Autotransplantation in Patients with Multiple Myeloma and Concurrent Renal Failure Is Safe and Feasible and Associated with Recovery of Renal Function in > 30% of Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5126-5126
Author(s):  
Gaurav C. Parikh ◽  
Rima M. Saliba ◽  
Amit Lahoti ◽  
Chitra Hosing ◽  
Floralyn Mendoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Hazard Ratio ◽  
P Value ◽  
High Dose ◽  
Post Transplant ◽  
Relapsed Disease

Abstract Background: About 20% of patients with multiple myeloma (MM) have renal impairment at diagnosis and 2–3% are dialysis-dependent (DD). These patients may potentially benefit from high-dose therapy (HDT) and autotransplants. Method: We analyzed the outcome in 48 patient who received an autotransplant for MM while in renal failure at our institution between 8/1991 and 9/2006. Renal failure was defined as serum creatinine ≥ 2 mg/dl sustained for > 1 month. 9 patients (18%) were DD. Median age was 56 (29–72) years. 26 patients (54%) had at least a PR to induction therapy, 16 had primary refractory disease (33%) and 6 patients (12%) had relapsed disease. Median serum Cr was 2.9 mg/dl (2.0 – 12.5) and creatinine clearance (CrCl) at transplant was 33 ml/min (8.7 – 63). A CrCl of <20 ml/min was seen in 15 patients (31%). PBSC mobilization was performed with G-CSF alone in 37 patients (77%) and chemotherapy + G-CSF in the rest. Median CD34 cell dose was 4.47 x 106 /kg (1.4 – 9.7). Forty-six patients received HD melphalan as preparative regimen, while 2 patients received a combination of thiotepa, busulfan and cyclophosphamide. Results: 9 patients achieved a CR (19%), with a total response rate (CR + PR) of 67% (32 patients). 2 patients (4%) died within 100 days of autotransplant. Median times to neutrophil and platelet engraftment were 10 (9–18) and 12 (8–81) days, respectively. Grade ≥ 1 mucositis was seen in 21 patients (43%), with 3 patients (6%) experiencing grade ≥3 mucositis. After a median follow up of 34 months, the estimated median PFS and OS were 21 and 87 months, respectively. Kaplan-Meier estimates of 5-year PFS and OS probabilities were 21% and 54%, respectively. Significant improvement in renal function, defined as an increase in Glomerular Filtration Rate by 25% above baseline by 1 year post-transplant, was seen in 17 patients (35%). None of the 9 DD patients became dialysis independent. A pre-transplant creatinine level of ≥ 3mg/dl was associated with a significantly shorter overall survival (p = 0.05, HR 2.8), but did not adversely impact the improvement in renal function (p = 0.6). Conclusion: Autotransplant after HDT is safe and feasible in patients with multiple myeloma and renal failure. Response rates and outcomes were similar to those observed in other patients. Approximately 35% of patients had a significant improvement in renal function post-transplant. Analysis Results Ref= Reference N Event Free Survival Overall Survival 48 Hazard Ratio at 3 years 95% CI p value Hazard ratio at 3 years 95% CI p value Age ≤ 55 23 Ref Ref > 55 25 1.2 0.6–2.7 0.6 1.2 0.4–3.1 0.8 Cytogenetics Abnormal 10 0.9 0.4–2.5 0.9 1.7 0.5–6.1 0.4 Normal 27 Ref Ref Pretransplant Dialysis Dependent Yes 9 1.1 0.4–3.4 0.8 1.1 0.4–4.7 0.6 No 39 Ref Ref Serum Creatinine ≥ 3 23 1.6 0.7–3.4 0.2 2.8 1–7.9 0.05 <3 25 Ref Ref

Lenalidomide Plus High-Dose Dexamethasone Provides Improved Overall Survival Compared to High-Dose Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma (MM): Results of 2 Phase III Studies (MM-009, MM-010) and Subgroup Analysis of Patients with Impaired Renal Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3547-3547 ◽  
Author(s):  
Donna Weber ◽  
Michael Wang ◽  
Christine Chen ◽  
Andrew Belch ◽  
Edward A. Stadtmauer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Subgroup Analysis ◽  
Impaired Renal Function ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Duration Of Response

Abstract Lenalidomide is a novel, orally administered immunomodulatory drug (IMiD) that has single-agent activity against multiple myeloma (MM) and additive effects when combined with dexamethasone. We have previously reported improved response (OR), time to progression (TTP) and overall survival (OS) with lenalidomide-dexamethasone (Len-Dex) compared to dexamethasone-placebo (Dex) based on the results of 2 phase III trials (MM-009, North American, 353 pts; MM-010, Europe, Australia, and Israel, 351 pts). In both trials patients with relapsed or refractory MM not resistant to dexamethasone, were treated with dexamethasone 40 mg daily on days 1–4, 9–12, and 17–20 every 28 days and were randomized to receive either lenalidomide 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning at cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were also stratified with respect to B2M (≤2.5 vs. > 2.5 mg/mL), prior stem cell transplant (none vs. ≥ 1), and number of prior regimens (1 vs > 1). At a median follow-up from randomization of 17.1 mos (MM-009) and 16.5 mos (MM-010), both studies continue to show significant improvement with Len-Dex compared to Dex in OR (MM-009: 61% vs 20.5%, p<.001; MM-010: 59.1% vs. 24%, p<.001, respectively), TTP (MM-009: 11.1mos vs. 4.7mos, p<.001; MM-010: 11.3mos vs. 4.7mos, p<.001, respectively), and OS (MM-009: 29.6mos vs. 20.5mos, p<.001; MM-010: not estimable vs 20.6mos, p<.001, respectively). Pooled data from both trials demonstrates a significant improvement in duration of response for pts achieving ≥ PR with 122/216 pts (56.5%) who received Len-Dex continuing in remission (med. duration of response not reached but > 68.1 wks) compared to only 22/76 pts (28.9%) treated with dexamethasone alone (med. duration of response 22.1 wks, p<.001). An additional subgroup analysis was performed on pts with impaired creatinine clearance (cr cl). No significant difference in response rate, TTP, or OS was noted for patients with cr cl above or below 50 ml/min who were treated with Len-Dex, but for 16 pts with cr cl <30ml/min, med. TTP and OS was shorter than for those with cr cl >30ml/min, but still significantly higher than for pts treated with Dex. Grade 3–4 thrombocytopenia was significantly higher in pts with impaired renal function (<50ml/min, 13.8%; >50ml/min 4.6%, p<.01; <30ml/min, 18.8%, >30 ml/min, 5.5%, p<.05), but there was no difference for G3–4 neutropenia at either cutoff. Phase I–II evaluation to establish appropriate dosing in pts with cr cl < 30ml/min, particularly with respect to thrombocytopenia is warranted, but should not underscore improved OR, TTP, and OS for pts treated with Len-Dex regardless of creatinine clearance.

Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2739-2739 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Erasmia Psimenou ◽  
Irini Grapsa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Median Time ◽  
Objective Response ◽  
Elevated Serum ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Kinetics Of

Abstract Introduction: Renal failure is a common feature of multiple myeloma and a major management problem. There is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents, such as bortezomib, when administered to newly diagnosed or relapsed/refractory patients with renal failure. The purpose of our analysis was to assess the frequency of renal failure improvement and kinetics of serum creatinine in patients who received bortezomib-based regimens. Patients and methods: We evaluated 20 consecutive patients with newly diagnosed (n=7) or relapsed/refractory (n=13) multiple myeloma and renal failure, defined as a serum creatinine ≥ 2mg/dl. Patients’ median age was 66 years (range 43–88 years). Median serum creatinine was 3.8 mg/dl (range 2–11.9 mg/dl) and median creatinine clearance was 15.3 ml/min (range 6.4–33.3). Other features included hemoglobin <10gr/dl in 12 patients, platelets <100 × 109/l in 3 patients and elevated serum LDH in 9 patients. All patients received bortezomib plus dexamethasone alone or in combination with other agents, such as thalidomide, doxorubicin or melphalan. Reversibility of renal failure was defined as a sustained decrease of serum creatinine to <1.5 mg/dl and renal response was defined as ≥50% decrease of serum creatinine from its peak value. Results: Reversal of renal failure was documented in 35% of all patients and the median time to reversal was 23 days. Moreover, 9 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 34 days. Some decrease of creatinine was documented in 88% of patients. Among four patients who were on renal dialysis, 2 became independent of this procedure after the second and the third cycle of treatment. The objective response rate was 61% and the median progression free survival for responders was 12 months. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Grade 3–4 neutropenia and thrombocytopenia were seen in 28% and 22% of patients respectively. One patient died of infection and bortezomib had to be discontinued in 4 patients due to grade III neurotoxicity. Conclusions: When bortezomib-based regimens are administered to myeloma patients with renal impairment their toxicity and efficacy are similar to those observed in patients with normal renal function. Moreover, these regimens are associated with rapid improvement of renal function in most patients and with reversal of renal failure in one-third of them.

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.

Comparison of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study Equations and A Formula Based on Cystatin-C and Serum Creatinine for the Estimation of Glomerular Filtration Rate in Patients with Multiple Myeloma; Is It Time to Change From MDRD to CKD-EPI Equation?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5091-5091
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Efstathios Kastritis ◽  
Eirini Katodritou ◽  
Anastasia Pouli ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Serum Creatinine ◽  
Filtration Rate ◽  
Newly Diagnosed ◽  
Mdrd Equation ◽  
Ckd Stage ◽  
Stage 1

Abstract Abstract 5091 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The IMWG has recommended the use of the MDRD formula for the estimation of glomerular filtration rate (GFR) in MM patients with stabilized serum creatinine (sCr) and the classification of these patients in the 5 stages of RI, according to the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). Because MDRD equation has limitations, especially in the normal or near-normal GFR range, other prediction equations based on serum cystatin-C (cys-C), a very sensitive GFR surrogate marker, have been suggested for use in patients with CKD. Furthermore, the CKD-EPI has proposed a new formula for the estimation of GFR, which is based on age, race and sCr, and it seems to be more accurate than the MDRD equation in the estimation of GFR in CKD and in kidney transplant patients (Levey et al, Ann Intern Med 2009;150:604–12). The aim of this study was to evaluate the renal function of newly diagnosed patients with symptomatic MM using the MDRD, the CKD-EPI equations and an equation based on Cys-C/age/sCr (Stevens et al, Am J Kidney Dis 2008;51:395–406) and explore their prognostic value on survival. We studied 204 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years); 62% of patients were >65 years of age, 57% were males and 16% had sCr ≥2 mg/dl. Serum Cys-C was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum Cys-C was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, the Cys-C/age/sCr and the CKD-EPI equations were 63.95 ml/min/1.73m2, 68.08 ml/min/1.73m2 and 56.5 ml/min/1.73 m2, respectively (p<0.01 for all comparisons between equations). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 43% for MDRD vs. 42% for Cys-C/age/sCr vs. 53% for CKD-EPI (p<0.001; see also the table). Concordance for CKD stage allocation for the three equations of estimating eGFR was 68% for MDRD vs. CKD-EPI, 68% for MDRD vs. Cys-C/age/creatinine and 61% for CKD-EPI vs. Cys-C/age/sCr (see also the table). A significant correlation was found between ISS stage and MDRD, Cys/age/creatinine and CKD-EPI calculated eGFR (p<0.001 for all). The median survival for all patients was 49 months. Overall survival was significantly shorter for patients with CKD stage 3, 4 or 5, calculated by the different studied equations, compared to those with CKD stage 1 or 2 (p<0.01 for all equations). Thus, we pooled patients with CKD stages 1 and 2 and CKD stages 3–5 for survival analysis. By using the eGFR of 60 ml/min/1.73 m2 as a cut-off, patients with eGFR <60 ml/min/1.73 m2, assessed by each of the 3 studied equations, had a significantly shorter median overall survival: 24 months vs. 98 months (χ2=9.8, p=0.002) for MDRD equation, 27 months vs. 98 months (χ2=12.8, p<0.001) for Cys-C/age/sCr equation and 38 months vs. not reached (χ2=13.3, p<0.001) for CKD-EPI equation. When we adjusted for ISS stage, the allocation to RI of stage 3–5, using the CKD-EPI equation, was significantly associated with survival (p=0.041); this was not observed for the allocation to stage 3–5 RI using the other formulas (p=0.357 for MDRD equation and p=0.235 for Cys-C/age/sCr equation). Our data suggest that CKD-EPI equation for the estimation of GFR detects more MM patients with stage 3–5 RI than MDRD or Cys-C/age/sCr equations. Furthermore, CKD-EPI was the only equation that could predict for overall survival adjusted for ISS stage. The confirmation of these data may lead to the broader use of CKD-EPI formula for the evaluation of RI in patients with MM, as it has been suggested for patients with several renal disorders.Table.Evaluation of Renal Function Stage by Different EquationsCKD stageMDRD equationEquation based on Cys-C/age/sCrCKD-EPI equationp-value147 (23%)51 (25%)30 (15%)270 (34%)68 (33%)66 (32%)Friedman-test354 (26%)54 (26%)68 (33%)p<0.001422 (11%)23 (11%)23 (11)511 (5%)8 (4%)17 (8%) Disclosures: No relevant conflicts of interest to declare.

Successful Treatment of aHUS Recurrence and Arrest of Plasma Exchange Resistant TMA Post-Renal Transplantation with the Terminal Complement Inhibitor Eculizumab.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2421-2421 ◽  
Author(s):  
Daniel J Legault ◽  
Mark R Boelkins
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Transplantation ◽  
Serum Creatinine ◽  
Renal Biopsy ◽  
Thrombotic Microangiopathy ◽  
Complement Inhibitor ◽  
Post Transplant ◽  
Terminal Complement

Abstract Abstract 2421 Poster Board II-398 Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and acute renal failure (ARF). The prognosis for aHUS is poor as 25% of patients die during acute phases of the disease and 50% progress to end stage renal disease (ESRD). A high percentage of patients with aHUS experience recurrence and graft failure following renal transplantation. This report summarizes the successful use of a terminal complement inhibitor as a treatment for aHUS following renal transplant with demonstration of both clinical and pathological resolution of aHUS in a patient who was resistant to plasma therapy. A 34-year-old female with ESRD due to aHUS underwent living related renal transplantation. Approximately one month after renal transplantation, she presented with acute renal failure (ARF), with creatinine (Cr) increasing from 1.2 to 2.2 mg/dl. The renal biopsy showed thrombotic microangiopathy (TMA). ADAMTS-13 activity was normal. Tacrolimus was discontinued and corticosteroids were initiated. She responded to 14 sessions of every-other-day plasma exchange (PLEX), with stabilization of her creatinine at 1.5mg/dl. At month 5, she again presented with ARF with a renal biopsy showing TMA. PLEX was initiated once again (3 times per week) but her serum creatinine did not improve significantly during PLEX from month 5 to month 9 and ranged from 1.9 to 2.3 mg/dL with urine protein:creatinine ratio of 1.7 to 3.0. Elevations of Cr (2.34 to 3.65mg/dLl), modest elevations in LDH (209 to 380 IU/L) and ∼20% decrease in platelets (227 to 185 × 109/L) were observed when PLEX was interrupted. Diagnostic renal biopsy during this period of PLEX dependency displayed ongoing TMA. With ongoing persistent TMA despite maximal PLEX, at month 9, treatment with eculizumab, a humanized monoclonal antibody that blocks the cleavage of the terminal complement molecule C5 and generation of pro-inflammatory C5a and C5b-9, was initiated. The patient was dosed with eculizumab 900mg weekly for 4 weeks followed by 1200mg at week 5 and 1200mg every 2 weeks thereafter. After 4 weeks of induction therapy with eculizumab and no PLEX sessions, her serum creatinine stabilized at 4.0 to 4.3 mg/dL. At month 10 post transplant, and 7 weeks after the switch from PLEX to eculizumab, renal biopsy now showed no TMA and moderate residual interstitial fibrosis. Fifteen (15) months post transplant and 6 months of eculizumab treatment, the patient continues on eculizumab maintenance therapy with no requirement for PLEX. She is experiencing her best stable renal function to date, with Cr=2.7 mg/dL, a urine protein:creatinine ratio of 2.29 as well as normal platelet counts and slightly elevated LDH (∼350 IU/L) with normal haptoglobin. These results demonstrate that PLEX following recurrent aHUS post transplant did not stabilize renal function and biopsy-proven TMA persisted despite intensive PLEX therapy post transplant. In contrast, switch of PLEX to chronic terminal complement inhibitor treatment with eculizumab resolved the TMA process, stabilized and improved the transplanted kidney function, and eliminated the need for PLEX for this patient with recurrent aHUS post transplant. Clinical trials to further investigate and confirm the efficacy of eculizumab in the treatment of aHUS are ongoing. Disclosures: Legault: Alexion Pharmaceuticals: Research Funding. Off Label Use: Eculizumab, a terminal complement inhibitor, used to treat aHUS.

Thalidomide-Dexamethasone as Induction Therapy Prior to Autologous Stem-Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma and Renal Failure.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4934-4934
Author(s):  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Michela Ceccolini ◽  
Giulia Perrone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Creatinine Clearance ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 4934 Multiple myeloma (MM) patients presenting with renal feature at disease onset should not be excluded from high-dose therapy programs; seeking novel effective and non-nephrotoxic induction regimens is thus mandatory in order to maximize the reduction of tumor burden prior to transplant. From May 2002 to February 2008, 31 newly diagnosed MM patients (18 male, 13 female, median age 60 years) with symptomatic MM and renal failure, defined as creatinine clearance '50ml/min, were enrolled in a clinical trial aimed at evaluating the efficacy and the feasibility of a thalidomide-based regimen as induction therapy in preparation to autologous stem cell transplantation. Sixteen patients had a more severe renal impairment (creatinine clearance '30ml/min) and 7 of them were in chronic hemodyalisis. After informed consent, patients received four months of combined oral thalidomide (thal) (100mg/day for two weeks and 200mg/day thereafter) and dexamethasone (dex) (40mg/day on day 1-4, 9-11, 17-20/28 days on odd cycles and on day 1-4 on even cycles); peripheral blood stem cell collection was thus to be performed after priming with high-dose cyclophosphamide + G-CSF or G-CSF alone; a single or double autologous stem cell transplantation was then to follow, upon preparation with high-dose melphalan. After induction, a PR or better was obtained in 23 patients (74%), with 8 patients (26%) achieving a VGPR or better. No difference in response rate was observed in patients with a baseline creatinine clearance ≥30ml/min (86%) or < 30ml/min (62%). An improvement in renal function was more frequently observed in patients achieving ≥ PR (82% vs. 37% in patients obtaining < PR, p =0.04). Twenty-six patients underwent peripheral blood stem cell mobilization; in 17 of them (65%) the procedure was successful resulting in the collection of > 4 × 106 CD34+ cells/kg. Fifteen patients received a double autologous stem cell transplantation while a single transplant was performed in four patients. Overall, median event-free survival was 30 months, and median survival has not been reached, upon 32 months median follow-up. Toxicity profile of thal-dex was comparable to that observed in patients with a normal renal function. In conclusion, our data show that thal-dex can be safely administered in patients with newly diagnosed MM and renal failure. given the relationship between recovery of renal function and response to induction treatment, more intensive thal + bortezomib-including regimens could be potentially useful in order to rescue a higher number of patients. Disclosures Off Label Use: Thalidomide plus dexamethasone in newly diagnosed multiple myeloma.

scholarly journals Clinically Suspected Cast Nephropathy: A Retrospective, Multi-Center, Real-World Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5553-5553
Author(s):  
Agoston Gyula Szabo ◽  
Jonathan Thorsen ◽  
Charlotte Toftmann Hansen ◽  
Maja Ølholm Vase ◽  
Manuela Teodorescu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Serum Creatinine ◽  
Board Of Directors ◽  
Kidney Biopsy ◽  
Population Based ◽  
First Line ◽  
Advisory Committees ◽  
Cast Nephropathy ◽  
Initiation Of Therapy

INTRODUCTION Myeloma cast nephropathy (CN) is the most common form of monoclonal immunoglobulin-mediated kidney disease, resulting from the precipitation of excessive amounts of monoclonal serum free light chains (sFLC) and causing around 70% of the cases of dialysis-dependent renal failure in multiple myeloma (MM)(Heher et al. 2013; Nasr et al. 2012; Sanders et al. 1991). In patients with acute renal failure, the finding of a high sFLC concentration with an abnormal sFLC ratio raises the clinical suspicion of CN (Hutchison et al. 2011). Although the histopathologic diagnosis of CN is established by renal biopsy, in routine clinical practice, the diagnostic yield of this procedure is often outweighed by the urgent need of anti-myeloma treatment and the risk of procedure-related complications. Recruitment of patients with CN into clinical trials is challenging and therefore real-world data on clinically suspected CN are necessary to understand the clinical characteristics, treatment and prognosis of these patients (Bridoux et al. 2017; Hutchison et al. 2019). METHODS We searched the population-based Danish Multiple Myeloma Registry for patients diagnosed with MM according to the International Myeloma Working Group criteria between 1st of January 2013 and 31st of December 2017 with a serum creatinine concentration of 200 µg/L or higher and a sFLC concentration of 1000 mg/L or higher at diagnosis. We conducted a retrospective patient chart review in eight Danish centers and assessed baseline characteristics, biopsy results, and overall survival. Anti-myeloma treatment, sFLC levels and renal function were registered during the first 12 months after MM diagnosis. RESULTS We identified 181 patients (176 with accessible clinical records). The median age was 72 years, the median serum creatinine was 384 µg/L, the median involved sFLC concentration was 5960 mg/L and dialysis dependent renal failure was present in 35%. Pre-myeloma estimated glomerular filtration rate (eGFR) was available in 80%, the median eGFR was 66 ml/min/1.73 m2. A kidney biopsy was carried out in 21% of patients and showed CN in 70% of cases. The median time from first sFLC measurement to initiation of therapy was 4 days. The number of lines of therapy ranged between zero and six. 173 patients received one, 35 patients received two and 14 patients received three lines of therapy during the first 12 months from diagnosis. High-dose melphalan with autologous stem cell transplantation (HDT-ASCT) was carried out in 45 (26%) patients. Bortezomib was administered as part of the first-line regimen in 163 (94%) patients. The most common first-line regimens were bortezomib-dexamethasone (n=67) and cyclophosphamide-bortezomib-dexamethasone (n=46). The first line of therapy resulted in very good partial response or better in 50% (Figure 1A), but was discontinued due to death, toxicity or progressive disease in 38% of patients. Dialysis dependency, eGFR and involved sFLC concentration were assessed at the end of the first cycle, at three months, six months and 12 months after initiation of therapy. At all these time points, achievement of renal recovery was associated with the magnitude of reduction of involved sFLC (Figure 1B). The median overall survival was 3.3 years (Figure 1C). At 12 months after diagnosis, 68% of patients were alive and 15% were dialysis dependent. Reduction of the initial involved sFLC concentration to ≤ 10% at three months was strongly associated with longer OS in a multivariate cox regression analysis adjusted for age and HDT-ASCT; hazard ratio 0.42, p=0.003. CONCLUSION In conclusion, we assessed a population-based cohort of newly diagnosed MM patients presenting with a serum creatinine of 200 µg/L or higher together with a sFLC of 1000 mg/L or higher. Although CN could have been clinically suspected in these cases, a kidney biopsy was only performed in one fifth of the population. Bortezomib-based therapy was initiated quickly and resulted in deep responses in most patients. Approximately one third of patients died within a year from MM diagnosis. Achievement of early and deep reduction in involved sFLC resulted in longer OS. Figure 1 Disclosures Szabo: Janssen: Consultancy. Vangsted:Takeda: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Celgene: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Plesner:Celgene: Consultancy; AbbVie: Consultancy; Genmab: Consultancy; Oncopeptides: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding.

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.

MRD assessment using NGS in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation: Meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19002-e19002
Author(s):  
Osama Mosalem ◽  
Mahmoud Abdelsamia ◽  
Haitham Abdelhakim
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
P Value ◽  
Hematopoietic Stem

e19002 Background: The presence of measurable residual disease (MRD) preceding hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) is increasingly recognized as a risk factor for leukemic relapse and decreased survival. Over many years, attempts have been looking at developing tools to detect MRD; this includes multiparametric flow cytometry, quantitative polymerase chain reaction, and most recently, next-generation sequencing (NGS). NGS offers higher sensitivity and detection rate of disease-related gene mutations, thereby potentially improving disease outcomes. Our study sought to review the scientific literature that included NGS‐detected molecular MRD in patients with AML who underwent bone marrow transplantation. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, and SCOPUS up until October 2020. Inclusion criteria included articles that reported the association between pre-HSCT MRD detected by NGS and post HSCT outcome in patients with AML. We extracted hazard ratios for the cumulative incidence of relapse (CIR), overall survival (OS) and leukemia free survival (LFS). A random-effect model was utilized to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Results: Six studies met our inclusion criteria. Our meta-analysis showed that the detection of pre-transplant MRD by NGS was associated with increased risk of cumulative incidence of relapse (hazard ratio=2.5, CI= 1.6-3.9, with p-value <0.001) and decreased overall survival (hazard ratio=1.6, CI= 1.6-2.3, p-value 0.005). LFS was significantly higher in those who had negative MRD detection by NGS before transplantation (HR=1.9, CI= 1.3-2.8 with p-value 0.001). These results were independent of the cytogenetic risk of conditioning intensity. There was heterogeneity between our studies (I2 = 53%, 52%, and 59% for CIR, OS, and LFS, respectively). Conclusions: The application of NGS to detect MRD is a strong predictor of outcome in patients with AML who are undergoing hematopoietic stem cell transplantation. NGS-detected MRD positive status prior to HSCT is indicative of a higher risk of relapse and decreased overall survival in this meta-analysis. Despite the limitations in our study, it demonstrates the value of MRD detection by NGS in HSCT recipients.

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