A happy Saturday to you, myeloma world.

We hope your weekend has gotten off to an excellent start.

Today's edition of Myeloma Morning focuses primarily on a study that was included in yesterday's list of new myeloma-related research. The study summarizes trends in allogeneic (donor) stem cell transplantation in Europe over the last two decades.

Although the study focuses on European trends, we believe it should be of interest to Beacon readers regardless where they may be. With the global exchange of information related to multiple myeloma, trends in Europe are not happening in isolation. They reflect, and also influence, trends elsewhere.

Readers also should be sure to check the "Quickly Noted" section at the end of today's report. It includes short descriptions of three studies included in today's list of new myeloma-related research. We'll be reporting on one of those studies in more detail in the coming days.

Allogeneic Stem Cell Transplantation In Europe Since 1990

A group of European researchers has published a study summarizing trends in allogeneic (donor) trans­planta­tion for multiple myeloma in Europe since 1990 (abstract).

The researchers analyzed data from 7,333 multiple myeloma patients who received an allogeneic transplant between January 1990 and December 2012 and whose data was reported to the registry of the European Society for Blood and Marrow Transplantation (EBMT). The median age of the patients at the time of their allogeneic transplant was 51 years.

For their analysis, the researchers divided patients into three groups based on the timing of their allo transplant:

1. Group 1 included 1,924 patients who received an allogeneic transplant upfront after induction therapy
2. Group 2 included 2,004 patients who received an allogeneic transplant upfront as part of autologous-allogeneic tandem transplantation, with a maximum interval of 8 months between the auto and allo transplant
3. Group 3 included 3,405 patients who received an allogeneic transplant at a later time after one, two or three autologous transplants with at least 8 months between the first autologous and the allogeneic transplant; in this group, the allogeneic transplant was performed mainly as second-line treatment and beyond.

All three groups were further divided into two subgroups based on when the transplant was carried out: those who received their allogeneic transplant before 2004, and those who received it after 2004. The researchers chose this date because it was the time when novel multiple myeloma therapies started to become available throughout Europe.

At the time the data for the study were analyzed, 3,140 patients were still alive with a median follow-up of 36 months after the date of transplantation.

Changes In Who Receives Allogeneic Transplants

Overall, the researchers observed a steady increase in allogeneic transplants over time, with the maximum number performed in 2012.

However, there was a significant shift over time in which patients received allogeneic transplants.

Prior to the year 2000, most allogeneic transplants in European multiple myeloma patients were upfront transplants. However, the number of these transplants actually declined in absolute numbers after the year 2000, and accounted for just 12 percent of all allogeneic transplants performed in 2012.

The peak significance of allogeneic transplants done as part of a tandem transplant was around 2004, and by 2012 such transplants were 19 percent of all allogeneic transplants for multiple myeloma in Europe.

The use of allogeneic transplantation later in a patient's treatment became the dominant timing of allogeneic transplantation by the end of the period covered by the study, reaching almost 70 percent in 2012.

Differences In Allogeneic Transplantation Across Countries

The researchers found that the distribution of allogeneic transplantation across the three groups of patients varied significantly across countries in Europe. In recent years, for example, Germany has been the only major country where a significant share of patients receive tandem auto-allo transplants. In addition, in most countries other than the United Kingdom and Germany, allogeneic transplants are typically reserved for the third group of patients – those who have relapsed after other treatments.

The authors attributed this variation across countries to be due to possible differences in health care reimbursement policies as well differences in the policies of national multiple myeloma study groups (such as the IFM in France, HOVON in the Netherlands, and the GMMG in Germany).

Response Status At Transplantation, Conditioning Regimen, And Stem Cell Source

Response status at the time transplantation was available for 93 percent of patients. For patients who received their allogeneic transplants after 2004, 26 percent of patients in group 1, 29 percent in group 2, and 27 percent in group 3 had achieved at least a very good partial response (VGPR) at the time of their allogeneic transplant. These rates of VGPR achievement may not seem very high, but they are noticeably higher than what they were before 2004, when the rates were just 14 percent in group 1, 17 percent in group 2, and 9 percent in group 3.

In the early years of the period covered by the study, myeloablative conditioning was the only form of conditioning used. There was a dramatic shift around 2000, however, toward reduced-intensity conditioning. This, the authors believe, increased the use of allogeneic transplantation among older and less physically fit patients. In 2012, reduced-intensity conditioning was used in two thirds of all allogeneic transplants in the European database.

The researchers observed a similar shift over the study period in regard to stem cell donors. In the early years, stem cells typically came only from related donors. In recent years, the use of stem cells from unrelated donors increased significantly, reaching 56 percent in 2012.

Improvements In Survival And Transplant Safety

In regard to overall survival measured from the time of the allogeneic transplant, the researchers found that it increased from the period before 2004 to the period after 2004. Median overall survival increased from 29 months in the earlier period to 40 months in the later period in the upfront allogeneic transplant group. The increase was from 63 months to 70 months in the tandem auto-allo transplant group, and from 16 months to 26 months in the later allo transplant group.

Progression-free survival improved significantly after 2004 in the auto-allo transplant group and the later allogeneic transplant group, increasing from 20 months to 24 months, and from 7 months to 11 months, in the two groups, respectively. The researchers attribute this increase to the introduction of novel agents for the treatment of multiple myeloma. The difference in progression-free survival in the upfront allogeneic transplant group, however, was not statistically significant, changing from 14 months to 16 months.

Non-relapse mortality, a measure of how dangerous a treatment can be, decreased after year 2004 compared to before 2004 in the upfront allogeneic transplant group (from 36 percent to 30 percent at three years post transplant) and in the later allogeneic transplant group (from 35 percent to 29 percent). However, it remained similar at 19 percent in the two time periods for the tandem auto-allo transplant group.

Quickly Noted

There are three studies in our list of new research articles below that we want to mention briefly before wrapping up this report.

First, there's an important study published in the journal Blood by researchers mainly associated with the Dana-Farber Cancer Institute in Boston. It concerns the role of the “B cell maturation antigen” (BCMA) and associated molecules in the proliferation of multiple myeloma and the resistance of the disease to treatment (abstract). We will look at this article in more detail in an upcoming edition of Myeloma Morning.

Second, a study by researchers in France finds that PET/CT imaging done with the 18F-fluorocholine (FCH) tracer may be better at detecting relapse and/or disease progression in multiple myeloma patients than the standard 18F-fluorodeoxyglucose (FDG) tracer (abstract). Regular readers of Myeloma Morning may recall our reminding readers of the potential value of other tracers in PET/CT for myeloma in a previous edition of this report.

Finally, German researchers have published a meta-analysis of the results of clinical trials in which the participants were newly diagnosed multiple myeloma patients ineligible for a stem cell transplant. The analysis indicates that treating transplant-ineligible patients with the combination of Revlimid (lenalidomide) and dexamethasone may lead to superior survival outcomes compared to other treatment regimens commonly used in such patients (full text).

New Myeloma-Related Research Articles

1. Cassou-Mounat, T. et al., “18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study” in the European Journal of Nuclear Medicine and Molecular Imaging, April 28, 2016 (abstract)
2. Ganai, S. A., “Histone deacetylase inhibitor givinostat: the small-molecule with promising activity against therapeutically challenging haematological malignancies” in the Journal of Chemotherapy, April 28, 2016 (abstract)
3. Kitahata, S. et al., “Design, synthesis, and biological activity of isosyringolin A” in Organic Letters, April 28, 2016 (abstract)
4. Tai, Y. T. et al., “APRIL and BCMA promote human multiple myeloma growth, chemoresistance, and immunosuppression in the bone marrow microenvironment” in Blood, April 28, 2016 (abstract)
5. Vanstechelman, S., Vantilborgh, A. & Lemmens, G. “Dexamethasone-induced catatonia in a patient with multiple myeloma” in Acta Clinica Belgica, April 28, 2016 (abstract)
6. Weisel, K. et al., “A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation” in Leukemia & Lymphoma, April 28, 2016 (full text)