Yesterday, the third day of the American Society of Hematology (ASH) 2011 Annual Meeting in San Diego, was the busiest day of the meeting for people interested in multiple myeloma.  Myeloma-related presentations filled the entire morning and afternoon, and sometimes there were even multiple relevant presentations going on simultaneously.

The morning presentations about therapies combining current myeloma drugs will be covered in this update.  Morning presentations about potential new myeloma therapies were covered in an update published earlier today, and presentations from the rest of the day will be covered in additional updates.

MPR-R Versus MPR Versus MP

Dr. Antonio Palumbo from the University of Torino in Italy presented the final results of a Phase 3 trial aimed at assessing whether Revlimid (lenalidomide) maintenance therapy is beneficial for newly diagnosed, older myeloma patients ineligible for a stem cell transplant (abstract).

The trial tested three treatment regimens.  Two groups of patients received induction (upfront) therapy consisting of melphalan (Alkeran), prednisone, and Revlimid. Then half of the patients were placed on maintenance therapy with Revlimid (MPR-R), while the other half of these patients received a placebo as "maintenance" therapy (MPR).  A third group received only melphalan and prednisone as induction therapy, then a placebo as "maintenance" therapy (MP).

The results of this trial showed that Revlimid maintenance significantly extends progression-free survival.  Median progression free survival was 31 months for the MPR-R group of patients, 14 months for the MPR patients, and 13 months for the MP patients.

However, Revlimid maintenance therapy has not yet impacted overall survival.  The percentage of patients still alive at the four-year mark was 59 percent for the MPR-R group, 58 percent for the MPR group, and 58 percent, as well, for the MP group.

The latest secondary cancer data from the trial indicated that Revlimid maintenance as well as Revlimid induction therapy noticeably increases a patient’s risk of developing a second cancer.  For instance, there were 12 cases of non-invasive second cancers out of 150 patients who received MPR-R, 10 cases out of 152 patients who received MPR, and 4 cases out of 153 patients who received MP.

Dr. Palumbo argued, however, that the increased risk of secondary cancer associated with Revlimid treatment is far outweighed by the drug’s benefits. Most myeloma specialists agree with this perspective, and it is also the conclusion that the European Medicines Agency reached when it reviewed Revlimid's secondary cancer risk this past summer.

Dr. Palumbo said recent results, including those from his trial, are moving myeloma in the direction of continuous therapy rather than specific periods of therapy as has typically been the case in the past.

VMP Versus MP

The next presentation was by Dr. Jesús San Miguel from the University Hospital in Salamanca, Spain.  He presented updated results from a Phase 3 clinical trial comparing the three-drug regimen Velcade (bortezomib), melphalan, and prednisone (VMP) to melphalan and prednisone alone (MP) (abstract).

The goal was to determine if a previously reported overall survival benefit for the VMP regimen persisted after five years of follow-up. In addition, the researchers analyzed the risk of secondary cancers in both treatment groups.

The analysis included 655 patients who were previously untreated and also ineligible for stem cell transplants.  Half of the patients received VMP, and the other half received MP alone.

After about five years of follow up, the median overall survival was 56.4 months for VMP patients versus 43.1 months for MP.

The overall survival benefit of VMP versus MP was also observed for several patient subgroups, including patients 75 years old or older (50.7 months versus 32.9 months), patients with stage III multiple myeloma (42.1 months versus 30.5 months), and patients with kidney disease (56.8 months versus 36.7 months). However, no significant difference in overall survival was observed in patients with high-risk chromosomal abnormalities.

Dr. San Miguel concluded that VMP resulted in a substantial long-term overall survival benefit compared to MP across a range of key patient subgroups, and as was discussed in yesterday’s ASH daily update, the risk of increased secondary cancers associated with the treatment is negligible or non-existent.

VT Versus VP Maintenance Therapy

Dr. San Miguel’s colleague Dr. María-Victoria Mateos then presented results from a Spanish trial that was conducted with older, newly diagnosed multiple myeloma patients who were ineligible to receive a stem cell transplant (abstract).

Patients in this study first received induction therapy with either Velcade, melphalan, and prednisone (VMP) or Velcade, thalidomide (Thalomid), and prednisone (VTP).  They then received one of two possible maintenance regimens: Velcade plus thalidomide (VT) or Velcade plus prednisone (VP).  A total of 178 patients started one of those two maintenance therapies.

In this presentation, Dr. Mateos focused on comparing the results of the maintenance therapies, since she and her colleagues previously published results showing that the two induction treatments tested in this trial had very similar efficacy.

After a median follow-up of 34 months, the complete response rate increased from 24 percent after induction therapy to 42 percent after maintenance therapy.  The complete response rate was similar, but slightly higher for VT versus VP (46 percent versus 39 percent).

The median progression-free survival from the start of induction therapy was 35 months.  From the start of maintenance therapy, the median progression-free survival was 30 months for patients receiving VT and 24 months for patients receiving VP.

The median overall survival was 60 months and was similar for both maintenance regimens.

The VT maintenance regimen had slightly higher levels of side effects, but they were generally not an issue.

Dr. Mateos believed that the benefit in terms of progression-free survival seen for the VT regimen supports pursuing that combination as a preferred maintenance regimen.  However, she also believed side effects could be reduced and the regimen further improved if patients were put on a Velcade-Revlimid maintenance regimen.

VD Versus VTD Versus VMP

Dr. Ruben Niesvizky from the Weill Cornell Medical College in New York presented results from a Phase 3 trial involving older, newly diagnosed, transplant-ineligible multiple myeloma patients.

The 502 patients in the study received 24 weeks of induction therapy with one of three regimens: Velcade plus dexamethasone (Decadron) (VD), Velcade plus thalidomide and dexamethasone (VTD), or Velcade plus melphalan and prednisone (VMP).  All three regimens were followed by an extended 25-week Velcade consolidation therapy.

The three Velcade-based induction regimens were effective, with overall response rates of 73 percent, 80 percent, and 69 percent for VD, VTD, and VMP, respectively.

After a median follow-up of 22 months, the median-progression free survival rates were similar for each of the regimens: 13.8 months for VD, 14.7 months for VTD, and 17.3 months for VMP.

Overall survival rates one-year after the start of treatment were also similar: 87.4 percent for VD, 86.1 percent for VTD, and 88.9 percent for VMP.

Patients receiving VTD experienced the most side effects, while those taking VD had the least side effects.

Overall, Dr. Niesvizky concluded that the three regimens were relatively similar in efficacy but yielded encouraging results for the patient population targeted by the trial.

For more detailed coverage of yesterday’s myeloma-related presentations and research at the ASH meeting, see the ASH 2011 Day Three thread in The Myeloma Beacon discussion forum.

The Beacon is publishing updates from Day Four of ASH in the Beacon’s myeloma forums.  As always, the news from each day will also be summarized in daily updates like this one.