Renal Safety of Ibandronate in the Treatment of Myeloma Patients.

Treatment of myeloma bone disease with bisphosphonates is standard of care. But renal toxicity due to bisphosphonate treatment tends to be a major problem in myeloma patients, especially. Patients with reduced kidney function and patients who have switched bisphosphonate drugs are at highest risk. Toxicity appears typically after few months of treatment. In patients with myeloma and impaired renal function with GFR < 30 ml/min no bisphosphonate is approved for treatment of myeloma bone disease in Germany. In breast cancer patients ibandronate dosage should be reduced from 6 to 2 mg in advanced kidney failure (GFR < 30 ml/min).

We evaluated safety data about renal function from myeloma patients, who were treated with ibandronate. The patients were stratified according to pre-treatment and kidney function.

In a prospective non-interventional study (NIS) about safety and efficacy of ibandronate in breast cancer patients it turned out that unintentionally myeloma patients were also included. Out of 3528 documented patients 93 myeloma patients were identified. We evaluated the data from these myeloma patients separately.

The myeloma patients were subdivided in 4 groups according to their renal function: GFR > 90 (stage 1), 60 – 90 (stage 2), 30 – 59 (stage 3) and < 30 (stage 4-5) ml/min. Since pre-treatment with or without bisphosphonates could be of influence, patients were analysed according to former pre-treatment: no bisphosphonate (I), ibandronate (II), and other bisphosphonates (III). The kidney function was calculated every month over a period of six months.

Ninety-three (93) patients with multiple myeloma were available for evaluation. In 87 patients renal function was documented over a minimum of 5 months. Eleven (11) patients had stage 1, 34 patients had stage 2, 36 patients stage 3 and 12 patients stage 4-5 of renal impairment, respectively. There were no differences in renal function according to their pre-treatment. There were also no differences in the three groups (I-III) regarding the prevalence of diabetes, hypertension and kidney function. A total number of 620 infusions were documented. The ibandronate dosage was 6 mg in 89% of all infusions, 4 mg in 4%, 3 mg in 2% and 2 mg in 5%, respectively. In the subgroups (stages) renal function was stable over time (mean GFR+/-SD ; difference over the time [ml/min]: stage 1: 116,8+/- 20,9; - 3,38; stage 2: 74,7 +/- 8.4; +2,04; stage 3: 46,1 +/- 8,1; +3,7; stage 4-5: 20,4 +/- 7; + 13,37; all changes n. s.), but there was a trend for improved renal function in patients with renal function stage 4-5. The mean changes were similar in all groups irrespectively of the pre-treatment. In 8 patients the treatment was terminated prematurely. Three patients had disease progression, and two patients died due to myeloma during study period. Two patients were lost by follow up and one patient declined further treatment.

The data of this non-interventional study suggest that there is no evidence for renal toxicity of ibandronate in myeloma patients in all stages of renal function. This applies also for patients who received higher dosages of ibandronate as recommended. Patients with worse kidney function (stage 4-5) had a trend of improvement of renal function over the study period, however the changes were not significant due to the limited number of patients. There were also no differences in renal function irrespectively of the pre-treatment.

Bergner:Roche Pharma AG: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Ibandronate is not approved for use in myeloma bone disease.