnosed at the authors' treatment center between 2006 and 2014.

The researchers found that, when they looked at data for all the patients in their sample, patients lived longer if they had an absolute lymphocyte count above 1600 per microliter at diagnosis. This finding is in line with previously published studies.

However, when the authors looked at only the patients in their sample who were treated with novel myeloma therapies – that is, therapies such as Velcade (bortezomib) and Revlimid (lenalidomide), which have been introduced in the last 10 or 15 years – they find that the patient's absolute lymphocyte count at diagnosis does not affect overall survival.

The last study that we'd like to mention today is a review article published by a pair of physicians in Oxford, England. The authors review potential new therapies for multiple myeloma that work by either affecting the bone marrow that surrounds myeloma cells, or by affecting the way myeloma cells interact with the surrounding bone marrow (abstract). Some of these therapies may have a direct anti-myeloma effect of their own. Others may significantly boost the anti-myeloma effect of existing therapies.

Some of the new classes of drugs covered in the review include “CXCR4 antagonists, RANKL inhibitors, HIF1α pathway inhibitors, and inhibitors of Notch, Wnt and TGFβ family pathways.”

(Say that three times fast!)

The world of myeloma-related business continues to be quiet these days – at least when it comes to public announcements. The Beacon's discussion forum, in contrast, continues to be very active. Here are some topics that are being discussed, or are just beginning to be active:

• What exactly makes a stem cell transplant an “inpatient” transplant versus an “outpatient” transplant? (link to discussion)
• Do you think radiation may have caused your multiple myeloma? (link to discussion)
• KB has IgG kappa asymptomatic multiple myeloma. Her M-spike recently increased at the same time that her IgG level dropped. She is wondering how that is possible (link to discussion)
• Karen is getting a lot of feedback on her question about when stem cells are reinfused during the autologous stem cell transplant process (link to discussion)
• Gary also has gotten several responses to his question, “How can we care for the caregivers?” Do you have any advice? (link to discussion)

New myeloma-related research articles

1. Gooding, S. et al., “New approaches to targeting the bone marrow microenvironment in multiple myeloma” in Current Opinion in Pharmacology, March 23, 2016 (abstract)
2. Gryshchenko, A. A. et al., “Design, synthesis and biological evaluation of 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones as inhibitors of protein kinase FGFR1” in Bioorganic & Medicinal Chemistry, March 21, 2016 (abstract)
3. Harutyunyan, N. M. et al., “Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients” in the British Journal of Haematology, March 27, 2016 (abstract)
4. Lal, T. R. et al., “Once again, rare diseases provide a spotlight” in Molecular Genetics and Metabolism, March 5, 2016 (abstract)
5. Richter, J. et al., “Safety and tolerability of pomalidomide-based regimens (pomalidomide-carfilzomib-dexamethasone with or without cyclophosphamide) in relapsed/refractory multiple myeloma and severe renal dysfunction: a case series” in Hematological Oncology, March 27, 2016 (abstract)
6. Suriu, C. et al., “Absolute lymphocyte count as a prognostic marker in newly diagnosed multiple myeloma patients” in the International Journal of Laboratory Hematology, March28, 2016 (abstract)