Revlimid ^[1] (lenalidomide) is an effective maintenance therapy after stem cell transplantation in multiple myeloma patients, according to two Phase 3 studies presented on Sunday at the annual meeting of the American Society of Clinical Oncology (ASCO).

Based on the results of these two studies as well as a previous study ^[2], Revlimid maintenance therapy is likely to become a common addition to the treatment of myeloma.

Dr. Sergio Giralt of the MD Anderson Cancer Center in Houston led a discussion about these two studies during which he said, “[These are] two of the most important practice-changing presentations that have happened in myeloma over the last couple of years.”

The first study, which was conducted in the United States, found that Revlimid delayed time to disease progression. The second study, which was conducted in France, found that Revlimid extended progression-free survival.

United States CALGB 100104 Study

The U.S. study investigated whether maintenance therapy with Revlimid prolonged the time to progression (TTP) after single autologous stem cell transplantation.

Approximately 100 days after transplantation, patients who had at least stable disease were randomly assigned to receive either Revlimid or placebo until disease progression. Patients were initially given a dose of 10 mg of Revlimid per day. The dosage was increased to 15 mg/day after three months.

Initial results from December 2009 had indicated that Revlimid extends progression-free survival (see related Beacon ^[3] news).

At ASCO, Dr. Philip McCarthy of Roswell Park Cancer Institute in Buffalo, New York presented updated results of the 568-patient study. “Maintenance therapy with Revlimid compared to placebo significantly prolongs time to progression,” reported Dr. McCarthy.

Dr. McCarthy and his colleagues found that 14 percent of patients on Revlimid had relapsed compared to 28 percent who received the placebo, putting Revlimid patients at a 58 percent lower risk of progressing than placebo patients.

The estimated median TTP for patients who received the placebo was 22.5 months. The median TTP for patients who received Revlimid has not yet been reached, indicating that Revlimid as a maintenance therapy significantly delays TTP.

After one year of observations, there is no difference in overall survival between the two groups. However, physicians are hopeful that longer follow-up will show a significant difference.

“We are obviously anxious to know if this longer remission will translate into improved survival,” said Dr. Brian Durie of Cedars Sinai in Los Angeles and the International Myeloma Foundation.

Although Revlimid maintenance delays progression, it appears to have a higher rate of serious side effects, including low white blood cells (42 percent versus 7 percent), low platelets (12 percent versus 3 percent), and low red blood cells (6 percent versus 1 percent). Dr. McCarthy said that the side effects were manageable.

In December 2009, due to the positive results, patients were notified about whether they were receiving Revlimid maintenance or placebo. Patients on placebo were allowed to choose whether they wanted to switch to Revlimid maintenance, and 87 percent have chosen to begin maintenance.

French IFM 2005-02 Study

A group of French researchers investigated Revlimid, molecularly similar to thalidomide ^[4] (Thalomid), as maintenance treatment after they found that effective maintenance therapy with thalidomide was associated with peripheral neuropathy (numbness and tingling in the hands, arms, legs, and feet). Revlimid is not known to induce peripheral neuropathy.

Patients received short-term Revlimid (25 mg per day on days 1 to 21 in a 28-day cycle) for two months as consolidation therapy after autologous stem cell transplantation to help patients maintain remission. Patients were then randomly assigned to receive long-term, continuous, low-dose maintenance therapy with Revlimid (10 to 15 mg per day) or placebo until relapse.

Preliminary results from December 2009 showed that consolidation therapy with Revlimid helped more patients achieve complete remission than transplantation alone. Those results also indicated that maintenance therapy extended progression-free survival (see related Beacon ^[5] news).

Dr. Michel Attal of the University Hospital in Toulouse, France presented at ASCO the updated results of the 614-patient study.

The researchers found that consolidation therapy with Revlimid improved responses in 20 percent of patients. More patients achieved complete responses and very good partial responses after consolidation. Likewise, a few additional patients achieved complete remission on maintenance therapy.

Additionally, maintenance therapy with Revlimid improved progression-free survival: 68 percent of patients on Revlimid had not progressed after three-years of maintenance therapy compared to 34 percent of patients who received the placebo.

The estimated median progression-free survival for patients who received the placebo was 24 months, while the median for the placebo group has not yet been reached

Dr. Attal and his colleagues found that patients benefited from Revlimid maintenance therapy regardless of whether or not they achieved a complete response after transplantation.

After three years of maintenance therapy, which is four years after diagnosis, overall survival was 80 percent for the placebo group and 88 percent for the maintenance group. However, the two rates are not significantly different. Dr. Attal said that 88 percent survival four years after diagnosis is “unprecedented.”

The rate of severe side effects in this study were all low, with low white blood cells being the most common (7 percent in the maintenance group, and 1 percent in the placebo group).

Attendees at the presentation were surprised that the rate of low white blood cells in this study was much lower than the rate in the U.S. study. Given the low rate, one attendee asked whether the French group would be studying a higher dose of Revlimid maintenance. However, Dr. Attal said that was not currently in their plans.

“What is most important about this study is that the benefit of Revlimid is seen regardless of response to transplant,” said Dr. Giralt.

Recommendations

Based on the results of these two studies, Dr. Giralt recommended that after transplantation, patients with residual disease as well as high-risk patients in remission should use Revlimid maintenance. Only in the case of patients with low tumor mass and low-risk disease is it unclear whether they should remain under careful observation or begin maintenance. For patients who are currently on thalidomide maintenance and responding well, they should continue with their current therapy.

For more information on the studies, visit abstract 8017 ^[6] (U.S. study) and abstract 8018 ^[7] (French study) at the ASCO meeting ^[8] website.