Myeloma researchers and physicians gathered at the 2011 International Myeloma Workshop (IMW) earlier this month to discuss the current under­standing of the biology and treatment of multiple myeloma.

Highlights from each day of the workshop were covered in the Beacon’s daily updates from the meeting.

Now that the IMW has ended, however, and there has been some time to digest all that happened, it seems like a good time to ask: What were the key themes and learnings from the conference?

To answer this question, The Beacon went back and reviewed its coverage of the IMW, and it also spoke with several myeloma specialists to get their perspective on the conference.

Revlimid Maintenance Therapy

Most of the myeloma specialists the Beacon spoke with felt that the latest results regarding Revlimid (lenalidomide) maintenance therapy were a key topic covered at the IMW.  Opinions differed, though, on what the results may mean for myeloma patients.

Preliminary results presented last December showed that, in each of three major Revlimid maintenance studies, a higher percentage of patients receiving Revlimid maintenance therapy developed a second cancer compared to patients who did not receive maintenance therapy.

Updated results presented at the IMW confirmed an increased rate of second cancers in the Revlimid groups.

“From a clinical viewpoint, the number one development [at the IMW] was the first full report of second primary cancers with Revlimid maintenance, which appears to be an ever increasing problem, already 8 percent with a median follow-up of only two years,” said Dr. Leif Bergsagel from the Mayo Clinic in Arizona.

Many physicians, however, are not yet convinced that second cancers are an issue when it comes to Revlimid maintenance therapy.  Dr. Edward Libby from the University of New Mexico, for example, told the Beacon “The information available to date is based on very small patient numbers, and the cancers are a broad range of malignancies.  No clear pattern of secondary cancers has emerged.”

In regard to the efficacy of Revlimid maintenance, previous results from each of the trials showed that Revlimid doubled progression-free survival.  However, with data showing an increased risk of second cancers, it had been unclear whether the benefits of Revlimid maintenance outweighed the risks.

At the IMW, Dr. Philip McCarthy from the Roswell Park Cancer Center presented updated results from the CALGB study that clearly demonstrated a survival benefit to Revlimid maintenance therapy after stem cell transplantation, regardless of any increased risk of secondary cancers.

For most of the panel members at the IMW session on Revlimid maintenance therapy, these and other related results were enough to convince them that the benefits from Revlimid maintenance therapy outweigh the risks.

Once again, though, there are myeloma researchers who see things a bit differently.

“The question everyone is asking themselves is: Is the risk worth the benefit?” said Dr. Sergio Giralt from Memorial Sloan-Kettering Cancer Center in a discussion with The Beacon.  “I don’t think that the data presented were definitive in the sense that everybody should be doing [Revlimid] maintenance.”

To clarify, Dr. Giralt added, “For patients who now are four months post-transplant and still have evidence of disease from not achieving a complete remission, the threshold or bar to start these patients on some form of post-transplant maintenance is actually much lower than what it was."

“On the other hand, if you have a patient with low-risk disease and he is in complete remission, the bar to start that patient on [Revlimid] probably got a little bit higher.  Because that patient is going to ask the question, ‘Should I expose myself to this?’” Dr. Giralt explained.

The Heterogeneity Of Myeloma

A number of the myeloma specialists the Beacon spoke with also mentioned that the IMW reinforced the realization that myeloma is a very varied, or "heterogeneous," disease.

In particular, there was considerable discussion about the challenge presented by high-risk myeloma and the need for aggressive, personalized treatments for high-risk patients based on their disease characteristics.

Dr. Bart Barlogie from the University of Arkansas for Medical Sciences highlighted the meeting’s “emphasis on high-risk myeloma occurring in 15 percent of newly diagnosed patients and representing an inevitable pathway in final disease stages.”

Despite the broad-based recognition of the heterogeneity of myeloma, there continue to be different approaches to treating patients based on their disease risk.

For instance, Dr. Barlogie told The Beacon, “The total therapy concept – whether implemented in the Arkansas way with tandem transplants plus all new drugs or with novel agents combined with standard cytogenetics [chromosomal abnormalities] – is key to address the early suppression of myeloma subclone evolution.”

Dr. Bergsagel stated, “From a biologic standpoint, the number one development was the recognition of the high degree of tumor heterogeneity and genomic instability in high-risk multiple myeloma, which argues for the use of three-drug combination therapy for these patients.”

“Conversely, the relative homogeneity and genomic stability of standard risk multiple myeloma supports the use of less toxic two-drug regimens in this patient population,” he said.

Dr. Hermann Einsele from the University of Würzburg in Germany was encouraged by the first report that very high-risk myeloma patients may benefit from allogeneic (donor) stem cell transplants, a procedure that has been controversial due to the high risk of life threatening complications.

Heterogeneous disease was not only discussed in the context of multiple myeloma but also in regard to smoldering myeloma, the stage in myeloma's development when the disease's symptoms are not yet present.

“From my point of view, one of the most important developments presented at the IMW in Paris was that we probably will be able to offer in the near future an early treatment for [smoldering] myeloma patients at high-risk of progression to active disease,” said Dr. María-Victoria Mateos of the University Hospital of Salamanca in Spain.

“The Spanish Myeloma Group presented that early treatment with [Revlimid] plus dexamethasone [Decadron] followed by [Revlimid] as maintenance therapy is significantly superior to no treatment,” Dr. Mateos told The Beacon in regard to these high-risk smoldering myeloma patients.  “The most important finding is the benefit observed in time to progression to active disease, and in fact, the group has just started to observe a benefit in terms of overall survival.”

Advances In Tools

With greater emphasis on heterogeneity of disease, myeloma specialists also are recognizing a greater need for advanced tools and methods to determine disease type and monitor the extent of response to treatment.

At the IMW, this was reflected in frequent discussions of new methods for determining a patient's specific chromosomal abnormalities and disease characteristics.  These methods include gene expression profiling (GEP) and single-nucleotide polymorphism (SNP) arrays, which increasingly are being used to complement the more traditional fluorescence in situ hybridization (FISH) testing many myeloma patients already undergo.  These newer techniques can be used not only at diagnosis but also to monitor how a patient’s disease changes over time.

The first study to use whole genome sequencing to compare variations in the genomes of several myeloma patients was reported just a few months ago and also was discussed at the IMW.  It is not yet clear, however, what implications this research may have for myeloma patients or whether this testing will become more common over time.

It was clear at the meeting, in contrast, that advanced imaging techniques such as whole-body MRI and combined PET/CT scans are being used more commonly in combination with blood tests to help determine the best treatment for patients and assess their response to treatment.

Additional Takeaways

A few of the myeloma specialists the Beacon spoke with also commented on the growing number of promising potential new treatments for myeloma as well as the usefulness of the consensus guidelines that were presented at IMW.

“Speakers presented results about novel proteasome inhibitors (carfilzomib), novel immunomodulator drugs (pomalidomide), histone deacetylase inhibitors (panobinostat, [Zolinza], [Istodax]), and so on,” said Dr. Mateos.  “Although some of the results presented were preliminary, most of them were very attractive and promising, especially because they can be combined with conventional agents to achieve a synergistic effect.”

At the meeting, new consensus recommendations were presented in regard to managing low red blood cell counts, blood clots, and bone disease as well as preventing infection.  Dr. Libby said, “These guidelines help to standardize treatment of myeloma patients all over the world and are a welcome advance.”

For more information about the IMW proceedings, see the Beacon’s Daily Updates from the meeting and the Beacon’s detailed coverage of the meeting in the Beacon forums.

The Beacon’s coverage of this year's International Myeloma Workshop was made possible in part by financial support from the Tackle Cancer Foundation.