Abstract

Background: Renal dysfunction is a common consequence of MM. Patients can present with varying degrees of renal impairment during the course of their disease. Clinical management of these patients remains a challenge and the role of newer agents like bortezomib is still being defined in them. We have previously reported on the safety and efficacy of bortezomib in MM patients with advanced renal failure requiring dialysis. Here we further evaluate if varying degree of renal dysfunction as determined by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF K/DOQI), adversely affects the clinical outcome of bortezomib-based therapies.

Methods: All MM patients treated with bortezomib or bortezomib-based therapies were evaluable for this analysis. Response to treatment was classified as per EBMT criteria. Renal function stratification was done for all the patients based on NKF K/DOQI guideline stages as per glomerular filteration rate (GFR; ml/min/1.73 m2). Stages 1, 2, 3, 4 and 5 were defined as GFR ≥ 90, 60–89, 30–59, 15–29, and < 15/dialysis, respectively. To study the statistical relationship between pairs of nominal variables, Fisher’s exact test was used. To study the statistical relationship between nominal and ordinal variables, exact Wilcoxon test was used. A 0.05 nominal significance level was used in all testing.

Results: Sixty six consecutive patients were evaluable. Amongst these, 32 (48.5%) were females and 34 (51.5%) males with a median age of 59.5 years (range 40–82 years). Fifty five (83%) patients had advanced MM; stage > I as per Durie-Salmon (DS) criteria. Eligible patients had either relapsed/refractory disease (n=33) or were previously untreated (n=33). NKF K/DOQI renal function stages were 1, 2, 3, 4 and 5 in 9 (13.6%), 29 (44%), 22 (33.4%), 3 (4.5%) and 3 (4.5%) patients, respectively. Clinical response observed was complete remission (CR) in 8 (12%), partial remission (PR) in 25 (38%), stable disease (SD) in 27 (41%) and progressive disease (PD) in 6 (9%) patients. There was no significant association between renal function and patient age (p = 0.0808; 95% CI -0.0246, 0.4367), DS stage (p = 0.1722; 95% CI -0.0806, 0.4744), Ig type (p = 0.5288), untreated vs. relapsed/refractory disease (p = 0.1352), or response to treatment (p = 0.5292; 95% CI -0.1601, 0.3114).

Conclusions: In this paper we investigated the correlation of NKF K/DOQI renal function stage in myeloma patients with clinical response to bortezomib. We noted that patients treated with bortezomib-based therapies experienced similar clinical benefit irrespective of the NKF K/DOQI renal function stage. These findings further support our previous observation that bortezomib is an effective therapeutic option for MM patients with renal dysfunction.

Best Response to Treatment in Each NKF K/DOQI Stage

StageBest Response To Treatment
NKF K/DOQI; National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative, PD; Progressive Disease, SD; Stable Disease, PR; Partial Remission, CR; Complete Remission 
 PD SD PR CR Total 
14 10 29 
22 
Total 27 25 66 
StageBest Response To Treatment
NKF K/DOQI; National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative, PD; Progressive Disease, SD; Stable Disease, PR; Partial Remission, CR; Complete Remission 
 PD SD PR CR Total 
14 10 29 
22 
Total 27 25 66 

Author notes

Disclosure:Consultancy: Millennium Pharmaceuticals. Ownership Interests:; Millennium Pharmaceuticals.