Yesterday was the second day of the International Myeloma Workshop (IMW) in Paris.  The day was full of presentations from early morning through the evening, and the day concluded with a poster session.

Some of the highlights from Day 2 of the conference are summarized in this article.  For more detailed summaries of the day's sessions, see The Beacon’s extensive Day 2 coverage in the Beacon Forums.

Treating Younger, Newly Diagnosed Myeloma Patients

The first session of the morning was about treating newly diagnosed patients under the age of 65 years.

First, Dr. Michele Cavo from the University of Bologna in Italy spoke about the key questions related to the treatment of these patients: What is the best induction therapy prior to stem cell transplant?  What is the best consolidation therapy?  What kind of maintenance therapy – if any – is best?

To address the current understanding on these topics, Dr. Cavo presented results from a number of studies.

Regarding induction therapy, studies have indicated that a combination of Velcade (bortezomib), dexamethasone (Decadron), plus one or two other agents is likely to achieve the highest response rate.  (Several speakers later in the session, however, noted that there also is increasing support for the use of a combination of Revlimid (lenalidomide), Velcade, and dexamethasone as induction therapy.)

The data are less conclusive as to what consolidation regimen is optimal.  However, there are good data supporting Velcade, thalidomide (Thalomid), plus dexamethasone.

For maintenance therapy, several ongoing studies are showing that Revlimid maintenance has a significant benefit.

Throughout the rest of the session, speakers from a variety of different countries discussed what researchers in their countries see as key issues related to the treatment of younger, newly diagnosed myeloma patients, and the trials that are planned -- or which have started recently -- to shed light on the key open questions related to the treatment of this patient group.

The speakers expressed ongoing concern over the best way to use stem cell transplants:  Are transplants necessary given the efficacy of the new myeloma treatments?  What is the best timing?  Should patients receive one or two?  These important questions are being addressed in a number of the new or recently started studies.

Another common concern discussed during the session is the need to personalize treatment, which generally means tailoring treatment based on whether a patient is low-risk or high-risk (see related Beacon news written by Dr. Vincent Rajkumar of the Mayo Clinic).  Most of the ongoing clinical trials described during the session use several methods to fully categorize all participants, so that detailed analyses can be conducted on which types of patients respond best to the treatment regimens in the trial.

Finally, Dr. Bart Barlogie from the University of Arkansas for Medical Science urged his colleagues to use imaging methods when determining whether a patient has truly achieved a complete response.  He said that even patients who achieve a complete response can have myeloma cells in lesions within their bones.  He recommended these patients should continue to be treated with the goal of killing off all remaining myeloma cells in the lesions.

The Continuum Of Care For Myeloma Patients

The second session of the day was sponsored by Celgene, the company that markets thalidomide and Revlimid.

Dr. Sergio Giralt from Memorial Sloan Kettering in New York discussed the evidence supporting continuing therapy after induction therapy.

He explained that longer therapy can help eliminate myeloma cells that survive initial therapy.  This keeps patients in remission longer, which in turn can minimize damage to a patient’s organs.

Of course, longer therapy also increases the risk and duration of side effects.  It is also possible that any myeloma cells that continue to survive may do so because of mutations that make them more resistant to future treatment.  Longer therapy also means higher costs to the patient and health care system.

Despite the potential drawbacks, Dr. Giralt believes additional therapy is beneficial.

The final talk during this session was given by Dr. Kenneth Anderson of the Dana-Farber Cancer Institute in Boston.  He spoke mainly about new treatments under development for myeloma.

He discussed elotuzumab, saying it is likely to be used in combination with Revlimid and dexamethasone. He also mentioned perifosine, which will probably be used in combination with Velcade. Similarly, panobinostat and Zolinza (vorinostat) are likely to be used in combination with Velcade or carfilzomib (if the latter is approved by the Food and Drug Administration).

Carfilzomib and pomalidomide, on the other hand, appear to be sufficiently active against myeloma that they may be used on their own (in combination with dexamethasone) or together with one of the novel agents and dexamethasone.

Dr. Anderson had also spoken about these agents during an interview with The Myeloma Beacon (see related Beacon news).

High-Risk Multiple Myeloma

The afternoon started with a session focused on the biology and treatment of high-risk myeloma.

During the first presentation, Dr. Leif Bergsagel from the Mayo Clinic in Arizona spoke at length about the chromosomal abnormality t(4;14), in which a region of chromosome 4 is translocated to chromosome 14.  This abnormality has been believed to be associated with poor survival.  During his presentation, Dr. Bergsagel also discussed some intriguing laboratory results showing that the treatment of myeloma with lower-than-optimal drug doses can lead to more rapid recurrence of the disease and shorter survival times.

In a later presentation during the session, Dr. Morgan from the Royal Marsden Hospital in the United Kingdom also discussed the t(4;14) abnormality.  His research findings indicate, however, that the abnormality may not be as negative for a patient’s prognosis as was previously thought.  Instead, it appears that t(4;14) patients often have a poor prognosis because they usually have additional chromosomal abnormalities.

Dr. Keith Stewart, also from the Mayo Clinic in Arizona, spoke about his approach to treating high-risk patients.  He believes it is best to treat high-risk patients with a combination of drugs.  However, since high-risk patients are likely to have relatively unstable DNA, Dr. Stewart does not recommend treating them with DNA-damaging drugs, such as melphalan (Alkeran) or cyclophosphamide (Cytoxan).

During Dr. Bart Barlogie’s presentation, he stated that he believes low-risk patients eventually develop characteristics similar to those of high-risk patients.  This is why Dr. Barlogie feels it is so important to better understand how to treat high-risk patients.

In the last presentation of the session, Dr. Herman Einsele of the University Hospital of Würzburg, Germany, discussed the role of allogeneic (donor) stem cell transplants for high-risk patients.  Although these transplants can be curative, the evidence is conflicting as to whether donor transplants are beneficial.  Several trials support the use of donor transplants for high-risk patients.  Additionally, the risks associated with donor transplants have declined as researchers have learned how to deal with these risks.  Therefore, Dr. Einsele believes donor transplants should be considered as an option for high-risk patients.

Debate Whether Smoldering Myeloma Patients Should Be Treated

The next session was a debate between Dr. María-Victoria Mateos of the University Hospital of Salamanca, Spain, and Dr. Sagar Lonial of Emory University in Atlanta.  The debate was about whether to treat some or all patients with smoldering myeloma.

Dr. Mateos is of the opinion that some smoldering myeloma patients should be treated.  Dr. Lonial, however, believes that physicians should be hesitant to treat smoldering patients, even those that are high-risk for progressing to active myeloma.

In an ongoing Spanish trial, half of the high-risk smoldering patients in the trial are being treated with an initial round of Revlimid and dexamethasone followed by Revlimid maintenance.  The other half are not being treated.

Dr. Mateos reported that so far, 10 percent of the patients receiving treatment have progressed, compared to 46 percent of patients who are not being treated.  The latest data also show Revlimid treatment significantly extends survival.

Dr. Lonial’s argument is that smoldering myeloma patients, who have no symptoms from their disease, will experience side effects if treated and many will feel much worse than they would have without treatment.  He is not completely convinced that the small survival benefit seen thus far in Dr. Mateos’ trial is worth the decline in quality of life experienced by the treated patients.

To further test the benefits of treatment, Dr. Lonial is conducting a study in which medium- and high-risk smoldering patients are being treated with Revlimid (without dexamethasone, which has many undesirable side effects).  The trial is carefully tracking measures of quality of life.

From the discussion that followed, the Spanish data certainly made much of the audience receptive to treating certain smoldering patients, but it was not clear that treatment practices would change yet.

As mentioned earlier, detailed summaries of the day's sessions are available in The Beacon’s Day 2 coverage in the Beacon Forums.  For links to abstracts of some of the presentations given during the day, see the IMW programme.  The Myeloma Beacon will be publishing regular “as it happens” updates from Day 3 and Day 4 of the IMW in the Beacon's multiple myeloma forums.  News from each day will also be summarized in daily updates like this one.