Many new and promising research developments were made in the field of multiple myeloma during 2010. Over the course of the year, The Myeloma Beacon published more than 100 articles on important myeloma-related studies ^[1].

To highlight the most important of these studies from 2010, The Myeloma Beacon surveyed leading physicians and researchers in the field.  They were asked to name the three peer-reviewed journal articles published in 2010 and the three conference presentations from 2010 that have the most important findings or implications relating to multiple myeloma.

Their selections for the top three journal articles and conference presentations are presented below along with several runner-up studies that received a notable number of votes.

Journal Articles

1: Zometa Improves Survival In Myeloma Patients

According to the physicians surveyed, the most important study published in 2010 compared the efficacies of Zometa ^[2] (zoledronic acid) and Bonefos (clodronic acid), bisphosphonates used to treat bone disease in myeloma patients.  Not only was Zometa more effective at reducing bone complications, but it also extended survival by 5.5 months regardless of whether the patients had myeloma bone disease.

The findings are “practice-changing, as patients can receive this drug to improve multiple myeloma overall survival, regardless of bone health status,” wrote Dr. Saad Zafar Usmani, an assistant professor at the University of Arkansas for Medical Sciences who was not involved with the study.

Dr. Gareth Morgan, lead author of the study, recently completed a follow-up study to determine the impact of Zometa on bone disease in patients receiving standard- or high-dose induction therapy. He noted that the patients with the most reduction in bone disease had been treated with immunomodulatory drugs, such as thalidomide ^[3] (Thalomid) or Revlimid ^[4] (lenalidomide).

“Bone health is important in myeloma patients.  The combined use of novel therapies achieving maximum responses combined with Zometa should not only improve survival but also significantly reduce bone disease, improving quality of life,” wrote Dr. Morgan in an email to the Beacon.

For more information, please see the journal The Lancet ^[5] (abstract) and the related Beacon news article ^[6].

2: VTD Induction Therapy Is Superior To TD For Transplant Candidates

In second place, an Italian study compared a three-drug combination of Velcade ^[7] (bortezomib), thalidomide, and dexamethasone ^[8] (Decadron), known as VTD, with a two-drug combination of thalidomide and dexamethasone, known as TD. Participants received one of these regimens as induction therapy, followed by two stem cell transplants using their own stem cells and then VTD or TD again as consolidation therapy. Researchers found that a significantly higher percentage of patients treated with VTD induction responded as compared to those treated with TD (93 percent versus 79 percent).  After stem cell transplantation and consolidation therapy, response rates continued to be higher for the VTD group.

The study “demonstrated the superiority of a three-drug combination of VTD for induction over TD ... and the importance of induction therapy for patients who are proceeding to transplant,” wrote Dr. William Bensinger, a professor of medicine at the Fred Hutchinson Cancer Research Center in Seattle.

For more information, see the journal The Lancet ^[9] (abstract) and the related Beacon news article ^[10].

3: Revlimid, Velcade, Dexamethasone Combination Produces High Response Rates

In third place is a study that evaluated initial therapy with a combination of Revlimid, Velcade, and dexamethasone in newly diagnosed myeloma patients. The results showed that 100 percent of participants responded to the combination, with 74 percent of participants achieving at least a very good partial response in the Phase 2 part of the trial. The study also demonstrated that the combination was equally effective in patients who underwent autologous stem cell transplantation and patients who did not undergo transplantation.

One of the most important implications of the study was that it showed “safe and effective combination of the two most active classes of novel drugs (immunomodulatory drugs and proteasome inhibitors) with lower-dose dexamethasone,” said Dr. Paul Richardson, from the Dana-Farber Cancer Institute and lead author of the study.

Dr. Richardson also reported an update on the study since publication: “[There has been] continued clinical benefit apparent with or without stem cell transplantation, and reversibility of peripheral neuropathy [has been] seen. [There have been] no second primary [cancers] reported so far with early follow-up, and this combination allows a ‘chemo-sparing’ approach.”

For more information, see the journal Blood ^[11] and the related Beacon news article ^[12].

Runner-Up Journal Articles

Low-Dose Dexamethasone Reduces Toxicity

The first runner-up is a study that compared Revlimid plus high-dose dexamethasone with Revlimid plus low-dose dexamethasone in newly diagnosed myeloma patients. Researchers found that treatment with low-dose dexamethasone resulted in fewer side effects and superior short-term overall survival. The trial was stopped early after just one year because the results were so convincing.

For more information, see the journal The Lancet ^[13] (abstract) and the related Beacon news article ^[14].

Once-Weekly Velcade Reduces Neuropathy

Another important study showed that once-weekly dosing of Velcade in elderly myeloma patients was as effective but better tolerated as compared to the previously standard twice-a-week dosing. Once-weekly Velcade reduced the occurrence of peripheral neuropathy, a side effect characterized by pain and tingling in the hands, arms, legs, and feet.

For more information, see the journal Blood ^[15] and the related Beacon news article ^[16].

VTP Is Equally As Effective As VMP In Elderly Patients

Another important study compared the combination regimen of Velcade, thalidomide, and prednisone ^[17] (abbreviated as VTP) with the standard combination of Velcade, melphalan ^[18] (Alkeran), and prednisone (abbreviated as VMP) in elderly patients. Researchers concluded that VTP and VMP were equally effective. Additionally, the findings indicated that weekly administration of Velcade significantly reduced the rate of peripheral neuropathy.

For more information, see the journal The Lancet ^[19] (abstract) and the related Beacon news article ^[20].

Addition Of Thalidomide To VMP Improves Response Rates In Elderly Patients

Another important study compared the standard combination of VMP with VMP plus thalidomide followed by maintenance therapy with Velcade and thalidomide in elderly myeloma patients.  The results showed that patients treated with the thalidomide regimen achieved better responses.

The study “provides evidence for Velcade-based maintenance in transplant-ineligible patients, which is practice-changing,” said Dr. Usmani, who was not involved with the study.

For more information, see the Journal of Clinical Oncology ^[21] (abstract) and the related Beacon news article ^[22].

Velcade-Dexamethasone Increases Survival In Newly Diagnosed Myeloma Patients

The final runner-up study compared treatment with Velcade plus dexamethasone to treatment with vincristine ^[23], doxorubicin ^[24] (Adriamycin), and dexamethasone in newly diagnosed myeloma patients.  The results showed that patients who received Velcade plus dexamethasone responded better both before and after stem cell transplantation.

The study “is a landmark article demonstrating for the first time that the type of induction therapy, specifically with novel drugs, makes a difference in outcomes for patients undergoing autologous stem cell transplantation,” wrote Dr. Bensinger, who was not involved with the study.

For more information, see the Journal of Clinical Oncology ^[25] (abstract) and the related Beacon news article ^[26].

Conference Abstracts

1: Revlimid Maintenance Therapy After Stem Cell Transplantation Increases Time-To-Disease Progression

According to the physicians surveyed, the most important cutting-edge study presented at a 2010 conference is one that evaluated long-term Revlimid maintenance therapy after stem cell transplantation. Presented at the American Society of Hematology (ASH) meeting, the study demonstrated that Revlimid maintenance therapy nearly doubled progression-free survival (42 months versus 24 months).

Although Revlimid maintenance therapy was reported to be well tolerated, patients receiving Revlimid were more likely to have low white blood cell counts.  A higher rate of patients receiving Revlimid maintenance also reported developing a second cancer, a concern that is being further investigated.

Dr. Vincent Rajkumar from the Mayo Clinic, who was not involved with the study, said that this study is important because it “showed the potential value of maintenance [therapy].”

For more information, please see ASH abstract 310 ^[27] and the related Beacon news article ^[28].

2: Subcutaneous Administration Of Velcade Reduces Side Effects

For second place, the surveyed physicians chose a Phase 3 trial presented at the ASH meeting that investigated the administration of Velcade through subcutaneous injections. Velcade is currently approved in the United States as an intravenous (IV) injection. The findings showed that the subcutaneous injections were just as effective but better tolerated than the IV injections.  In particular, the rate of peripheral neuropathy was significantly reduced when Velcade was administered subcutaneously.

For more information, please see ASH abstract 312 ^[29] and the related Beacon news article ^[30].

3: Carfilzomib Is Well Tolerated And Highly Active Myeloma Therapy

In third place, another ASH conference study investigated the safety and efficacy of carfilzomib ^[31] in patients with relapsed and/or refractory (resistant) myeloma. The results showed a response rate of 24 percent overall and 19 percent for patients who were refractory to Velcade in their last line of treatment.

According to Dr. Ravi Vij, an associate professor of medicine at Washington University in St. Louis and one of the investigators, the study is significant because it demonstrated that carfilzomib is effective in patients who had previously not responded to Velcade or Revlimid. He predicts that the U.S. Food and Drug Administration may approve carfilzomib as a new myeloma drug later this year.

For more information, please see ASH abstract 985 ^[32] and the related Beacon news article ^[33].

Runner-Up Conference Abstracts

Revlimid Maintenance After Stem Cell Transplantation Is Highly Effective

The first runner-up is another study presented at the ASH meeting that evaluated the efficacy and safety of Revlimid as a maintenance therapy after stem cell transplantation. Patients treated with Revlimid maintenance had a superior time-to-disease progression compared to patients who did not undergo maintenance therapy (42 months versus 22 months). However, more patients who received Revlimid experienced side effects, most notably low blood cell counts, bacterial infections, and the development of second cancers.

For more information, see ASH abstract 37 ^[34] and the related Beacon news article ^[28].

Elotuzumab Combination Is Effective And Well Tolerated In Relapsed/Refractory Myeloma

Another important study presented at ASH investigated elotuzumab ^[35] in combination with Revlimid and low-dose dexamethasone in relapsed and refractory myeloma patients. The response rate was 82 percent overall and 96 percent for patients who had not been previously treated with Revlimid. The most common side effects were low white blood cell counts and low platelet counts.

For more information, see ASH abstract 1936 ^[36] and the related Beacon news article ^[37].

Revlimid Maintenance Improves Response Rates In Newly Diagnosed, Elderly Patients

Another important study presented at ASH evaluated the addition of Revlimid to melphalan and prednisone in elderly patients with newly diagnosed myeloma. Researchers found that patients treated with the combination regimen, followed by Revlimid maintenance therapy, experienced rapid and improved response rates.  Similar to the other two Revlimid maintenance studies presented at ASH, Revlimid maintenance doubled time-to-disease progression (31 months versus 13 months).  Also similar to the other two studies, patients receiving maintenance therapy were more likely to develop low white blood cell counts and second cancers.

For more information, see ASH abstract 622 ^[38] and the related Beacon news article ^[28].

Pomalidomide Is Effective And Safe In Relapsed Myeloma

Another important study presented at the ASH meeting found pomalidomide ^[39] (Actimid) to be effective and safe in relapsed myeloma patients who were resistant to Revlimid and Velcade.  The maximum tolerated dose of pomalidomide was 4 mg, and the main side effect was low blood cell counts.  When treated with pomalidomide alone or in combination with dexamethasone, 25 percent of participants responded.

For more information, see ASH abstract 864 ^[40] and the related Beacon news article ^[41].

Velcade-Containing PAD Is More Effective Than VAD

The final runner-up is another study presented at ASH.  The study evaluated initial therapy with Velcade, doxorubicin, and dexamethasone (known as PAD), compared with the previous standard initial therapy of vincristine, doxorubicin, and dexamethasone (known as VAD). Following stem cell transplantation, patients who received PAD initial therapy then received Velcade maintenance therapy, and the other study participants received thalidomide maintenance therapy.

The researchers found that overall survival for patients receiving the Velcade regimen was 78 percent, compared to 71 percent for those treated with VAD and thalidomide maintenance.  Additionally, response rates and progression-free survival were superior in the Velcade group.

For more information, see ASH abstract 40 ^[42] and the related Beacon news article ^[43].

The Myeloma Beacon would like to thank the physicians who participated in the survey for their assistance and expertise:

William I. Bensinger, M.D. ^[44]
Fred Hutchinson Cancer Research Center, Seattle, WA

James Berenson, M.D. ^[45]
Berenson Oncology, West Hollywood, CA

Sergio A. Giralt, M.D. ^[46]
Memorial Sloan-Kettering Cancer Center, New York City, NY

C. Ola Landgren, M.D., Ph.D. ^[47]
National Cancer Institute and National Institutes of Health, Bethesda, MD

S. Vincent Rajkumar, M.D. ^[48]
Mayo Clinic, Rochester, MN

Paul G. Richardson, M.D. ^[49]
Dana-Farber Cancer Institute, Boston, MA

David S. Siegel, M.D., Ph.D. ^[50]
John Theurer Cancer Center, Hackensack, NJ

Saad Zafar Usmani, M.D., FACP ^[51]
University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy, Little Rock, AR

Ravi Vij, M.D. ^[52]
Washington University in Saint Louis, MO

Hermann Einsele, M.D.
University of Wurzburg, Germany

Antonio Palumbo, M.D.
University of Torino, Italy

Jesus F. San Miguel, M.D.
University of Salamanca, Spain