A new study published in the journal Leukemia determined that when treated with Revlimid (lenalidomide) and dexamethasone (Decadron), relapsed and refractory myeloma patients with genetic risk factors experience lower response rates and shorter progression-free and overall survival durations.

Researchers also discovered that prior treatment with thalidomide (Thalomid) was associated with a decreased progression-free and overall survival.

Multiple myeloma patients with the chromosomal abnormalities del(13), t(4;14) or del(17p) are associated with a poorer prognosis in response to traditional chemotherapy. However, new drug and treatment options have the potential to overcome this poor prognosis. In particular, the relatively new combination of Revlimid and dexamethasone (RD) has proven highly effective in treating patients with relapsed or refractory myeloma.

Studies examining whether the RD combination can overcome the disadvantages associated with genetic risk factors like del(13), t(4;14), and del(17p) have given mixed results. In this retrospective study, researchers evaluated the impact of genetic risk factors and prior treatment on patient outcome in response to the RD combination therapy.

Researcher collected the medical records of 207 relapsed and refractory myeloma patients who had been treated with Revlimid and dexamethasone. Patients received a median of five 28-day cycles of Revlimid (25 mg/day on days 1 to 21) and dexamethasone (40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 during cycles 1 to 4; days 1 to 4 from cycle 5 on).

Prior to Revlimid-dexamethasone therapy, patients had undergone a median of three treatments with drugs such as Velcade (bortezomib), thalidomide, or high-dose melphalan (Alkeran). Researchers also determined how many patients had genetic risk factors. Out of 191 patients tested for del(13), 41 percent had the abnormality. Out of the 184 patients tested for t(4;14), 14 percent had the abnormality, and seven percent of the 120 patients tested for del(17p) had the abnormality.

The overall response rate (ORR), defined as the rate of people achieving partial response or better, was 59 percent. Fourteen percent of patients reached very good partial response and seven percent showed a complete response. The median remission duration was 9.6 months, and the median overall survival was 15.1 months.

In patients with del(13), the overall response rate was significantly lower in comparison to patients without the risk factor (43 percent versus 71 percent). Median progression-free and overall survival were also significantly shorter (PFS: 5.0 months versus 12.5 months; OS: 10.4 months versus 17.4 months).

The same pattern was observed in patients with t(4;14). Patients with t(4;14) experienced a 39 percent overall response rate, a 5.5-month remission duration, and a 9.4-month overall survival’ whereas patients without t(4;14) had a 62-percent ORR, a 10.6-month PFS, and a 15.4-month OS.

There were too few del(17p) patients to perform a meaningful statistical analysis.

In terms of treatment history, patients who had previously been treated with Velcade had significantly lower overall response rates to the RD combination than those who had not (55.4 percent versus 74.3 percent). They also experienced shorter median progression-free survival (8.3 months) and overall survival time (12.2 months). In patients who had no prior Velcade history, median progression-free and overall survival periods had not been reached yet.

While no difference was observed between patients with thalidomide history and those without, researchers discovered that patients who had progressed after thalidomide treatment had a shorter progression-free and overall survival than those who had not progressed (PFS: 5.7 months versus 15.7 months; OS: 9.7 months versus 16.1 months).

The researchers determined that the del(13) abnormality could be used to predict overall response and remission duration, with the presence of del(13) correlating with lower response rates and shorter progression-free survival. The number of prior therapies a patient had undergone also proved to be a predictor of overall response rate, with more prior therapies correlating with lower response rates. They added that progression during thalidomide therapy may be a predictor of a shortened overall survival and reduced response duration.

For more information, please see the journal Leukemia (abstract).