The findings of a recent study indicate that the combination regimen of Revlimid (lenalidomide) and dexamethasone (Decadron) is effective and safe in multiple myeloma patients with reduced kidney function and may even improve kidney function in some patients when the Revlimid dosage is adjusted according to kidney function. The study was published in the European Journal of Haematology.

Because of its effectiveness, the combination of Revlimid and dexamethasone (RD) has become a standard treatment option for patients with relapsed or refractory myeloma. However because Revlimid cannot be broken down effectively by the liver, it circulates throughout the body until it is filtered by the kidneys to be excreted in the urine.

Approximately 20 percent of multiple myeloma patients develop kidney failure, and in 2009, the US Food and Drug Administration (FDA) announced a revision to Revlimid’s prescribing information, warning patients with impaired kidney function to reduce their dosage of Revlimid accordingly (see related Beacon news).

In their study, researchers evaluated the effectiveness of RD therapy in patients with impaired kidney function. Kidney function is assessed by determining how quickly the kidneys filter creatinine, a waste product produced by the muscles. In this study, researchers defined impaired kidney function as creatinine clearance of less than 50 mL/minute.

Researchers recruited 50 patients with relapsed or refractory myeloma who had undergone a median of two therapies prior to the study. Patients were treated with 28-day cycles of Revlimid (days 1 to 21) and dexamethasone (40 mg on days 1 to 4 and 15 to 18 during the first four cycles and on days 1 to 4 from cycle 5 on).

In accordance with FDA safety guidelines, the dosage of Revlimid each patient received was determined based on their creatinine clearance. Patients with normal kidney function, defined in this study as a clearance of 50 mL/minute or greater received the standard dose of 25 mg per day.

Twelve participants (24 percent) had impaired kidney function at the start of the study. Patients with moderate kidney impairment (30 mL/minute to <50 mL/minute) received 10 mg of Revlimid per day. The three patients with severe kidney impairment (<30 mL/minute) who were not on dialysis received 15 mg every other day, and one patient on dialysis was given 15 mg three times a week.

Among the 50 participants, 16 (32 percent) achieved partial response, seven (14 percent) reached very good partial response, and seven (14 percent) complete response, for an overall response rate of 60 percent. There was no difference in overall response between patients with normal kidney function and patients with impaired kidney function (60.5 percent versus 58 percent).

Patients experienced remission for a median of 9 months and overall survival for a median of 16 months. Impaired kidney function did not result in any difference in progression-free and overall survival.

The most common side effects included a reduced white blood cell count (28 percent), fatigue (16 percent), infection (14 percent), a reduced platelet count (1o percent), diarrhea (2 percent) and blood clots in the body’s deep veins (2 percent). Once again, having reduced kidney function did not increase the occurrence of side effects.

Among the 12 patients with impaired kidney function, three achieved complete kidney response, defined as an increase in creatine clearance to 60 mL/minute or greater. Two experienced minor kidney response, defined as a 15 mL/minute to <30 mL/minute increase in the creatinine clearance of someone who has severe kidney impairment.

Researchers concluded that adjusting Revlimid dosage according to kidney function results in the same rate of response and does not negatively impact progression-free and overall survival or rate of side effects. Furthermore in some cases, the Revlimid-dexamethasone therapy improved kidney function. They recommended further studies examining RD therapy’s effectiveness in patients with severe kidney function and as an agent for improving kidney function.

For more information, please see the European Journal of Haematology (abstract).