The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment

Abstract

Background: Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.

Aim: To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.

Methods: The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.

Result: The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.

Conclusion: High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.

Figure 1. Patients enrolled in this study.

Figure 2. Overall survival in symptomatic multiple myeloma patients.

(A) Patients presenting with renal impairment compared to those with normal renal function. (B) Patients divided into five groups according to the chronic kidney disease classification.

Figure 3. Overall survival for non-high-dose treated (non-HDT) patients with renal impairment.

(A) Patients treated with novel agents (bortezomib, thalidomide or lenalidomide) compared to conventional agents in the 1^st treatment line. (B) Patients treated with bortezomib compared to conventional agents in the 1^st treatment line.

Figure 4. Overall survival in non-high-dose treated (non-HDT) patients with and without renal impairmet treated with novel agents.

(A) Patients with renal impairment compared to those without renal impairment after the use of novel agents (bortezomib, lenalidomide or thalidomide) in the 1^st treatment line. (B) Patients with renal impairment compared to those without renal impairment after the use of bortezomib in the 1^st treatment line.

Figure 5. Response distribution after the 1^st treatment line in patients with and without renal impairment.

Comparing the population treated with novel agents (bortezomib, lenalidomide or thalidomide) to the population treated with conventional agents. (A) Patients with renal impairment. (B) Patients without renal impairment. NR, no response; PR, partial response; ≥VGPR, at least very good partial response.

Figure 6. Time to next treatment in patients with and without renal impairment at diagnosis.

(A) In high-dose treated (HDT) patients with and without renal impairment after 2^nd line of therapy. (B) In non-HDT patients with and without renal impairment after 2^nd line of therapy. (C) Non-HDT patients with renal impairment treated with novel agents (bortezomib, lenalidomide or thalidomide) in the 1^st line compared to those treated with conventional agents (Conv.). (D) Non-HDT-patients with renal impairment treated with bortezomib (Bz) in the 1^st line compared to those treated with conventional agents. (E) HDT-patients with renal impairment treated with novel agents (bortezomib, lenalidomide or thalidomide) in the 1^st line compared to to those treated with conventional agents.