Bortezomib and Dexamethasone Therapy for Newly Diagnosed Patients With Multiple Myeloma Complicated by Renal Impairment

2009 ◽  
Vol 9 (5) ◽  
pp. 394-398 ◽  
Author(s):  
Jian Li ◽  
Dao-Bin Zhou ◽  
Li Jiao ◽  
Ming Hui Duan ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Newly Diagnosed ◽  
Dexamethasone Therapy

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.

Tubular Damage Is Ubiquitous in Newly-Diagnosed Patients with Multiple Myeloma: Comparison of Three Urinary and Two Serum Markers of Kidney Injury.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2919-2919 ◽  
Author(s):  
Meletios A Dimopoulos ◽  
Dimitrios Christoulas ◽  
Efstathios Kastritis ◽  
Maria Gkotzamanidou ◽  
Alexandra Margeli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Urinary Ngal ◽  
Newly Diagnosed ◽  
Ckd Stage ◽  
Almost All

Abstract Abstract 2919 Renal impairment is a common complication of multiple myeloma (MM). The CRAB criteria define the serum creatinine (sCr) level of >2 mg/dl as the cut-off value for starting therapy in MM patients. However, the measurement of sCr for the evaluation of renal impairment has several limitations. Furthermore, the estimation of glomerular filtration rate (GFR) by the MDRD equation has greater value in patients with stabilized sCr, while the majority of MM patients have acute renal damage, which may be irreversible. Thus, identification of individuals at higher risk of early kidney dysfunction is critical to the timely initiation of treatment to prevent permanent renal damage. For this reason, several markers of renal dysfunction have been used in renal disorders. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein overproduced by proximal tubular cells in response to kidney injury, while kidney injury molecule-1 (KIM-1) is a type 1 transmembrane glycoprotein that is overexpressed in dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Urinary NGAL and KIM-1 have never been evaluated in MM patients. To assess the value of these molecules in MM, we measured urinary and serum NGAL, urinary KIM-1, urinary and serum cystatin-C (cys-C; a sensitive marker of GFR which is not secreted in the urine) in 48 newly diagnosed symptomatic MM patients (27M/21F, median age 65 years). The estimated GFR (eGFR) was calculated using the CKD-EPI equation (proposed by the CKD Epidemiology Collaboration and is widely accepted in renal impairment). Serum and urinary NGAL was evaluated using an ELISA method (BioPorto Diagnostics A/S, Gentofte, Denmark) with a protocol applied in the Siemens Advia 1800 clinical chemistry system. Serum and urinary cys-C was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany), while urinary KIM-1 was also measured using an ELISA (R&D Systems, Minneapolis, MN, USA). For the urinary measurements, a 24h urine collection was used. Nine (19%) patients had sCr >2mg/dl, while 60% had eGFR ≥60 ml/min (CKD stages 1 & 2), 18.5% had eGFR 30–59 ml/min (CKD stage 3) and 21.5% eGFR <30 ml/min (CKD stages 4 & 5). The median values (range) for the studied markers in MM patients and in 120 healthy controls were: for urinary NGAL 36 ng/ml (0.5–2512 ng/ml) vs. 5.3 ng/ml (0.7–9.8 ng/ml), p<0.0001; for serum NGAL 162 ng/ml (53–576 ng/ml) vs. 63 ng/ml (37–106 ng/ml), p<0.0001; for urinary KIM-1 1.1 ng/ml (0.13–4.87 ng/ml) vs. 1.3 (0.1–5.3 ng/ml), p=0.345; for urinary Cys-C 0.05 mg/l (ND-13.9) vs. non-detectable, p<0.01; and for serum cys-C 1.0 mg/l (0.4–3.2 mg/l) vs. 0.7 (0.3–0.9 mg/l), p<0.01. Almost all patients (93%) had higher levels of urinary NGAL than the higher value of the controls; the respective frequency for the other markers was: 68% for serum NGAL and serum cys-C, 50% for urinary cys-C and only 10% for urinary KIM-1. All studied markers correlated with eGFR: serum cys-C (r=−0.758, p<0.001), serum NGAL (r=−0.627, p<0.001), urinary cys-C (r=−0.498, p=0.008), urinary NGAL (r=−0.430, p=0.01) and urinary KIM-1 (r=−0.369, p=0.021). Only serum cys-C strongly correlated with the involved serum free light chain (r=0.806, p<0.001). Urinary NGAL correlated also with urinary cys-C (r=0.880, p<0.001), serum NGAL (r=0.503, p=0.002), 24-h proteinuria (r=0.431, p=0.01) and ISS stage (mean±SD values for ISS-1, ISS-2 and ISS-3 were: 31±29 ng/mL, 47±52 ng/mL and 408±695 ng/mL, respectively; p=0.03). Serum cys-C correlated also with ISS stage (the values for ISS-1, ISS-2 and ISS-3 were: 0.85±0.19 mg/L, 0.94±0.24 mg/L and 2.15±0.98 mg/L, respectively; p=0.01), while urinary cys-C correlated with 24-h proteinuria (r=0.564, p<0.001). Our data suggest that almost all newly diagnosed symptomatic MM patients have tubular damage as assessed by elevated urinary NGAL suggesting that renal impairment is present very early in the disease course. Measurement of urinary NGAL and serum cys-C offers valuable information for the kidney function of MM patients and their measurement may help in the identification of patients with high risk for the development of acute renal function. The value of KIM-1 seems to be very low in myeloma reflecting the differences in the pathogenesis of myeloma-related renal dysfunction than toxic acute renal injury of other etiology. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of Serum Calcium Levels With Renal Impairment and All-cause Death in Chinese Patients With Newly Diagnosed Multiple Myeloma: A Cross-sectional, Longitudinal Study

2020 ◽  
Author(s):  
Jun Cheng ◽  
Wen Zhang ◽  
Yi Zhao ◽  
Xiayu Li ◽  
Rong Lv ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Serum Calcium ◽  
Calcium Level ◽  
Serum Calcium Level ◽  
Cox Regression ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Cross Sectional ◽  
Baseline Serum

Abstract Background: A number of studies have shown that serum calcium has a crucial role in many types of cancers. However, few studies have determined the association between serum calcium levels and renal impairment (RI) and all-cause death in Chinese patients with multiple myeloma (MM).Methods: Two hundred forty-six of 566 participants who were followed for > 6 months from a MM cohort at our institution between January 2011 and June 2017 were eligible for the retrospective study. A generalized additive model and smooth curve fitting were conducted to investigated the cross-sectional relationship between serum calcium level and RI and eGFR at baseline；Multivariate-adjusted Cox regression models were fitted to assess associations between baseline serum calcium levels and onset of end-stage renal disease(ESRD) or death in patients with MM followed for > 6 months.Results: Using the IMWG criteria,162 of 566 patients (28.6%) with newly diagnosed MM presented with RI . The mean duration of follow-up was 26.64 months. Twenty-one patients (8.54%) died and 28 patients（11.52%）had ESRD.The serum calcium level was independently associated with the occurrence of MM-related RI. There was a non-linear relationship between the serum calcium level and the presence of RI in patients with MM in the cross-sectional analysis of the baseline data. Cox regression analysis showed that baseline serum calcium levels were consistently associated with a higher risk of all-cause death after adjustment for various clinical and laboratory factors, but were not associated with the occurrence of ESRD. When patients were categorized into 2 groups according to baseline mean serum calcium level, deaths occurred in 13 patients (15.1%) with mean serum calcium level > 2.44 mmol/L compared to 8 patients (5.0%) with mean serum calcium level < 2.44 mmol/L (p < 0.05); Eighteen patients (11.46%) with a mean serum calcium level < 2.44 mmol/L progressed to ESRD compared to 13 patients (11.6%) with a serum calcium level > 2.44 mmol/L (p > 0.05).Conclusions: This observational study showed that there was a non-linear relationship between the serum calcium level and the occurrence of RI. An elevated baseline calcium level can predict all-cause death in patients with MM, but cannot predict the occurrence of ESRD, suggesting that the serum calcium level may serve as a useful clinical biomarker for the survival rate of patients with MM followed for > 6 months. Additional data from larger prospective longitudinal studies are required to validate our findings.

scholarly journals Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8096-8096 ◽  
Author(s):  
Geetika Srivastava ◽  
Vishal Rana ◽  
Martha Lacy ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Entire Cohort ◽  
Dexamethasone Therapy

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

scholarly journals Association of Serum Calcium Levels with Renal Impairment and All-Cause Death in Chinese Patients with Newly Diagnosed Multiple Myeloma: A Cross-Sectional, Longitudinal Study

2020 ◽  
Author(s):  
Jun Cheng ◽  
Wen Zhang ◽  
Yi Zhao ◽  
Xiayu Li ◽  
Rong Lv ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Serum Calcium ◽  
Calcium Level ◽  
Serum Calcium Level ◽  
Cox Regression ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Cross Sectional ◽  
Baseline Serum

Abstract Background: A number of studies have shown that serum calcium has a crucial role in many types of cancers. However, few studies have determined the association between serum calcium levels and renal impairment (RI) and all-cause death in Chinese patients with multiple myeloma (MM).Methods: Two hundred forty-six of 566 participants who were followed for > 6 months from a MM cohort at our institution between January 2011 and June 2017 were eligible for the retrospective study. A generalized additive model and smooth curve fitting were conducted to investigated the cross-sectional relationship between serum calcium level and RI and eGFR at baseline；Multivariate-adjusted Cox regression models were fitted to assess associations between baseline serum calcium levels and onset of end-stage renal disease(ESRD) or death in patients with MM followed for > 6 months.Results: Using the IMWG criteria,162 of 566 patients (28.6%) with newly diagnosed MM presented with RI . The mean duration of follow-up was 26.64 months. Twenty-one patients (8.54%) died and 28 patients（11.52%）had ESRD.The serum calcium level was independently associated with the occurrence of MM-related RI. There was a non-linear relationship between the serum calcium level and the presence of RI in patients with MM in the cross-sectional analysis of the baseline data. Cox regression analysis showed that baseline serum calcium levels were consistently associated with a higher risk of all-cause death after adjustment for various clinical and laboratory factors, but were not associated with the occurrence of ESRD. When patients were categorized into 2 groups according to baseline mean serum calcium level, deaths occurred in 13 patients (15.1%) with mean serum calcium level > 2.44 mmol/L compared to 8 patients (5.0%) with mean serum calcium level < 2.44 mmol/L (p < 0.05); Eighteen patients (11.46%) with a mean serum calcium level < 2.44 mmol/L progressed to ESRD compared to 13 patients (11.6%) with a serum calcium level > 2.44 mmol/L (p > 0.05).Conclusions: This observational study showed that there was a non-linear relationship between the serum calcium level and the occurrence of RI. An elevated baseline calcium level can predict all-cause death in patients with MM, but cannot predict the occurrence of ESRD, suggesting that the serum calcium level may serve as a useful clinical biomarker for the survival rate of patients with MM followed for > 6 months. Additional data from larger prospective longitudinal studies are required to validate our findings.

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]

Recovery of Renal Function and Independence from Dialysis in Newly Diagnosed and Relapsed Multiple Myeloma Patients - A Single Instituition Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4847-4847
Author(s):  
Girish Ravindranathan ◽  
Tanya Indrakumar ◽  
Sohail Ahmad ◽  
Moez Dungarwalla ◽  
Pamela Kanagasabapathy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Renal Impairment ◽  
Current Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Male To Female ◽  
Relapsed Myeloma

Abstract Background: Renal impairment occurs in up to 30% of patients who present with multiple myeloma and in up tp 50% of patients at some stage of the illness. It is known that renal impairment can be reversed in a significant number of such patients by correction of precipitating factors and rehydration but that 3–12% patients will require dialysis or other major intervention. These patient have a worse prognosis largely due to an excess of early deaths, renal failure being the major cause of death in 14% of myeloma patients and contributing factor in a further 14%. (Drayson et al UK MRC MM trials 1980–2002) We have conducted a study to look into the clinical course and outcome of all patients with renal impairment sufficiently severe to be referred to the regional renal unit in South East England between 2000 and 2007 with either newly diagnosed multiple myeloma (MM) or relapsed disease to try to identify features which predict for better outcomes. Methods: 62 patients with MM and renal failure received treatment in our hospital over the last 8 years. Patients have been assessed for recovery of renal function and dialysis independence in two groups - newly diagnosed (n=47) and relapsed patients (n=15). They were analysed separately as the disease tends to be biologically different at presentation and relapse, and therapeutic options may be different. In addition relatively little data on relapsed myeloma with renal failure is available. Results: 14 patients in the newly diagnosed group and 4 in the relapsed group were deemed unsuitable for an active treatment approach and have been excluded from statistical analysis in this paper but will be analysed separately to try to identify factors which could improve the outcome for this group. The patients with newly diagnosed MM and actively treated had a mean age of 65.3±1.7 years (range 41.9–83.3), male to female ratio of 1.7:1 and a mean peak creatinine at presentation of 684.5±60.9 mmol/l (range 107–1820). Light chain myeloma was overrepresented and was seen in 57.5% of patients (n=19). 12 (36.3%) of 33 the new patients avoided dialysis. 21 required dialysis, of whom 8 patients (38.1%) recovered function to dialysis independence at 6 months. There were only 3 deaths at 6 months follow-up. The mean age of the relapsed patients was 61.8±3.5 years (range 34.9–80.7), male to female ratio of 2.6:1 and a mean peak creatinine at presentation of 824±118.4 mmol/l (range 231–1591). Majority of myeloma was IgA in 36.3% (n = 4). Among the 11 relapsed, 82% (n=9) required dialysis but a significant proportion, 88% (n=8), were dialysis independent at 6 months There was only one death within 6 months of a relapse. Treatments in the 2 groups varied but involved the use of regimes containing high dose steroids in most patients. Conclusions: Our data suggest that renal failure and dialysis dependence can be avoided or is reversible in a large number of newly diagnosed and relapsed myeloma patients. This study of an unselected group of patients receiving current therapy provides an important baseline against which to compare the effect of approaches involving the newer biological agents.

Successful Treatment with Bortezomib in Combination with Bendamustine and Prednisone of Patients with Newly Diagnosed/Untreated Multiple Myeloma and Light Chain Induced Renal Failure

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2938-2938
Author(s):  
Wolfram Pönisch ◽  
Marc Andrea ◽  
Ina Wagner ◽  
Doreen Hammerschmidt ◽  
Ute Kreibich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Research Funding ◽  
Cross Resistance ◽  
Newly Diagnosed ◽  
Myeloma Protein ◽  
Increased Risk ◽  
Grade 3

Abstract Abstract 2938 Introduction: Renal impairment is one of the most severe complications of Multiple Myeloma (MM) at diagnosis. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in up to 25%. The window of opportunity to reverse renal impairment is rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as Bendamustine have turned out to be effective, rapid action drugs in the treatment of MM. Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks of DNA, and shows only partial cross resistance with other alkylating drugs. Methods: Between June 2006 and May 2011, 18 patients (median age 69; range 43 – 86 years) with newly diagnosed/untreated MM and renal insufficiency (creatinine clearance < 35 ml/min) were treated with Bendamustine 60 mg/qm day 1 and 2, Prednisone 100 mg on day 1, 2, 4, 8 and 11, and Bortezomib 1.3 mg/qm on day 1, 4, 8 and 11 (BPV). Cycles were repeated every 21 days up to the stage of maximum response or disease progression. MM response was assessed using IMWG criteria modified to include near complete response (nCR) and minimal response (MR). Eight patients were on dialysis at the time of diagnosis. Results: Fifteen patients (83%) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow up of 17 months, PFS at 12 months was 57 % and OS was 61 %. The median number of the BPV-treatment cycles was 2 (1–5) cycles. The myeloma protein decreased rapidly, reaching the best response after the first cycle in 4 patients and after the second cycle in a further 7. Six patients showed a complete remission of the kidney function (creatinine clearance > 60 ml/min) and in seven patients a partial remission (creatinine clearance > 30 ml/min) was attained. Transient grade 3 – 4 neutropenia was reported in one patient, and grade 3 – 4 thrombocytopenia occurred in 6 patients. One patient experienced a new grade 3 polyneuropathy. Summary: These results indicate that the combination of Bortezomib, Bendamustine and Prednisone is effective and tolerated in patients with newly diagnosed/untreated MM and renal failure. Disclosures: Pönisch: Mundipharma: Honoraria, Research Funding. Niederwieser:Mundipharma: Research Funding.

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