Good morning, myeloma world.

It's been a very chilly morning here at Myeloma Morning Headquarters. After teasing us with summerlike temperatures the past few weeks, Mother Nature has decided she's not done with the part of the thermometer below freezing.

We'll be focusing on two new research studies in today's report.

The first study looks at outcomes of allogeneic (donor) stem cell trans­plan­ta­tion for multiple myeloma. Using outcomes from a single U.S. treatment center, the study authors find that whether or not an allo­geneic trans­plant patient had high-risk disease at diagnosis did not have a strong impact on the patient's survival. They also find that, in patients who achieved a complete response after their transplant, minimal residual disease status did not affect a patient's survival.

The second study is a survey article. It describes the challenges that can arise when treating older multiple myeloma patients , and what can be done to improve treatment outcomes in such patients.

High-Risk Disease And MRD Status In Allogeneic Transplantation

Our study today on allogeneic (donor) transplantation in multiple myeloma patients is the second study on this topic that that we have looked at in less than a week. We discussed a Dutch study about allogeneic transplantation in last Friday's edition of Myeloma Morning.

In today's study, researchers from Medical College of Wisconsin examine the impact on survival outcomes of high-risk chromosomal abnormalities and minimal residual disease status post transplant (abstract).

(The term "minimal residual disease" (MRD) is used to describe the presence of small numbers of myeloma cells in a patient's body even after the patient has achieved a deep response to treatment. Patients who have no detectable myeloma cells are described as being “MRD-negative.” Patients with at least some myeloma cells in their samples are categorized as “MRD-positive.”)

The study by the researchers from Medical College of Wisconsin is based on data for 77 myeloma patients who received allogeneic transplants at their institution between 2002 and 2013. The median age of the patients at the time of the transplant was 53 years.

All patients except one had a prior autologous (own) transplant; 34 percent received the allogeneic trans­plant as part of their initial therapy (they underwent a planned tandem “auto-allo” transplant), 66 percent received the allogeneic trans­plant at relapse.

Ninety percent of patients received stem cells from a matched sibling, 10 percent from unrelated donors. The majority of patients (86 percent) received non-myeloablative / reduced-intensity conditioning prior to the trans­plant, 14 percent received myeloablative regimens.

Overall, 35 percent of patients had high-risk chromosomal abnormalities at diagnosis, which the researchers defined as having t(4:14), 17p deletion, a chromosome 1 abnormality, or t(14:16)).

At the time of the allogeneic transplant, 22 percent of patients were in complete remission.

Median follow up of survivors was 50 months.

Across all 77 patients in the study, the five-year progression-free survival was 38 percent, and the five-year overall survival was 59 percent.

There was no statistically significant difference in either progression-free survival (39 percent versus 55 percent at 3 years) or overall survival (50 percent versus 67 percent at 3 years) between patients with high-risk and standard-risk chromosomal abnormalities. There was, however, a trend to overall survival being higher in patients who did not have high-risk chromosomal abnormalities.

The researchers also did not observe any statistically significant impact of minimal residual disease status on progression-free survival or overall survival in patients who had a complete response after their transplant. The 3 year progression-free survival and overall survival for MRD negative versus positive patients were 63 percent versus 38 percent and 78 percent versus 60 percent, respectively. We'll note once again, however, that there was a trend in the results that is worth reporting, which is that MRD seemed to affect progression-free survival (but not overall survival).

Interestingly, there also was a trend in the data for patients who did their transplants at relapse to have both longer progression-free survival and longer overall survival. The authors do not discuss why this might have been the cases.

The authors found that, generally, older age, achieving less than a complete response to treatment prior to the allogeneic trans­plant, and CMV reactivation (reactivation of the herpes virus), were associated with shorter survival.

The cumulative rate of non-relapse mortality, a measure of how dangerous a treatment can be, was 13 percent at one year post transplant. Achieving less than a complete response prior to the donor trans­plant also was associated with a higher risk of non-relapse mortality.

Based on their findings, the researchers conclude that allogeneic transplants benefit younger patients and those in complete remission at the time of their transplant. They added that the comparatively poor prognosis for patients with high-risk chromosomal abnormalities may be overcome by donor stem cell transplantation.

Improving Treatment Outcomes For Older Multiple Myeloma Patients

The second study we will look at today is a survey article written by five myeloma specialists. The authors – who are based at treatment centers in Italy, the United Kingdom, and United States – describe “nuances” in the treatment of older multiple myeloma patients. Keeping these nuances in mind, they say, can help improve treatment outcomes in older patients (abstract).

The researchers never explicitly define what they consider to be "older" myeloma patients, but one could infer they patients older than 65 or 70. This is, of course, a significant share of myeloma patients – more than half, in fact, if 65 is used as the defining characteristic for "older."

The authors begin the discussion in their article by noting that age is not the only factor that should affect treatment choices when it comes to older myeloma patients. Other factors that need to be considered include a patient's overall physical strength, their cognitive abilities, and other diseases they may have. Myeloma specialists have worked on the development of “frailty” assessment tools to capture these factors and incorporate them into treatment decisions.

For newly diagnosed patients, the authors note that three-drug treatment regimens are common in younger patients in the United States and elsewhere. They also have been common in the past among older patients outside the United States.

The authors believe there is a trend, however, toward the use of two-drug regimens – particularly Revlimid (lenalidomide) combined with low-dose dexamethasone – in many older patients.

The authors do see a role, however, for three-drug regimens – particularly three-drug regimens that do not include either melphalan or cyclophosphamide (Cytoxan). Such "alkylator-free" regimens, the researchers say, can be appropriate for older patients who are more fit.

The authors also believe that monoclonal antibody therapies may be a particularly attractive option for older myeloma patients due to such therapies having fewer side effects.

The authors do devote some time to options for treating relapsed older patients, but recognize that decision making for these patients is complex. It depends not only on the choice of a patient's initial therapy, but also the patient's response to initial treatment, the side effects they experienced, and differences in the availability of treatments.

The last part of the survey focuses on recommendations by the authors for how to deal with specific side effects that can occur during the treatment of older myeloma patients. Addressing such side effects – particularly when they are severe – can be especially important in older patients, the authors argue, because older patients cannot recover as well as younger patients from major health setbacks.

Dose reduction or treatment discontinuation should always be considered when significant side effects develop, the authors note. In addition, they discuss steps that can be taken to address anemia, neutropenia, thrombocytopenia (low platelet count), reduced kidney function, neuropathy, blood clots, rash, and diarrhea.

New Myeloma-Related Research Articles

1. Dhakal, B. et al., “Allogeneic hematopoietic cell transplantation in multiple myeloma: impact of disease risk and post allograft minimal residual disease on survival” in Clinical Lymphoma, Myeloma & Leukemia, March 30, 2016 (abstract)
2. Martino, M. et al., “Italian consensus conference for the outpatient autologous stem cell transplantation management in multiple myeloma” in Bone Marrow Transplantation, April 4, 2016 (abstract)
3. Pawlyn, C. et al., “Nuances in the management of older people with multiple myeloma” in Current Hematologic Malignancy Reports, April 2, 2016 (abstract)
4. Russell, D. J. et al., “Orbital plasmacytoma mimicking an orbital abscess” in Ophthalmic Plastic & Reconstructive Surgery, April 4, 2016 (abstract)