Results of an Italian study show that patients taking Revlimid who progressed on thalidomide had similar overall response and survival rates as patients taking Revlimid who discontinued thalidomide after achieving at least a partial response.

Based on these results, the study authors concluded that Revlimid ^[1] (lenalidomide) may be equally effective in myeloma patients who previously progressed on thalidomide and myeloma patients who previously responded to thalidomide.

Revlimid and thalidomide ^[2] (Thalomid) belong to the same class of drugs called immunomodulatory agents; however, they produce different side effects. Compared to thalidomide, Revlimid is associated with more cases of low blood counts and fewer cases of nerve-related disorders, such as nerve damage in the extremities.

Results of previous trials showed that patients who had previously received thalidomide achieved higher overall response and progression-free survival rates with Revlimid and dexamethasone ^[3] (Decadron) than with dexamethasone alone.

To further evaluate the impact of previous thalidomide therapy on Revlimid response, researchers from Italy retrospectively analyzed data from 106 relapsed or refractory myeloma patients who had received thalidomide with either dexamethasone or chemotherapy from January 2001 to May 2009 and Revlimid-dexamethasone salvage therapy from March 2007 to March 2010. The median number of previous therapies ranged from one to six.

All 106 patients received Revlimid at 25 mg per day for 21 days of a 28-day cycle and either high-dose or low-dose dexamethasone.

Of the 106 patients, 80 were considered thalidomide-resistant because they had progressed on thalidomide; 26 were considered thalidomide-sensitive because they had discontinued thalidomide after achieving at least a partial remission.

Of the 26 thalidomide-sensitive patients, 22 had discontinued thalidomide because of serious side effects, including nerve damage in the extremities, low white blood cell counts, and infections.

The researchers found that 56 percent of the thalidomide-resistant patients responded to Revlimid, with 10 percent achieving a complete remission, 6.2 percent achieving a very good partial remission, and 40 percent achieving a partial remission.

Sixty-two percent of the thalidomide-sensitive patients responded to Revlimid, with 7.7 percent achieving a complete remission, 3.8 percent achieving a very good partial remission, and 50 percent achieving a partial remission.

The median progression-free survival was 10 months for thalidomide-resistant patients and 12 months for thalidomide-sensitive patients.

The median overall survival was 17 months for thalidomide-resistant patients, compared to 18.5 months for thalidomide-sensitive patients.

The study authors pointed out that disease stage, number of prior lines of therapy, and response to previous Velcade ^[4] (bortezomib)-based therapies did not affect the patients’ response to Revlimid.

Low white blood cell count was the most common side effect, occurring in 16.2 percent and 23 percent of thalidomide-resistant patients and thalidomide-sensitive patients, respectively.

Low platelet count and blockage of lung arteries affected more thalidomide-sensitive patients than thalidomide-resistant patients. Infections and nerve and muscle disorders occurred only in thalidomide-resistant patients. Twelve percent of the thalidomide-resistant patients and 7.7 percent of the thalidomide-sensitive patients discontinued Revlimid because of side effects.

“Revlimid is a great drug and it should be tried whether or not a patient previously failed thalidomide,” said Dr. Leif Bergsagel, Professor of Therapeutics for Cancer Research at the Mayo Clinic in Arizona, who was not involved in the study.

However, he added that the chance of response to Revlimid will always be higher in a patient who has never received thalidomide before because Revlimid and thalidomide belong to the same class of drugs.

”Prior exposure to a class of drug reduces the subsequent efficacy of that class,” he explained.

In his opinion, it is best to alternate classes of therapies. “Use a proteasome inhibitor combination following relapse from (or progression on) an IMID [immunomodulatory agent], an IMID on relapse from a proteasome inhibitor, an alkylator on relapse from IMID-proteasome inhibitors, etc.,” he explained.

For more information, please see the study in the European Journal of Cancer ^[5] (abstract).