Highlights of the 11th International Myeloma Workshop in Kos, June 25th until June 29th, 2007

The following report on the International Myeloma Workshop in Kos, was written by Greetje Goossens, a myeloma patient herself and one of the European Myeloma Platform counsellors. She attended the workshop together with 3 other members of EMP. She looks at the information obtained at this workshop from a patients’ perspective.

Myeloma experts from all over the world come together every 2 years at the International Myeloma Workshop (IMW). This year the 11th IMW took place on the sunny isle of Kos in Greece.

The latest research results and the most recent developments in the field of MM are shared among the specialists during the IMW.

Being a MM patient myself, it touched me very much to see the commitment, the motivation and the worldwide collaboration between those myeloma specialists, who are persistently working very hard to come closer to a cure for our disease. In the light of the new therapies presented at this workshop, we can start to consider multiple myeloma in many cases as a chronic disease. Next step could be that we finally head towards a cure in the next decade.

The general message of the workshop was one of hope. Hope because a lot of progress has been made in recent years. Many novel agents offer new treatment options, as well for newly diagnosed as for previously treated patients. Hope because much longer survival times have been reported in studies with those novel agents, more specifically in treatments where they are combined.

One of the big news items is that there are now more steroid-free (or steroid-low) options being trailed and used with some of the novel agents. Among those novel agents are bortezomib (Velcade) and the IMiD’s (Immunomodulatory drugs): thalidomide and lenalidomide (Revlimid). With these new medicines we do not have to rely completely on high-dose steroids and chemotherapy.

The front-line treatment of the newly diagnosed patient is changing due to the introduction of these new agents. . Treatments successfully given to the patient in the refractory and relapsed phase are now also moving forward to the newly diagnosed patient. But previously treated patients with relapsed or refractory MM can also benefit from the new therapies, as was presented at this workshop.

Exciting study-results were given about the use of these novel medicines in combination therapy either with some traditional drugs or with other new agents.

Some examples of studies with the combination therapy:

1. Induction treatment:

1.1. The elderly patient (non-transplant candidates):

* combinations with MP (melphalan and prednisone)

Results were presented from the IFM 01-01 trial (from the InterGroupe Francophone du Myélome), which compared the melphalan, prednisone and thalidomide (MPT) treatment regimen with melphalan and prednisone (MP) alone in previously untreated patients of age 75 and older. The results were very encouraging when thalidomide was added to the standard MP combination: the MPT regimen showed major benefits in response rates, time to progression and overall survival and with an acceptable toxicity profile. Therefore, this new combination can be offered to elderly patients with myeloma.

Furthermore, Dr. Palumbo looked at the combination of lenalidomide (Revlimid) with MP, the so-called MPR regimen. High complete and near complete remission rates were obtained with the MPR regimen. The responses looked as good, possibly even better than the MPT experience with the additional advantage that there was less neuropathy associated with the MPR combination.

A phase III study comparing the MP versus MPV (MP plus bortezomib/Velcade) regimen. The first analyses are expected by the end of August 2007 but this trial will most likely confirm the superiority of adding bortezomib to MP. So, here we will have another successful regimen for treating older patients with myeloma who are not eligible for high-dose therapy.

* lenalidomide (Revlimid) and bortezomib (Velcade) based combinations:

The effectiveness of the therapy with Revlimid + dexamethasone for relapsed and refractory MM is in the meantime well documented. It is for this indication that EMEA granted a marketing authorisation for Revlimid in June 2007.

But brand new data were given about the first-line therapy with lenalidomide and dexamethasone where the reduction of the dose dexamethasone proved to be very efficient. The combination lenalidomide with low-dose dexamethasone was over the whole line more efficient and much better tolerated than the regimen where high-dose dexamethasone was added. Also, 1-year survival rates were superior in the low-dose regimen.

These results show us that for treatment with those novel agents, one should not systematically aim at the highest possible doses, but rather look for a balance between effectiveness and tolerance of the medicine.

1.2. Transplant candidates:

If we look at patients who are transplant candidates, there is enough evidence to say that chemotherapy alone might not be the optimal induction approach (Dr. Dimopoulos). The lenalidomide/dexamethasone regimen would be appropriate for induction treatment, and thus be appropriate as a standard care for the patient who is a candidate for stem cell collection. The combination bortezomib/dexamethasone also seems to be very efficient in this context. When compared with the traditional VAD induction therapy, the CR-rate was doubled with the bortezomib/dexamethasone therapy and this resulted also in higher remission rates after autologous stem-cell transplantation. Dr. Morgan presented promising results about a combination therapy of bortezomib with Cyclophosphamide and a steroid

So, some of those novel agents not only enhance the pre-transplant but also the post-transplant response.

2. The relapsed/refractory patient:

The data of Dr. Orlowski about a combination of bortezomib and Doxil (a special preparation of doxorubicin) not only show better remission results than the administration of bortezomib alone, it also increases the progression free survival time. Interesting this is a cortisone-free combination.

The combination of bortezomib and lenalidomide has also shown a high response rate in relapsed and refractory MM patients and data show that these novel agents have the capacity to overcome the impact of unfavourable cytogenetics (chromosomal abnormalities such as mutations or deletions e.g. 13q deletion) on the course of the disease. For the first time effective treatment is offered to patients who otherwise respond poorly to traditional therapies. Dr. Richardson treated also a small group of newly diagnosed patients with a three-drug combination, using lenalidomide, bortezomib – two most powerful recently approved drugs – and dexamethasone. Up to now, the data of these interesting trial look quite successful with every patient responding, either with a complete response or with a very good partial remission. Moreover, this combination appears to be very well tolerated especially when using a lower dose of dexamethason. However, more patients need to be treated with this encouraging regimen to confirm the results.

In addition, some of the combinations of the novel agents bring hope for relapsed patients who even had some resistance to the drugs early on in their journey with MM. Many of those patients are now able to use the medicines again in combination therapy where the resistance against the individual drug can be reversed.

Without going further into detail, new forward-looking perspectives in the treatment of MM can also be found in therapy with “heat shock protein inhibitors”, especially in combination with bortezomib.

Also a new generation of proteasome inhibitors (with less toxicity when compared to the previous generation) is seeing the light of the day, which offer again some perspectives in case of bortezomib resistance.

As a result we can say that the combination therapies with those novel agents hold great promise for future treatments and that the results obtained from the studies with those agents can compete with results that, up to now, only high-dose chemotherapy could bring us.

Consequently, at the workshop the debate was opened on how important it is to undergo appropriate therapy to try to achieve a CR. This still implies for many patients a stem cell transplant, but with those novel agents at the treatment horizon.

The results with some of these novel combinations are so promising that many experts are thinking that a particular combination could give equal or even better results than those obtained with stem cell transplantation and a more traditional induction treatment.

The arrival of the novel therapies will have a great impact on the future treatments of MM patients. At the 11th IMW in Kos, we were witnessing what is truly a paradigm shift in treatment for the multiple myeloma patients.

In the decennia behind us, the horizon for the MM-patient was packed with dark and grim clouds. Now this horizon definitely starts to brighten up thanks to the excellent work of the dedicated and tenacious myeloma experts.

I think I can speak in name of all multiple myeloma patients when I say that I would like to thank all of them from the bottom of my heart. Keep up the good work!