The year 2009 brought a lot of new and ex­cit­ing ad­vancements in the field of mul­ti­ple myeloma. Over the course of 2009, The Myeloma Beacon covered more than 100 im­por­tant myeloma-related stud­ies ^[1].

To highlight the most im­por­tant of these stud­ies, the Myeloma Beacon surveyed lead­ing physicians and re­searchers in the field. These physicians and re­searchers were asked to name the three peer reviewed journal articles pub­lished in 2009 and the three conference abstracts from 2009 that have the most im­por­tant findings or implications relating to mul­ti­ple myeloma.

The top three journal articles and conference abstracts that they chose are pre­sented below.

Journal Articles

1: Poma­lido­mide Shows Remarkable Activity In Myeloma

According to the physicians surveyed, the most im­por­tant study pub­lished in 2009 eval­u­ated a com­bi­na­tion of pomalidomide ^[2] (Actimid, CC-4047) and low-dose dexamethasone ^[3] (Decadron) in re­lapsed and re­frac­tory myeloma patients. In the study, 63 per­cent of patients, many of whom had been resistant to thalidomide ^[4] (Thalomid), Revlimid ^[5] (lena­lido­mide), and Velcade ^[6] (bor­tez­o­mib), responded favorably to the treat­ment.

The study con­firmed earlier re­­sults in­di­cating that poma­lido­mide is the most potent drug of its kind, a class of mol­e­cules, known as immuno­modu­la­tory agents, that in­cludes thalido­mide and Revlimid.

For more in­for­ma­tion, please see the Journal of Clinical Oncology ^[7] (abstract) and the re­lated Beacon news ^[8] article.

2: MGUS Always Precedes Multiple Myeloma

In sec­ond place, a pro­spec­tive study analyzed the blood samples taken from myeloma patients before their diag­nosis. Re­searchers learned that in nearly every case, the patients had mono­clonal gam­mop­athy of undetermined sig­nif­i­cance (MGUS), a blood disorder present in three per­cent of Americans over the age of 50.

According to Dr. S. Vincent Rajkumar, a pro­fessor of med­i­cine at the Rochester, Minnesota, Mayo Clinic and an author on the paper, the study’s findings settle a long-standing debate on whether MGUS is a con­sis­tent predecessor to myeloma. Re­searchers can now focus on identifying factors that in­crease the risk of MGUS pro­gres­sion.

“By studying mech­a­nisms that are asso­ci­ated with pro­gres­sion, we will [ultimately] be able to de­vel­op earlier ther­a­pies that can be used to delay or prevent myeloma from hap­pen­ing,” wrote Dr. Ola Landgren, an in­ves­ti­ga­tor at the National Cancer In­sti­tute and lead author of the study, in an email to the Beacon.

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

3: Maintenance Therapy After Transplantation Prolongs Life Expectancy

In a tie for third place is a study eval­u­ating the post-transplantation ben­e­fits of either prednisone ^[11] or a com­bi­na­tion of pred­ni­sone and thalido­mide, for patients treated with thalido­mide and an au­tol­o­gous stem cell trans­plant. Patients in the com­bi­na­tion ther­apy group ex­peri­enced a longer remission duration and over­all sur­vival.

For more in­for­ma­tion, see the Journal of Clinical Oncology ^[12] (abstract) and the re­lated Beacon news ^[13] article.

3: Very Good Partial Re­sponse Is A Good Indicator of Long-Term Outcome

The other third place study examined how patient re­sponse to treat­ment was asso­ci­ated with event-free and over­all sur­vival. Re­searchers followed up with patients who had undergone an au­tol­o­gous stem cell trans­plant for a median of 67 months. They discovered that patients who achieved very good partial re­sponse or better had sig­nif­i­cantly longer event-free and over­all sur­vival.

Based on their re­­sults, re­searchers rec­om­mended that very good partial re­sponse should be­come the standard treat­ment goal for patients since it is more attainable than com­plete re­sponse, yet offers similar ben­e­fits in event-free and over­all sur­vival.

For more in­for­ma­tion, see the Journal of Clinical Oncology ^[14] (abstract) and the re­lated Beacon news ^[15] article.

Conference Abstracts

1: Velcade Treatment Options In Elderly Patients With Newly Diagnosed Myeloma

The surveyed physicians voted as most im­por­tant a study pre­sented at the American Society of He­ma­tol­ogy (ASH) conference in early De­cem­ber in which re­searchers com­pared an induction ther­apy com­bi­na­tion of Velcade, thalido­mide and pred­ni­sone (VTP) with the already-popular regi­men of Velcade, melphalan ^[16] (Alkeran), and pred­ni­sone (VMP) in newly diag­nosed elderly patients. Both treat­ments proved to be equally and highly ef­fec­tive.

Researchers also com­pared main­te­nance ther­a­pies of Velcade-thalidomide (VT) and Velcade-prednisone (VP), both of which im­proved patient re­spon­siveness to the point of overcoming neg­a­tive ge­netic risk factors.

For more in­for­ma­tion, please see ASH abstract 3 ^[17] and the corresponding Beacon news ^[18] article.

2: Revlimid Treatment Options In Elderly Patients With Newly Diagnosed Myeloma

For sec­ond place, the surveyed physicians chose a Phase 3 trial pre­sented at the ASH conference that in­ves­ti­gated Revlimid’s ef­fec­tiveness as both an induction and main­te­nance ther­apy. Patients treated with a com­bi­na­tion of mel­phalan, pred­ni­sone, and Revlimid followed by Revlimid main­te­nance had a de­creased risk of dis­ease pro­gres­sion than patients treated with mel­phalan and pred­ni­sone followed by a placebo.

Final re­­sults of the study are ex­pected at the American Society of Clinical Oncology meeting later this year. The study’s findings offer sub­stan­tial sup­port for Celgene as it applies for FDA ap­prov­al of Revlimid as a first-line treat­ment op­tion in mul­ti­ple myeloma.

For more in­for­ma­tion, please see ASH abstract 613 ^[19] and the corresponding Beacon news ^[20] article.

3: VMPT Effectively Treats Elderly Patients With Newly-Diagnosed Myeloma

In a tie for third place, another ASH conference study in­ves­ti­gated the im­pact of adding thalido­mide to the standard regi­men of Velcade, mel­phalan, and pred­ni­sone (VMP). Patients treated with VMPT had a greater re­sponse rate than those treated with VMP, but they also encountered more blood-related side effects.

“VMPT rep­re­sents the next gen­er­a­tion,” wrote Dr. Antonio Palumbo, chief of the myeloma unit at the Uni­ver­sity of Torino in Italy and lead author of the study, in an email to the Beacon. “[The four drugs] im­prove re­sponse and pro­gres­sion-free sur­vival with a higher toxicity, but this is [still] the first schema that is superior to VMP.”

For more in­for­ma­tion, please see ASH abstract 128 ^[21] and the corresponding Beacon news ^[22] article.

3: Elotuzumab Com­bi­na­tion Produces Encouraging Results In Multiple Myeloma

Also tied for third place is another ASH pre­sen­ta­tion that provided pos­i­tive re­­sults about the ef­fec­tiveness of elotuzumab ^[23] in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone at treating mul­ti­ple myeloma. The com­bi­na­tion ther­apy led to a 92 per­cent re­sponse rate from patients, with man­ageable side effects.

A new anti­body, elotuzumab targets pro­teins that are unique to myeloma cells and causes the cells to die.

“This is an im­por­tant study because it rep­re­sents the first evi­dence that an anti­body can have ef­fi­cacy in myeloma, and it con­firms the sug­gestion that Revlimid en­hances immunity and thus en­hances the ef­fi­cacy of an im­mune-mediated agent like elotuzomab,” wrote Dr. Sagar Lonial, an asso­ci­ate pro­fessor at Emory Uni­ver­sity’s School of Medicine and lead author of this study, in an email to the Beacon.

A multinational con­tin­u­a­tion of the trial is cur­rently recruiting patients. For more in­for­ma­tion, please see the clinical trial ^[24] description, ASH abstract 432 ^[25], and the corresponding Beacon news ^[26] article.

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

S. Vincent Rajkumar, M.D.
Mayo Clinic, Rochester, MN

Sundar Jagannath, M.D. ^[27]
St. Vincent’s Comprehensive Cancer Center, New York, NY

Sagar Lonial, M.D. ^[28]
Winship Cancer In­sti­tute
Emory Uni­ver­sity School of Medicine, Atlanta, GA

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

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