On the fourth and final day of the American Society of Hematology (ASH) 2011 annual meeting, there was one session in the morning with a number of important myeloma-related presentations.

The key findings of those presentations are summarized in this article.

Treatment Of High-Risk Smoldering Myeloma

Dr. María-Victoria Mateos from the University Hospital in Salamanca, Spain, kicked off the session.

She gave a presentation reviewing a Phase 3 trial she and her colleagues are conducting on the treatment of high-risk smoldering myeloma patients with Revlimid ^[1] (lenalidomide) and dexamethasone ^[2] (Decadron) (abstract ^[3]).

Dr. Mateos discussed initial results of this trial during a debate with Dr. Sagar Lonial of Emory University that was held at the International Myeloma Workshop earlier this year (see related Beacon ^[4] news and detailed coverage ^[5] of the debate in the Beacon's discussion forum ^[6]).

The trial Dr. Mateos and her colleagues are conducting is comparing two alternative approaches to high-risk smoldering myeloma.

Patients in one arm of the trial are receiving initial treatment with Revlimid and dexamethasone followed by Revlimid as maintenance therapy.

Patients in the other arm are receiving no active treatment (which, currently, is the standard of care).

Thus far, 119 patients with high-risk smoldering myeloma have enrolled in the trial.

Patients in the active treatment arm of the trial receive nine four-week cycles of induction therapy with Revlimid and dexamethasone, followed by Revlimid maintenance until disease progression.

After induction therapy, 86 percent of patients responded to treatment, with 14 percent achieving a stringent complete/complete response, 11 percent a very good partial response, and 61 percent a partial response. After a median of 15 cycles of maintenance therapy, the stringent complete/complete response rate increased to 28 percent.

After a median follow-up of 22 months, 15 percent of patients who received Revlimid-dexamethasone progressed to symptomatic disease, compared to 59 percent of patients who did not receive any active treatment.

The median time to disease progression was 23 months for patients in the no-active-treatment arm; the median has not yet been reached for patients treated with Revlimid.

The estimated three-year overall survival rate is 93 percent for patients who received Revlimid and 76 percent for patients who did not.

Dr. Mateos concluded that the Revlimid treatment regimen significantly prolongs time to progression to symptomatic myeloma, and it also appears to increase survival.  Moreover, it does this without a high risk of serious side effects.

Six-Year Results From The Myeloma IX Trial

The second presentation was given by Dr. Gareth Morgan of the Institute of Cancer Research in London. He reviewed the latest results, based on a six-year follow-up, of the so-called Myeloma IX trial -- the largest multiple myeloma clinical trial ever conducted (abstract ^[7]).

Participants in the Myeloma IX trial were newly diagnosed myeloma patients of all ages.

The trial comprised two broad treatment pathways.

The first was for younger, fitter patients (the "intensive" pathway).  In it were two groups of patients.  One group received upfront treatment with cyclophosphamide ^[8] (Cytoxan), thalidomide ^[9] (Thalomid), and dexamethasone ("CTD").  Another group received upfront treatment with cyclophosphamide, vincristine ^[10] (Oncovin), doxorubicin ^[11] (Adriamycin), and dexamethasone ("CVAD").

Most patients in the intensive pathway went on to receive a stem cell transplant after their upfront treatment regimen.

The second pathway, intended for older, less physically fit patients (the "non-intensive" pathway) also was broken into two patient groups:  one was treated upfront with melphalan ^[12] (Alkeran) and prednisone ^[13] ("MP"), and the other received initial treatment with an attenuated CTD regimen ("CTDa").

All patients in the trial, regardless of pathway, also received either Zometa ^[14] (zoledronic acid) or Bonefos (clodronate) as a treatment for bone disease.

In both pathways, patients were randomized following initial treatment to receive either low-dose thalidomide maintenance treatment or no maintenance treatment whatsoever.

The latest results show that, after extended follow-up (5.8 years), Zometa continues to be associated with longer median progression-free and overall survival (19 months and 51, respectively), compared to Bonefos (18 months and 46 months, respectively).

For the non-intensive pathway, the thalidomide-based induction therapy improved progression-free survival compared to the MP regimen (13 months versus 12 months), but there was no benefit in terms of overall survival.

In the intensive pathway, there was no statistically significant difference in progression-free and overall survival between the two induction regimens.

Thalidomide maintenance therapy significantly improved progression-free survival compared to no maintenance therapy (22 months versus 16 months).  However, it did not impact overall survival.

Furthermore, thalidomide's benefit in progression-free survival was seen mainly in patients with favorable chromosomal abnormalities.

Chromosomal Abnormalities In Older Myeloma Patients

Dr. Hervé Avet-Loiseau of the Central University Hospital of Nantes, France, presented next. He reviewed the results of a retrospective analysis looking at the prevalence and impact of chromosomal abnormalities in older multiple myeloma patients (that is, those over 65 years of age) (abstract ^[15]).

The analysis was based on data for 1,890 multiple myeloma patients over the age of 65.  Most of the patients were from France.

Dr. Avet-Loiseau and his colleagues divided the patients into two groups: patients 66 to 74 years of age (1,239 patients), and patients over 75 years of age (651 patients).

The researchers first analyzed the occurrence of the del(13), del(17p), and t(4;14) chromosomal abnormalities.

Del(13) occurred in 44 percent of patients ages 66 to 74 and in 37 percent of patients over the age of 75.

For del(17p), the rates were 6 percent in both groups.

For t(4;14), the rates were 11 percent and 8 percent, respectively.

When the results for the older patients in this analysis were compared to results for patients under the age of 65, the researchers observed a lower rate of t(4;14) in elderly patients (14 percent vs 11 percent vs 8 percent). For del(13) and del(17p), there were no statistically significant differences across age groups.

Treatment and follow-up data were available for 1,095 of the patients. The analysis of these data showed that, as in younger patients, both t(4;14) and del(17p) negatively influenced both progression-free survival and overall survival.

Secondary Cancers

The final presentation of the morning was given by Dr. Antonio Palumbo of the University of  Torino in Italy. He summarized the results of a retrospective analysis of the risk of secondary cancer associated with Revlimid and thalidomide treatment (abstract ^[16]).

A myeloma patient experiences a "secondary cancer" if he or she develops another kind of cancer after the patient's initial diagnosis with myeloma.

It was at the 2010 ASH meeting that secondary cancers first became a concern for the myeloma community.

At that meeting, results from several clinical trials showed that treatment with Revlimid may increase a myeloma patient’s risk of developing a secondary cancer (see related Beacon ^[17] news articles).

In the study that Dr. Palumbo summarized on the fourth day of this year's ASH meeting, he and his colleagues examined rates of secondary cancer using data from 2,283 newly diagnosed myeloma patients who had participated in nine different European clinical trials.

The median follow-up time for the patients in this analysis was 29 months. The median patient age was 69 years.

A total of 48 secondary cancers were observed across all 2,283 patients included in the analysis, including 10 blood cancers and 38 non-blood (solid tumor) cancers.

For patients treated with Revlimid, the rates of secondary cancer per 100 years of patient treatment were the following: 0.4 percent for patients also treated with dexamethasone and/or cyclophosphamide, and 0.95 for patients also treated with melphalan.

For patients treated with thalidomide and also with melphalan, the rate of secondary cancer was 1.05 per 100 patient years.

Finally, the rate of secondary cancer for patients treated with only melphalan -- and not Revlimid or thalidomide -- was 0.42 per 100 patient years.

These data indicate that treatment with Revlimid in and of itself may not increase the risk of secondary cancers.

Instead, there may be an interaction between treatment with melphalan and treatment with Revlimid (or thalidomide) that increases a patient's risk of developing secondary cancers.

Dr. Palumbo also presented data showing that the rate of secondary cancer in Revlimid-treated patients in not much different than the age-adjusted rate of cancer in the general population.  Moreover, the risk of developing secondary cancers is generally lower than the risk of a number of serious side effects that can occur during common myeloma treatment regimens.

Additional Coverage Of The ASH 2011 Meeting

This is the last of the Beacon's "daily updates ^[18]" covering myeloma-related research findings presented at the 2011 ASH annual meeting.

However, The Beacon will continue to publish additional articles in the coming weeks with further, in-depth coverage of the research presented at the meeting.