Renal Impairment and the Use of Bisphosphonates in Patients with Multiple Myeloma: Retrospective Analysis of 114 Patients with Respect to Age and Other Clinical Characteristics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4918-4918
Author(s):  
Sam Mazj ◽  
Stuart M. Lichtman
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Renal Toxicity ◽  
Clinical Course ◽  
The Elderly ◽  
Close Monitoring ◽  
Renal Function Deterioration ◽  
The Impact

Abstract Backgound: The clinical course of multiple myeloma is often associated with significant bone related morbidity. This can be modified by the use of bisphosphonates. Studies have shown renal toxicity associated with different bisphosphonates especially following the exposure of zoledronic acid. Published literature suggests renal function deterioration occurs in 8.8–15.2% of patients at recommended dose of 4 mg infused intravenously over 15 minutes. Methods: We retrospectively reviewed the records of all patients with multiple myeloma who received bisphosphonates during the period of January 2002-June 2004 at our institution. 114 patients were analyzed (male/female 63/51; age-median 69;mean 71;range 40–92). 61 (54%) were >70 years of age. They received a total of 1301 doses (mean 11.4) during this period. The type of bisphosphonate used was: zolendronate: 58; pamidronate: 23; pamidronate changed to zolendronate (both) : 33. Patients were categorized to the type and sequence of bisphosphonates [ pamidronate vs. zoledronate and pamidronate followed by zoledronate (both) ], age and sex. Renal dysfunction was defined as an increase in serum creatinine of >0.5 mg/dl over baseline. Results: There were 19 patients (16.7%) who developed renal dysfunction. 15 of the 19 episodes (79%) occurred in the 70 years and older group. The table shows the distribution of patients, type of bisphosphonate and the distribution of patients with renal toxicity. Conclusion: This analysis showed increase in renal dysfunction occurs in all ages with use of bisphosphonates. The elderly may be particularly susceptible to this toxicity. Although we have not analyzed the impact of associated comorbidities (including type of multiple myeloma) leading to renal insufficiency in this study, the elderly patients may need more close monitoring of renal function with the use of bisphosphonates. Age and renal impairment with bisphosphonate use Age Zolendronate Pamidronate Both Total Number in paranthesis indicates the renal impairment case 40–49 6 (0) 2 (0) 2 (0) 10 (0) 50–59 10 (0) 1 (0) 4 (0) 15 (0) 60–69 14 (2) 3 (0) 11 (1) 28(3) 70–79 19 (3) 9 (1) 14 (4) 42 (8) 80+ 9 (3) 8 (0) 2 (4) 19 (7) Total 58 (9) 23 (1) 33 (9) 114 (19)

Open-Label Study of Ibandronate in Elderly Myeloma Patients with Pre-Existing Renal Deterioration.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3459-3459
Author(s):  
Dirk Henrich ◽  
Raoul Bergner ◽  
Martin Hoffmann ◽  
Andrea Honecker ◽  
Dietmar Nagel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Renal Toxicity ◽  
The Elderly ◽  
Tubular Damage ◽  
Open Label ◽  
Open Label Study ◽  
Urinary Markers ◽  
Renal Safety

Abstract Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic bone pain, improving quality of life in patients with malignant bone disease. However, clinical studies have highlighted that some, but not all intravenous (i.v.) bisphosphonates are associated with an increased risk of renal toxicity. The renal safety of bisphosphonates is particularly important in patients with multiple myeloma or in the elderly, who often have some degree of underlying renal damage and are at high risk of renal failure. In phase III trials, the renal safety profile of i.v. ibandronate was comparable to placebo. This agent may therefore be suitable for use in patients with impaired renal health. The current open-label study assessed the renal safety of ibandronate in elderly patients with multiple myeloma and varying stages of pre-existing renal impairment. Patients with multiple myeloma (creatinine clearance 8–139mL/min) received i.v. ibandronate (6mg, infused over 30 minutes). For each patient, deterioration in renal function was graded at baseline using creatinine clearance (grade 0: ≥80, 1: 50–79, 2: 30–49, 3: <30mL/min). Urinary markers of tubular damage (α-glutathione-S-transferase [α GST] and β-N-acetyl-glucosaminidase [βNAG]) were measured at baseline and at 24 and 72 hours following ibandronate infusion. Follow-up toxicity data was collected over 6 months for a subset of patients (n=6). A total of 29 patients (15 females and 14 males; mean age 71.1 ± 5 years) were included in this study. At baseline, four patients had a normal renal function (grade 0). The remaining 25 patients had varying degrees of renal insufficiency (grade 1: n=6, grade 2, n=8, grade 3: n=11). Mean proteinuria was 1799 ± 2140mg/24 hours. Serum creatinine and levels of urinary markers (α GST and βNAG) remained stable throughout the study. There was a statistically non-significant decrease in βNAG, and a positive correlation between ibandronate elimination and creatinine clearance. In the subset of six patients receiving six additional monthly infusions, ibandronate had no negative impact on renal function. To conclude, in this study of elderly patients with multiple myeloma, ibandronate was well tolerated and did not compromise renal health, despite 86% (25/29) of patients having pre-existing renal insufficiency. This was evidenced by markers of tubular damage and renal function, which remained unchanged throughout the study period. Furthermore, a subset of patients who received repeated ibandronate infusions did not experience renal toxicity. The management of drug-related nephrotoxicity needs special attention in patients with multiple myeloma, and in the elderly. These data suggest that ibandronate may be suitable for use in high risk multiple myeloma patients with pre-existing renal impairment. Further studies in larger groups of patients are warranted.

Impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect MM Registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
Sikander Ailawadhi ◽  
Hans Chulhee Lee ◽  
Jim Omel ◽  
Kathleen Toomey ◽  
James W. Hardin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Progression Free Survival ◽  
Induction Treatment ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Front Line ◽  
Real World Data ◽  
The Impact

8518 Background: Patients (pts) with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI) are often excluded from clinical trials. Data are limited on the effects of induction treatment in these pts, who may also be ineligible for autologous stem cell transplant (SCT) due to severity of RI. This analysis investigated the impact of RVd induction on renal function in transplant eligible (TE) and noneligible (TNE) pts from the Connect MM Registry, a US, multicenter, prospective, observational study. Methods: Eligible pts were ≥ 18 y and had symptomatic MM diagnosed ≤ 2 mos prior to enrollment, as defined by the International Myeloma Working Group criteria. For this analysis, pts that received front-line RVd for ≥ 3 cycles were grouped per transplant eligibility and renal function at baseline (BL; creatinine clearance [CrCl] < 30, 30-50, > 50-80, and > 80). Pts with progressive disease at BL were excluded. Renal function at 3 mos was measured. Median unadjusted progression-free survival (PFS) was calculated from start of regimen in TE and TNE populations, with pts grouped by CrCl (≤ 60 or > 60) at BL. Results: As of 7/23/19, 421 TE and 212 TNE pts received RVd for ≥ 3 cycles. TE and TNE pts were grouped by BL CrCl of < 30 (20 and 16 pts), 30-50 (36 and 50 pts), > 50-80 (117 and 63 pts), and > 80 (248 and 83 pts). Renal function improvement was observed in all pts receiving RVd, including those with moderate (30-50 CrCl) and severe (< 30 CrCl) RI at BL (Table). In pts with > 60 CrCl and ≤ 60 CrCl at BL, median PFS in TE pts was 48.6 mos and 43.2 mos, respectively. In TNE pts, median PFS was 36.4 mos and 30.6 mos, respectively. Conclusions: The results from the Connect MM Registry indicate that pts with NDMM and RI (including moderate and severe) who receive front-line RVd for ≥ 3 cycles may see improvement in renal function at 3 mos, regardless of transplant eligibility. RVd therefore can potentially be used in pts with RI. This analysis provides real-world data that support further investigation of RVd treatment in pts with moderate or severe RI. Clinical trial information: NCT01081028 . [Table: see text]

The International Scoring System (ISS) for Multiple Myeloma Remains a Robust Prognostic Tool Independently of Patients' Renal Function

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3036-3036
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Marie-Christine Kyrtsonis ◽  
John Meletis ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Median Survival ◽  
Staging System ◽  
Tumor Burden ◽  
Prognostic Performance ◽  
Stage 4 ◽  
Stage 1

Abstract Abstract 3036 The ISS introduced by Greipp et al (J Clin Oncol 2005) represents today the most widely used staging system for patients with multiple myeloma (MM) because it is based on two readily available variables: serum albumin and beta2-microglobulin. Serum beta2-microglobulin not only reflects myeloma tumor load but it is also increased in patients with renal dysfunction. Thus, there have been concerns that ISS-3 stage may include MM patients with renal impairment in whom elevated beta2-microglobulin does not reflect tumor burden but rather the degree of renal dysfunction. To address this issue, we assessed the impact of patients' renal function on the prognostic performance of ISS. Our analysis included data from 1516 patients with symptomatic MM that had been entered into the database of the Greek Myeloma Study Group. Renal function was assessed by the estimated GFR (eGFR), which was calculated using the modified MDRD formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American) and the degree of renal dysfunction was staged according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) classification of chronic kidney disease (CKD) as follows: stage 1 eGFR ≥90 ml/min; stage 2 eGFR of 60–89 ml/min; stage 3 eGFR of 30–59 ml/min; stage 4 eGFR of 15–29 ml/min and stage 5 eGFR <15 ml/min or under dialysis. At the time of treatment initiation, 788 patients had stage 1 or 2 CKD and 728 patients had stage 3–5 CKD. According to ISS, 29% patients had ISS-1, 38% patients had ISS-2 and 33% ISS-3. Renal impairment was significantly more common in ISS-3 patients: 76% of ISS-3 patients had stage 3–5 CKD compared to 42% and 27% for ISS-2 and ISS-1, respectively (p<0.001). Similarly, the incidence of stage 4 or 5 CKD was higher in ISS-3 (23% and 20%, respectively) than in patients with ISS-2 (6% and 1.5%, respectively) or ISS-1 (4% and 1%, p<0.001). In the univariate analysis, which included all patients, stage 3–5 CKD was associated with inferior survival (31 months vs. 51 months for those with stage 1 or 2 CKD, p<0.001). However, CKD stages had not an independent prognostic value in the multivariate analysis. Subsequently, we analyzed the prognostic significance of renal function in each ISS group separately. ISS-1 patients with stage 1 or 2 CKD had a median survival of 76 months vs. 56 months for patients with stage 3–5 CKD (p=0.053). In ISS-2, the respective median survival was 49 months and 29 months for stage 1–2 CKD vs. stage 3–5 CKD (p=0.02). In contrast, in patients with ISS-3 the median survival was similar (30 vs. 24 months, p=0.292) for patients with stage 1–2 CKD and stage 3–5 CKD. Multivariate analysis performed in each ISS subgroup revealed that renal function (either as a dichotomous or as a continuous variable) was not an independent prognostic factor in any of ISS stages: HR=1.031, p=0.873 for ISS-1; HR=0.996, p=0.123 for ISS-2 and HR=1.09, p=0.6 for ISS-3. We conclude that ISS is a simple, yet powerful prognostic staging system. The robustness of ISS remains unaffected by the degree of renal function. In patients with ISS-3, which includes many patients with renal dysfunction, elevated beta2-microglobulin reflects tumor burden, despite its increase due to renal impairment. Our data in a large population of myeloma patients indicate that adjustment for renal function will not improve the prognostic performance across all ISS stages. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cardiac and renal complications of carfilzomib in patients with multiple myeloma

2017 ◽  
Vol 1 (7) ◽  
pp. 449-454 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Erasmia Psimenou ◽  
Dimitrios Ziogas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Toxicity ◽  
Renal Complications ◽  
Key Points

Key Points Carfilzomib is associated with reversible cardiotoxicity in 12% of consecutive myeloma patients. Transient renal toxicity is common, but carfilzomib may improve renal function in myeloma-related renal impairment.

Renal Impairment Is Not An Independent Adverse Prognostic Factor In Multiple Myeloma Patients Who Are Treated Upfront with Novel Agent-Based Regimens

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3033-3033 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
Prognostic Impact ◽  
Agent Based ◽  
Stage 1 ◽  
Novel Agent

Abstract Abstract 3033 The adverse prognosis of renal impairment in patients with multiple myeloma (MM) has been reported in several series. However, the prognostic impact of renal dysfunction on the survival of MM patients who are treated upfront with novel agents has not been clearly defined. To address this question we studied 180 consecutive patients who received upfront novel agent (thalidomide, bortezomib or lenalidomide)-based regimens, in a single center in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Renal function, estimated by the glomelural filtration rate (eGFR) was assessed using the simplified Modification of Diet in Renal Disease (MDRD) formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American). Patients were divided into 5 groups according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) classification. According to this classification, stage 1 includes patients with eGFR ≥90 ml/min, while stage 2 includes patients with eGFR between 60–89 ml/min, stage 3 with eGFR between 30–59 ml/min, stage 4 with eGFR between 15–29 ml/min and stage 5 includes patients with eGFR below 15 ml/min or patients who undergo dialysis. Eighty-five patients (47%) had stage 3–5 CKD and 95 (53%) had stage 1 or 2 CKD. One half of our patients (51%) were 70 years of age or older. Advanced age (p=0.001), anemia (p<0.001), low serum albumin (p=0.017), hypercalcemia (p<0.001), elevated beta2-microglobulin (p<0.001) and Bence Jones proteinuria >2 g/day (p<0.001) were associated with stage 3–5 CKD. The majority of patients with International Scoring System (ISS)-3 myeloma had advanced renal disease (stage 3–5 CKD in 76%) in comparison with ISS-2 (33%) or ISS-1 (10.5%) patients (p<0.001). Eighty-one percent of our patients received upfront an IMiD-based therapy, while 19% received bortezomib-based regimens. The dose of lenalidomide was adjusted according to renal function. The frequency of advanced CKD was similar among patients treated with IMiDs- or bortezomib-based regimens (47% vs. 48.5%, p=0.843). Response to primary treatment was similar between patients with stage 3–5 CKD and patients with stage 1 or 2 CKD (72.6% vs. 78.7%, respectively; p=0.343). In the univariate analysis, variables associated with worse survival were: stage 3–5 CKD (median survival 39 months vs. not reached in stage 1 or 2 CKD; p=0.001), age ≥70 years (p<0.001), anemia (p=0.005), hypercalcemia (p=0.012), ISS stage (p<0.001) and LDH ≥300 IU/L (p=0.007). However, in the multivariate analysis, the presence of renal dysfunction (stage 3–5 CKD) or the degree of renal dysfunction (evaluating each CKD stage separately) was not independently associated with survival. Age >70 years (p<0.001), corrected serum calcium ≥11.5 mg/dl (p=0.04) and elevated LDH ≥300 IU/L (p=0.001) were the only independent factors associated with worse survival. The same results were obtained when we assessed renal function as a continuous variable. We also evaluated the effect of CKD staging on the survival of patients within each ISS stage and we did not find any statistically significant correlation. We conclude that the presence °r the degree of renal dysfunction has no independent prognostic impact on the survival of multiple myeloma patients who are treated upfront with novel agent-based regimens. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Haematologica ◽  
2021 ◽  
Author(s):  
Marcelo Capra ◽  
Thomas Martin ◽  
Philippe Moreau ◽  
Ross Baker ◽  
Ludek Pour ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Subgroup Analysis ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Phase 3 ◽  
New Therapies

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The Phase 3 IKEMA study (NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) vs Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

scholarly journals Impact of renal dysfunction on the management and outcome of acute heart failure: results from the French prospective, multicentre, DeFSSICA survey

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e022776 ◽  
Author(s):  
Dominique Dos Reis ◽  
Laurie Fraticelli ◽  
Adrien Bassand ◽  
Stéphane Manzo-Silberman ◽  
Nicolas Peschanski ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Acute Heart Failure ◽  
Clinical Signs ◽  
Academic Community ◽  
Close Monitoring ◽  
Early Assessment ◽  
Group 2 ◽  
Group 1

ObjectivesCardiorenal syndrome (CRS) is the combination of acute heart failure syndrome (AHF) and renal dysfunction (creatinine clearance (CrCl) ≤60 mL/min). Real-life data were used to compare the management and outcome of AHF with and without renal dysfunction.DesignProspective, multicentre.SettingTwenty-six academic, community and regional hospitals in France.Participants507 patients with AHF were assessed in two groups according to renal function: group 1 (patients with CRS (CrCl ≤60 mL/min): n=335) and group 2 (patients with AHF with normal renal function (CrCl >60 mL/min): n=172).ResultsDifferences were observed (group 1 vs group 2) at admission for the incidence of chronic heart failure (56.42% vs 47.67%), use of furosemide (60.9% vs 52.91%), insulin (15.52% vs 9.3%) and amiodarone (14.33% vs 4.65%); additionally, more patients in group 1 carried a defibrillator (4.78% vs 0%), had ≥2 hospitalisations in the last year (15.52% vs 5.81%) and were under the care of a cardiologist (72.24% vs 61.63%). Clinical signs were broadly similar in each group. Brain-type natriuretic peptide (BNP) and BNP prohormone were higher in group 1 than group 2 (1157.5 vs 534 ng/L and 5120 vs 2513 ng/mL), and more patients in group 1 were positive for troponin (58.2% vs 44.19%), had cardiomegaly (51.04% vs 37.21%) and interstitial opacities (60.3% vs 47.67%). The only difference in emergency treatment was the use of nitrates, (higher in group 1 (21.9% vs 12.21%)). In-hospital mortality and the percentage of patients still hospitalised after 30 days were similar between groups, but the median stay was longer in group 1 (8 days vs 6 days).ConclusionsRenal impairment in AHF should not limit the use of loop diuretics and/or vasodilators, but early assessment of pulmonary congestion and close monitoring of the efficacy of conventional therapies is encouraged to allow rapid and appropriate implementation of alternative therapies if necessary.

The impact of renal function on the long-term clinical course of patients who underwent percutaneous coronary intervention

2007 ◽  
Vol 69 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Michail I. Papafaklis ◽  
Katerina K. Naka ◽  
Nikos D. Papamichael ◽  
Georgios Kolios ◽  
Lampros Sioros ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Renal Function ◽  
Clinical Course ◽  
Coronary Intervention ◽  
Percutaneous Coronary ◽  
The Impact

Reversibility of Renal Failure in Newly Diagnosed Patients with Multiple Myeloma and the Role of Novel Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 955-955 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Dimitrios Christoulas ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Agent Based ◽  
Renal Response ◽  
Group A ◽  
Group B ◽  
Novel Agent

Abstract Abstract 955 Renal impairment (RI) is a common complication of multiple myeloma (MM) and is associated with increased mortality. High dose dexamethasone-based regimens have been extensively used for the initial management of patients with MM presenting with RI. Recently, novel agent-based regimens have been introduced in the frontline management of MM. The purpose of our analysis was to assess the effect of novel agent-based regimens on the rate of RI improvement and compare their efficacy with conventional chemotherapy (CC) plus dexamethasone (Dexa) in newly diagnosed MM patients. Over the last decade, 82 patients with newly diagnosed MM and RI, defined as creatinine clearance (CrCI) <50ml/min, received frontline treatment in our Center. Patients were divided into three groups: group A: 28 patients who received CC plus Dexa-based regimens (VAD, VAD-like regimens, melphalan plus Dexa); group B: 38 patients who received IMiDs-based regimens (thalidomide or lenalidomide with high dose Dexa and/or cyclophosphamide or melphalan) and group C: 16 patients who received bortezomib-based regimens with Dexa. Renal complete response (RCR) was defined as a sustained increase of baseline CrCI to >60ml/min. Renal partial response (RPR) was defined as an increase of CrCI from<15 to 30-50ml/min. Renal minor response (RMR) was defined as sustained improvement of baseline CrCI of<15ml/min to 15-29 ml/min, or, if baseline CrCI was 15-29 ml/min, improvement to 30-59 ml/min. Patients in group B were older than those of groups A and C (p=0.01) while more patient in group C had light chain only MM than in groups A and B (p=0.04). There were no significant differences in the severity of RI, Bence Jones proteinuria, hypercalcemia or ISS stage among the three groups. Improvement of renal function, recorded as RMR or better, was achieved more frequently in patients treated with novel agents (group B: 87% and in group C: 94%) than in patients treated with CC plus Dexa-based regimens (64%, p=0.024). Among 9 patients who required renal dialysis 3 became independent of this procedure after treatment. We subsequently focused our analysis in major renal responses (RPR or RCR), because this endpoint is clinically more relevant. RCR was achieved in 43% of patients in group A, in 50% in group B and in 69% of patients in group C (p=0.2) and RCR+RPR rates were 50% and 57% and 81% for groups A, B and C respectively (p=0.1). Creatinine clearance <30 ml/min was associated with a significantly lower probability of RCR or RPR only in patients treated with CC plus Dexa- or with IMiDs-based regimens (p<0.01), but not in patients treated with bortezomib (p=0.529). The probability of RPR+RCR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (p=0.619). In multivariate analysis bortezomib–based regimens (p=0.02, OR: 7, 95% CI 1.5-25) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI 2.5-22.5) were independently associated with a higher probability of RCR+RPR. The median time to RPR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (2.2 months for Group A, 1.5 months for Group B, p=0.587) but it was significantly shorter for Group C (0.7 months, p=0.017). Other factors associated with a shorter time to ≥RPR included CrCl>30 ml/min (p=0.039) and age<75 (p=0.089). In multivariate analysis bortezomib–based regimens (p=0.004, OR: 3 95% CI 1.6-6.7) and CrCl>30 ml/min (p=0.006, OR: 2.5 95% CI 1.3-4.5) were independently associated with a shorter time to ≥RPR. In landmark analysis (time was one month in order to reduce bias due to early deaths), rapid improvement of renal function (≤1 month) was associated with a trend for a longer survival compared to patients who achieved renal response later (>1 month) (47 vs. 21 months, p=0.19). Myeloma response to treatment was 58%, 68% and 79% for the three treatment groups respectively and was associated with renal response (p=0.024), though less strongly with a major renal response (p=0.061). Our data indicate that novel agent-based regimens can improve renal function in most patients; furthermore bortezomib-based regimens improve renal function to a higher degree and significantly more rapidly than CC plus Dexa-based or IMiD-based regimens even in patients with severe renal impairment. We conclude that bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients who present with renal impairment. Disclosures: Dimopoulos: JANSSEN-CILAG: Honoraria; CELGENE: Honoraria.

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