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[ by Julie Shilane | Nov 23, 2013 9:04 am | 3 Comments ]

As The Beacon continues its ‘ASH Preview’ series about myeloma re­search that will be presented at the American Society of Hematology (ASH) meeting in early December, this article focuses on novel im­muno­therapy approaches that are being studied in clinical trials.

Abstracts for the ASH presentations are now available, although many contain pre­lim­i­nary information that will be updated at the meet­ing.

The Beacon’s ASH preview articles are intended to highlight the meet­ing’s most interesting myeloma-related studies.

The first several of the preview articles, which were published over the past …

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Results from a retrospective study demonstrate that a set of protein bio­markers found in urine can be used to predict the development of acute graft-versus-host disease in patients who undergo donor stem cell trans­plan­ta­tion.

During the study, levels of specific urine proteins were used to generate a "classi­fication factor," named aGvHD_MS17, designed to predict a pa­tient's probability of developing acute graft-versus-host disease (GVHD).

The study's findings may allow for early detection and preemptive treat­ment of acute GVHD, a potentially fatal complication that can occur after trans­plan­ta­tion using donor stem cells.

“The most …

Opinion»

In last month’s column, I wrote about how much my perspective on myeloma therapy has changed over the past six years since my diagnosis.  In a nutshell, I’m more willing to try new things and endure troubling side effects now than I was back when I was still a “rookie.”

My attitude about stem cell transplants is a perfect example of this.  I look at stem cell transplants differently now – both allogeneic transplants (using donor stem cells) and autologous transplants (using my own stem cells).  Not only would I be …

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Results from a recent small Phase 3 clinical trial show that the use of Velcade in preparation for donor stem cell transplantation as well as its use soon after transplantation and as maintenance therapy may be effective in high-risk multiple myeloma patients.

The results also indicate that the use of Velcade (bortezomib) soon after donor trans­­plan­­ta­­tion reduces the risk of developing a life-threatening donor trans­plant-related complication known as graft-versus-host disease.

The researchers note that, similar to other donor transplant protocols, the relapse rate was high. Thus, they recommend study of other novel …

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Revlimid Plus Dexamethasone Extends Progression-Free Survival In Newly Diagnosed Multiple Myeloma Patients – Results of a large international Phase 3 trial show that Revlimid (lenalidomide) plus dexamethasone (Decadron) ex­tends progression-free survival in newly diagnosed multiple myeloma patients who are not eligible for autologous stem cell transplantation, compared to treat­ment with melphalan (Alkeran), prednisone, and thalidomide (Thalomid). Based on these findings, Celgene, the manufacturer of Revlimid, will start the pro­cess of applying for approval of Revlimid as frontline treat­ment in the United States, Europe, and other countries. Although Celgene is widely used in the U.S. for the treatment of newly diagnosed myeloma patients, it is not officially approved for that use in the U.S. or any other country.  For more information, please see the related press release from Celgene.

Order Of Velcade And Revlimid Treatment May Not Matter In Treating Myeloma – Results from a recent retrospective study indicate that multiple myeloma patients benefit equally whether they are treated with Velcade (bortezomib) before Revlimid, or vice versa. However, patients with kidney disease tend to benefit from earlier use of Velcade-based therapies. Both Revlimid- and Velcade-based therapies have become common treatment options for myeloma patients. The investigators of this study were interested in de­ter­min­ing whether one drug should be given before the other. In their analysis, which was based on data for 208 myeloma patients treated between 2003 and 20089, the authors adjusted for a number of potential biases, such as patient age, number of previous therapies, and whether or not a patient had received a stem cell transplant.  The researchers found no significant difference in median overall survival between patients who received Revlimid first versus those who received Velcade first. For more information, please refer to the study in the journal Leukemia Research (abstract).

Unrelated Donor Stem Cell Transplant May Be An Under-Utilized Treatment Option For Myeloma – Find­ings from a retrospective study suggest that donor stem cell transplants using cells from unrelated donors may be underutilized for myeloma patients, particularly older myeloma patients. Specifically, the researchers found that only 11 percent of the myeloma patients they estimated to be eligible for an unrelated donor trans­plant actually underwent the procedure. Reasons for not undergoing a transplant included not being referred to a transplant center, worsening health condition of the patient, a prolonged search for a suitable donor, and financial issues. Donor (allogeneic) stem cell transplants involve infusing a patient with donor stem cells after high-dose chemotherapy. While the procedure has the potential to cure myeloma, it also is often accompanied by serious complications, including graft-versus-host-disease (GVHD), in which donor im­mune system cells recognize the patient's cells as foreign and attack them. For more information, please re­fer to the study in the journal Biology of Blood and Marrow Transplantation (ab­stract).

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Hybrid Drugs Based On Thalidomide And Curcumin May Be A Future Treat­ment Option For Myeloma Patients – Results from a recent preclinical study indicate that hybrid molecules combining chemical structures from thal­ido­mide (Thalomid) and curcumin may be potential treatments for multiple myeloma. Specifically, the investigators found that two particular hybrid mole­cules were effective in killing myeloma cells and were safer than either drug alone. Cur­cu­min is the major active compound in turmeric, a popular Indian spice. Several early-stage studies have investigated curcumin's potential as a myeloma treat­ment (see related Beacon news articles). Ac­cord­ing to the re­search­ers, hybrid drug therapy, which involves combining elements from two or more drugs into one molecule, is a promising treatment option for myeloma because it may be be safer and associated with a reduced risk of developing drug resistance. For more information, please refer to the study in the journal Organic and Bimolecular Chemistry (abstract).

Tandem Autologous Stem Cell Transplants May Not Cause Serious Heart Problems – Results from a small, retrospective Slovenian study suggest that two back-to-back, or tandem, autologous stem cell trans­plants (using the patient’s own cells) may not cause serious heart problems in the long-term. The study in­cluded 12 patients, each of whom received cyclo­phos­pha­mide (Cytoxan) for stem cell mobiliza­tion, and then high-dose chemotherapy with melphalan (Alkeran) prior to each transplant.  None of the patients de­vel­oped critical heart issues six years after their tandem transplant.  However, the re­search­ers did detect some signs of heart damage in the more detailed tests they carried out.  Thus, the authors recommend long-term follow-up studies with tandem transplant patients, in part because of the increasing life expectancy of myeloma patients. For more information, please see the study in journal Radiology and Oncology (full-text).

Methotrexate-Cytarabine Combination May Be Useful For Stem Cell Remobilization – Results from a small study conducted in South Korea indicate that a combination of high-dose methotrexate and cytarabine (Cyto­sar-U) plus granulocyte colony-stimulating factor (G-CSF) may be a useful alternative for stem cell mobili­za­tion.  Cytarabine is an older chemo­thera­py drug which has been used in the treatment of certain leukemias and lymphomas.  Methotrexate also is an older drug, which has been used in high doses as a chemo­thera­py agent, and in low doses to treat various auto­immune dis­orders, including rheuma­toid arthritis.  The Ko­re­an study included eight patients who had previously failed to mobilize sufficient stem cells using regimens including G-CSF and conventional chemo­therapy agents.  Of those eight patients, all but one were able to mobilize a sufficient number of stem cells using the methotrexate-cytarabine-G-CSF combination. The re­search­ers point out that larger studies are necessary to confirm their findings. For more information, please refer to the study in the journal Transfusion (abstract).

Donated, Virus-Specific White Blood Cells Effective For Severe Viral Infections After Donor Trans­plan­ta­tion – Results of a recent study show that donated t-cells, a type of white blood cell, can be used to treat severe viral infections in patients who have undergone allogeneic (donor) stem cell trans­plan­ta­tion.  During the study, virus-specific t-cells were collected from individuals who were immune to certain viral infections. The do­nated t-cells were then used to treat a total of 50 patients who had undergone a donor stem cell trans­plant and then developed a severe viral in­fec­tion.  In 74 percent of the cases, the donated t-cell treat­ment led to either a partial or complete elimination of the viral infection.  According to the researchers, the treatment was well tolerated; there were no infusion-related side effects, and only 4 percent of the patients developed graft-versus-host disease after the t-cell infusions.  Graft-versus-host disease is a com­pli­ca­tion that arises when donor cells identify the recipient cells as foreign and attack them. For more information, please the study in the journal Blood (full text).

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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).