LENALIDOMIDE MAINTENANCE FOR MULTIPLE MYELOMA

May 26 2010 — Patients with multiple myeloma who were treated with high-dose chemotherapy and autologous stem cell transplantation and then went on to receive maintenance therapy with lenalinomide (Revlimid) were half as likely to relapse as patients who were received placebo.

"These results are very promising," said lead researcher Michel Attal, PhD, professor of hematology at Purpan Hospital in Toulouse, France. He emphasized that lenalinomide was very well tolerated, in contrast to thalidomide, which had rate-limiting toxicity when investigated as maintenance therapy in this setting.

Dr. Attal was speaking during a presscast that highlighted several presentations that will be made at the upcoming American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.

These results, from an interim analysis of data from a phase 3 study conducted by the Intergroupe Francophone du Myélome, are due to be presented on June 6. A final analysis of these data is due out in December, he said.

Significant Improvement in Progression-Free Survival

The trial involved 614 patients with multiple myeloma who had received an autologous stem cell transplantation and high-dose chemotherapy induction (most with the combination of vincristine, doxorubicin, and dexamethasone or with bortezomib plus dexamethasone, although others were also used).

All patients were then given lenalinomide consolidation therapy (25 mg/day for 21 days a month for 2 months). This improved the response in 20% of patients, Dr. Attal reported.

Patients were then randomized to receive either placebo or lenalinomide maintenance therapy (10 to 15 mg/day) until relapse.

Maintenance therapy significantly improved 3-year progression-free survival to 68%, compared with 35% for placebo (hazard ratio [HR], 0.46; P < 106), reducing the rate of relapse by 54%.

These results suggest that "maintenance therapy with lenalinomide can improve quality of life in patients with myeloma by delaying the need for more intensive therapy to treat a relapse," Dr. Attal explained.

Current ASCO president Doug Blayney MD, medical director of the Comprehensive Cancer Center at the University of Michigan in Ann Arbor, said that myeloma is another cancer that is moving into the chronic disease category, with patients kept on maintenance therapy to keep the disease in remission and prevent the recurrences, which are "devastating and painful."

At the same presscast, new data on follicular lymphoma showing that rituximab maintenance therapy halves the risk for relapse were also discussed, and several parallels were drawn between that situation and this one. In both cases, the maintenance therapy can be cost-saving; treating relapses when they occur is expensive, experts noted. But there is also a huge benefit to patients who can continue with their normal lives while receiving maintenance therapy, which is of "major clinical importance to patients," Dr. Attal noted.

Expect to See Survival Benefit

There remains a question of whether lenalinomide maintenance therapy will improve overall survival in multiple myeloma. So far the data are out to 24 months, and the survival curves are similar (88% for lenalinomide, 80% for placebo), Dr. Attal said.

"But I would be surprised not to see an improvement in survival over the long term because of the dramatic effect on progression-free survival," Dr. Attal said.

"I have been doing clinical trials in multiple myeloma for 25 years now, but I have never seen such a large effect on progression-free survival," he added. "I have seen smaller effects, and all of these have converted in time to survival benefits."

No Standard for Maintenance Therapy

Current treatment approaches to multiple myeloma were discussed in detail in a recent CME program posted on Medscape Oncology. Regarding maintenance therapy, experts concluded that there is currently "no standard, but a highly individualized approach." A survey of community physicians showed that all used a maintenance therapy after autologous stem cell transplantation, with the most popular drug for maintenance being bortezomib (50% of responders), followed by lenalinomide (17% using it in all patients and another 17% using it only in patients with a high risk for relapse); the remaining 17% said they used thalidomide for maintenance.

Dr. Attal reports acting as a consultant or advisor to Celgene and Janssen-Cilag, and receiving research funding from Celgene, as do several of his coauthors.

American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract 8018. To be presented June 6, 2010.