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It's good to see you again, myeloma world.

We got tied up the past couple days with, among other things, coverage of the Empliciti approval in Europe. But we're glad to be back and we have two new research studies that we'd like to discuss with you.

First, we take a look at an Israeli study that does a deep dive into the t(11;14) chro­mosomal abnormality in newly diagnosed multiple myeloma patients. The focus of this particular deep dive is the impact other chro­mosomal abnormalities have on the prognosis of newly …

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How has your week started, myeloma world?

We hope it's going well so far.

We once again have a rather long list of new myeloma research we'd like to discuss with you. We sus­pect most of our readers will find at least one or two studies in the report to be of particular interest.

We begin today's report with a discussion of a somewhat rare eye-related side effect of Velcade (bor­tez­o­mib) and a possible way to control the side effect.

Next, we take a quick look at two articles about …

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BMI, Not Physical Activity, Associated With Risk Of Myeloma – Results of a large U.S.-based study sponsored by the AARP found that across all age groups, people with higher body mass index (BMI) were more likely to develop multiple myeloma.  However, physical activity level at any age did not impact the likelihood of developing myeloma.  Previous studies have investigated whether obesity increases a person’s risk of developing myeloma, but the results have been inconsistent.  For more information, see the study in American Journal of Epidemiology (abstract).

Study On Timing Of Stem Cell Transplantation Shows Early Transplant Improves Progression-Free Survival – Results from a small, retrospective study conducted in China show that newly diagnosed myeloma patients who received Velcade (bortezomib)-based initial therapy and a stem cell transplant had significantly longer progression-free survival (42 months) compared to previously-treated patients who received the same combination of treatments at relapse (27 months).  Although there was not a statistically significant difference in overall survival between the two groups of patients, there was a trend favoring early transplantation: five years from diagnosis, about 80 percent of the early-transplant patients were still alive, versus about 50 percent of the delayed-transplant patients.  The trend to better survival in the early-transplant group, however, may be due to the fact that all patients in this group received a novel therapy (Velcade) as part of their initial therapy immediately after diagnosis.  This was not the case for the late-transplant patients, some of whom received older treatment regimens as their initial treatment immediately after diagnosis.  In both groups of patients, stem cell transplantation deepened the response to treatment.  The transplant process increased the combined rate of near-complete and complete responses from 70 percent to 85 percent in the early-transplant patients, and from 56 percent to 81 percent in the late-transplant patients.  For more information, see the study in the Chinese Journal of Cancer Research.

Study Sheds Light On Efficacy And Safety Of Preparative Therapy For Donor Stem Cell Transplantation – An Italian study of 196 myeloma patients who underwent donor (allogeneic) stem cell transplantation com­pared the outcomes of those who received myeloablative preparative therapy (high-intensity treatment that causes irreversibly low blood cell counts and requires stem cell transplantation) versus reduced-intensity prepara­tive therapy (causes low blood cell counts and should be accompanied by stem cell trans­plan­ta­tion) versus non-myeloablative preparative therapy (causes minimal reductions in blood cell counts and does not need to be accompanied by stem cell trans­plan­ta­tion).  All transplants were done using stem cells donated by unrelated donors.  Patients had received a median of three lines of therapy prior to their donor transplant, and 89 percent of the patients had previously undergone at least one autologous (own) stem cell transplant.  The results of the study show that patients who received non-myeloablative or myeloablative thera­py had longer event-free and overall survival than those who received reduced-intensity therapy.  Event-free survival was 10 months for those who received myeloablative therapy, 6 months for reduced-intensity thera­py, and 13 months for non-myeloablative therapy.  Overall survival was 29 months, 11 months, and 32 months, respectively.  However, patients who received myeloablative therapy were most likely to experience fatal transplant-related complications.  The one-year treatment related mortality rates were 29 percent for myelo­ablative therapy, 20 percent for reduced-intensity therapy, and 25 percent for non-myeloablative thera­py.  At three years, the rates were 37 percent, 31 percent, and 30 percent, respectively.  The study investi­ga­tors conclude that long-term disease control is still challenging and that more studies are needed to de­fine the role of donor transplantation for myeloma using stem cells from unrelated donors.  For more infor­ma­tion, see the study in Biology of Blood and Marrow Transplantation (abstract).

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Entinostat And Treanda Enhance Each Other’s Efficacy Against Myeloma Cells – Results from a recent preclinical study show that Treanda (bendamustine) and the investigational drug entinostat (SNDX-275) enhance each other’s efficacy against multiple myeloma cells.  The two drugs, when given together, were more effective than expected based on the efficacy of either drug alone. Entinostat is an oral treatment that belongs to a family of anti-cancer drugs called HDAC inhibitors. Other HDAC inhibitors under investigation for multiple myeloma include Zolinza (vorinostat) and panobinostat.  Entinostat is currently being studied in clinical trials for patients with leukemia and breast cancer.  A Phase 1 study of Entinostat in myeloma patients and other blood cancer patients was recently completed, but the results have not been published yet. Treanda is approved in the United States as a treatment for chronic lymphocytic leukemia and certain lymphomas, and it is being investigated as a treatment for myeloma. It belongs to a class of drugs known as alkylating agents, which also includes melphalan (Alkeran) and cyclophosphamide (Cytoxan). These drugs damage the DNA of cancer cells, triggering their death. For more information, please refer to the study in Cancer Letters (abstract).

Low Levels Of Adiponectin May Be Associated With A Higher Risk Of Developing Myeloma – Findings from a prospective study show that low levels of the protein adiponectin may be associated with a higher risk of developing multiple myeloma. Adiponectin regulates glucose levels in the blood and is found at lower levels in people who have type-2 diabetes or who are obese. The investigators of the current study compared the levels of different proteins known as adipokines in 174 myeloma patients and 348 healthy individuals. They found that myeloma patients had lower levels of adiponectin than healthy individuals. Based on their findings, the researchers recommend further study of adiponectin as a possible therapeutic target for myeloma. For more information, please see the study in Cancer Epidemiology, Biomarkers, and Prevention (abstract).

Etoposide, Thiotepa, and Melphalan May Be More Effective Than Melphalan Alone – Results from a recent Israeli study show that treatment with etoposide (VP-16), thiotepa, and melphalan may be more effective than melphalan alone prior to stem cell transplantation. In particular, patients who received the three-drug combination had a longer time to progression (44 months versus 17 months) and longer overall survival (not yet reached after a median of 108 months follow-up versus 59 months) than those who received melphalan alone. However, the researchers said that based on the small number of patients included in the study, the three-drug combination appeared to be slightly more toxic than melphalan alone. The investigators still believe that the three-drug combination can be effective in certain myeloma patients receiving a stem cell transplant. Etoposide is a chemotherapy drug used as a treatment for lung and testicular cancer. Previous studies have shown that etoposide is highly effective in mobilizing stem cells. Thiotepa, like melphalan, is an alkylating agent that damages the DNA of cancer cells. For more information, please refer to the study in the journal Leukemia and Lymphoma (abstract).

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Results of a recent study indicate that obesity does not negatively affect outcomes after stem cell transplantation in multiple myeloma patients. In fact, obese patients treated with high-dose melphalan-based chemotherapy and total body irradiation before transplantation had a lower risk of relapse and better overall survival, compared to normal-weight patients.

The study authors concluded that obese multiple myeloma patients should not be excluded from stem cell transplantation due to their weight.

“Obese patients don't seem to be at higher risk for severe side effects from transplant compared to patients of normal weight, and they …

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