Good morning, myeloma world.

It's another rainy day here at Myeloma Morning Headquarters, and we're trying to stay positive by keeping in mind that old rhyme, “April showers bring May flowers.”

“Rain is good,” we keep telling ourselves. “Rain is good.”

But we're not so sure, so we're turning our attention to our main task today, which is getting you up to speed on what's new in myeloma world.

In that regard, we'll be focusing first on a brief study by myeloma special­ists at the Mayo Clinic. They've investigated the treatment and survival out­comes of myeloma patients who underwent at least one autol­o­gous (own) stem cell transplant after diagnosis at their treatment center.

We also have information about a short report by Ohio State researchers. They describe their use of Soliris (eculizumab) to treat thrombotic micro­angi­opathy (TMA) when it developed in five patients who had under­gone an allogeneic (donor) stem cell transplant. Regular Myeloma Morning readers will recall that we've discussed TMA in previous editions of this report. It is a potential side effect of certain myeloma therapies.

Finally, myeloma specialist Dr. Leif Bergsagel has some feedback for us on the preclinical myeloma therapy CCF642, also mentioned in a previous Myeloma Morning. And we have several “Quickly Noted” items to wrap up today's update.

Outcomes After A Myeloma Patient's First Autologous Stem Cell Transplant

The first study we'll discuss is a brief report written by researchers at the Mayo Clinic's Rochester, Minnesota campus. Their study describes treatment outcomes for a sequential series of 672 multiple myeloma patients who had a first autol­o­gous stem cell transplant at their treatment center sometime between January 1, 2000 and December 31, 2012. The authors focus, in particular, on time to relapse after first transplant, and its link with a patient's overall survival (abstract).

Seventy percent of the patients had an “early” transplant – that is, a transplant within a year of their multiple myeloma diagnosis. The median age at the time of transplantation was 60, and all patients were treated at some point with a novel myeloma therapy, such as Revlimid (lenalidomide) or Velcade (bortezomib). How­ever, only 60 percent of the patients in the study had a novel therapy during their initial treatment. Also, only 13 percent of the patients started maintenance therapy after their transplant.

Although the researchers investigate several topics during the course of their article, a key focus is on time to relapse after a patient's first transplant, and whether or not time to relapse is linked to a patient's overall survival. They investigate this link separately for patients who had an early transplant and those who had a delayed transplant.

(We believe it worth reminding our readers at this point that this study's results are based, in part, on multiple myeloma patient experiences from more than 10 years ago. Since then, at least six new myeloma therapies have been introduced. Collectively, these new treatment options have significantly expanded myeloma patient survival beyond what it was during much of the period covered by this study.)

In patients who had an early transplant, the Mayo researchers found that those who relapsed within two years of their first transplant lived a median of another 29 months after that relapse. Those who relapsed more than two years after their first transplant lived a median of another 60 months after relapse.

In patients who had a delayed transplant, the researchers found that survival post relapse was a median of 23 months for those who relapsed within two years of their transplant, and a median of 66 months for those who relapsed more than two years after their transplant.

The Mayo researchers do not address in their article whether their results have any bearing on the early-versus-late stem cell transplantation debate in multiple myeloma.

Soliris (Eculizumab) For Thrombotic Microangiopathy (TMA)

We turn next to a short report by researchers at The Ohio State University. They describe their use of the medication Soliris to treat five patients who developed thrombotic microangiopathy (TMA) after undergoing allogeneic stem cell transplantation (abstract).

None of the patients in the Ohio State study had multiple myeloma. Three of the patients had forms of leukemia, and two had severe aplastic anemia. We mention this study, however, because TMA is a rare side effect of certain myeloma therapies, including the high-dose melphalan administered during the autologous (own) stem cell transplantation process. We also noted in a previous edition of Myeloma Morning that Soliris may be a possible treatment for TMA.

The researchers from Ohio State report that four out of their five patients showed improvement in platelet counts and kidney function – signs of recovery from TMA – after treatment with Soliris. In addition, the researchers note that TMA appeared to cause heart- and lung-related problems, and these seemed to clear with Soliris treatment.

Nevertheless, two of the five patients died, both of infections. Moreover, although the infections in these patients were not necessarily due to Soliris, the drug can increase a patient's risk of developing an infection.

The study authors are understandably hesitant to draw any conclusions based on data for just five patients. They do appear, however, to feel that Soliris offers promise as a treatment for TMA. They note, for example, that their study “validates” a previous study that reported positively on the use of Soliris for TMA in very young stem cell transplant patients (full text).

More About CCF642

We reported a few days ago in Myeloma Morning about the drug CCF642. In particular, we discussed a study with results of preclinical research investigating CCF642 as a potential anti-myeloma therapy.

Since our article about the CCF642 study, we have gotten feedback about the study from myeloma specialist Dr. Leif Bergsagel of the Mayo Clinic. Dr. Bergsagel told us:

“I find the paper about CCF642 very interesting. I agree with the authors that targeting the high protein secretion by multiple myeloma cells is a unique vulnerability that should be exploited. Probably this is one of the reasons for the selective activity of proteasome inhibitors in multiple myeloma. Some un­pub­lished research from my colleague Dr. Rafael Fonseca suggests this may be one of the ways IMiDS [immunomodulatory agents, such as Revlimid and thalidomide] are working as well.

“I think protein disulfide isomerase is a good target. As for CCF642, it was identified using a large screen, and the drugs that come out of large screens typically do not work in patients. Optimization needs to be done.

“The other thing is none of the preclinical models the authors use in their study really secrete very much immunoglobulin. You need to use either primary patient samples, or the Vk*MYC multiple myeloma mouse model, in order to model cells with high protein secretion. So the data are very preliminary.”

Dr. Bergsagel is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research at the Mayo Clinic in Scottsdale, Arizona. He also is co-developer of the Vk*MYC multiple myeloma mouse model mentioned in his feedback above about the CCF642 study.

Quickly Noted

• One of the genes thought to play an important role in multiple myeloma is known as FAM46C. It is part of the FAM46 family of genes. Now, researchers in Poland report that “FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma” (full text)
• Beacon columnist Andrew Gordon recently compiled a list of research articles related to secondary MGUS in multiple myeloma patients. He's shared the list with Beacon readers in a posting in the Beacon's forum.
• Debbie recently posted a Day +23 stem cell transplant update in the forum. She had problems when her doctors tried to reduce the dose of prednisone she's been receiving, but she's doing better now.
• If you're the kind of person inclined to ask, “Where did that April showers/May flowers rhyme come from?”, allow us to suggest you not go down that rabbit hole. You'll end up somewhere in the mid 1500s, and you still won't be 100 percent certain you have the right answer.

New Myeloma-Related Research Articles

1. Gonsalves, W. I. et al., “Clinical course and outcomes of patients with multiple myeloma who relapse after autologous stem cell therapy” in Bone Marrow Transplantation, April 11, 2016 (abstract)
2. Kuchta, K. et al., “FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases” in Nucleic Acids Research, April 7, 2016 (full text)
3. Vasu, S. et al., “Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy” in Bone Marrow Transplantation, April 11, 2016 (abstract)