The efficacy and safety of lenalidomide in multiple myeloma with severe renal impairment

2015 ◽  
Vol 15 ◽  
pp. e310
Author(s):  
K.S. Jung ◽  
H.-N. Song ◽  
K.H. Yoo ◽  
J.Y. Lee ◽  
S.H. Lim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Efficacy And Safety

scholarly journals Efficacy and Safety of Melphalan 140mg/m2 Conditioned Autologous Stem Cell Transplantation in Elderly Pre-Dialysis and Dialysis Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5822-5822
Author(s):  
Hatem Ali ◽  
Baharani Jyoti ◽  
Shankaranarayana Paneesha ◽  
Richard Lovell ◽  
Alex George Kanellopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Renal Impairment ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Severe Renal Impairment ◽  
Efficacy And Safety ◽  
Dialysis Patients ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Information is currently available for the efficacy and safety of autologous stem cell transplantation (ASCT) conditioned with melphalan in multiple myeloma patients with mild to moderate chronic kidney disease. However, little information is available on ASCT in patients with severe renal impairment or those on dialysis with multiple myeloma. This population is usually not considered for ASCT due to a high risk of mortality. One retrospective study provides data on ASCT conditioned mainly with 200mg/m2 melphalan with high treatment related mortality (TRM) at 15%. Here we present safety and efficacy data on dose reduced melphalan (140/m2) conditioned ASCT in patients with severe renal impairment or haemodialysis at the time of transplant with a TRM of 0%. Patients and methods: We identified and report on 10 ASCT procedures carried out on 9 (7 males and 2 females) myeloma patients with a glomerular filtration rate (eGFR) of 35 ml/min/1.73m2 or less between 2006 and 2016. Median age was 58(51-74) years. Five patients were on haemodialysis at diagnosis and 4 went into ASCT while on haemodialysis. Six patients had light chain multiple myeloma. Initial therapy was bortezomib based in 6 patients, with 4 receiving thalidomide and 1 received both thalidomide and bortezomib pre ASCT. Most patients were mobilised with G-CSF alone and only 1 received cyclophosphamide and G-CSF. ASCT was conditioned in all cases with 140mg/m2of Melphalan. Patients on hemofiltration were supported during ASCT as per institutional guidelines. We collected data on response, stem cell collection, engraftment, progression free survival (PFS), overall survival (OS) and treatment related mortality (TRM). Results: Median follow up for the whole group was 24 (6-114) months. Pre ASCT 6 patients were in VGPR and 3 in PR. The median cell dose collected was 6.92×10 6 CD34 cells/kg (range 3.06-8.27). The median time to neutrophil engraftment (absolute neutrophil count>0.5×109/L) and platelet engraftment (>20×109/L) was at day 13 and 15 respectively. The TRM at day+100 was 0%. Post ASCT best responses were as follows-7 patients were in VGPR; 1 in PR and 1 progressed. The median PFS was 24months and median OS was 27 months. At the time of data collection only one person had died. The cause of death was disease progression with refractory disease. One patient became free of haemodialysis pre ASCT, one after ASCT and 1 more dropped frequency of dialysis sessions from 3 to 2 per week. Discussion: Autologous stem cell transplant using low dose Melphalan (140mg/m2) as consolidation post a bortezomib based induction therapy is an effective and safe treatment option for the pre-dialysis and dialysis patients with multiple myeloma. In our hands the TRM is extremely low suggesting the lower dose to be more appropriate than melphalan at 200mg/m2. It provides good PFS and in some cases freedom from haemodialysis. Further prospective trials are needed to confirm these findings. Disclosures Paneesha: Abvie: Honoraria. Kishore:celgene: Other: travel grant.

Pomalidomide, bortezomib, and dexamethasone (PVd) in lenalidomide (LEN)-pretreated relapsed refractory multiple myeloma: Subanalysis of patients with renal impairment in OPTIMISMM.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20562-e20562
Author(s):  
Fredrik Schjesvold ◽  
Meletios A. Dimopoulos ◽  
Meral Beksac ◽  
Albert Oriol ◽  
Jindriska Lindsay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Depth Of Response ◽  
Common Grade ◽  
First Relapse ◽  
Grade 3 ◽  
Line Of Therapy

e20562 Background: Upfront LEN until disease progression is a standard treatment (Tx) in multiple myeloma (MM). Data are limited on optimal Tx after first-line LEN, especially in LEN-refractory patients (pts), a growing population. In OPTIMISMM (phase 3, NCT01734928), PVd significantly improved median PFS at first relapse in relapsed refractory MM (RRMM) pts, of whom 100% were LEN pretreated and 57% were LEN refractory (median, 20.7 vs 11.6 mos; HR = 0.54 [95% CI, 0.36-0.82]; P = .0027) vs Vd (Richardson, 2019). Pd has shown efficacy and safety in RRMM pts with moderate or severe renal impairment (RI), including those on dialysis (Dimopoulos, 2018). However, outcomes with second-line PVd in RRMM pts with RI have not been assessed. Here we report efficacy and safety of PVd vs Vd at first relapse by renal status (CrCl < 60 vs ≥ 60 mL/min). Methods: Pts received PVd or Vd (1:1) in 21-day (D) cycles (C); POM 4 mg/D on D1-14 (PVd arm only); BORT 1.3 mg/m2 on D1, 4, 8, 11 of C1-8 and on D1, 8 of C9+; and DEX 20 mg/D (10 mg/D for pts aged > 75 yrs) on days of and after BORT. Pts on dialysis were excluded. Results: Of 559 pts enrolled, 226 (40%) had 1 prior line of therapy; of whom 28% had CrCl < 60 mL/min and 4% had severe RI (CrCl < 30 mL/min). In pts with CrCl < 60 mL/min (PVd vs Vd), median age was 74 vs 73 yrs. In pts with CrCl ≥ 60 mL/min (PVd vs Vd), median age was 62 vs 64 yrs. A higher proportion of pts with baseline CrCl < 60 (23% vs 43%) than ≥ 60 mL/min (7% vs 8%) had ISS stage III at study entry. Data cutoff was Oct 26, 2017. Median PFS was improved with PVd in both renal groups (Table). ORR significantly improved regardless of renal status. Depth of response also improved with PVd vs Vd; ≥ VGPR occurred in 54% vs 21% in the CrCl < 60 mL/min group and 64% vs 23% in the CrCl ≥ 60 mL/min group. Myelosuppression was the most common grade 3/4 TEAE (Table). Conclusions: Second-line PVd led to improved vs Vd in pts with RRMM and RI; however, the PFS difference was not statistically significant. Safety was consistent for PVd with no new signals in pts with RI. These findings further support the earlier use of POM-based Tx in RRMM pts, including those with mild to moderate RI. Clinical trial information: NCT01734928. [Table: see text]

Lenalidomide Is Effective Treating Patients With Relapsed Multiple Myeloma and Very Severe Renal Impairment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5401-5401
Author(s):  
Cristina M. Joao ◽  
Fernando Gomes ◽  
Catarina Geraldes ◽  
Joana Maria Parreira ◽  
Manuel L Neves ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Dose Adjustment ◽  
Board Member ◽  
Severe Renal Impairment ◽  
Response Duration ◽  
Advisory Board ◽  
Second Primary ◽  
Primary Tumors ◽  
Second Primary Tumors

Abstract Introduction Patients with multiple myeloma (MM) and severe renal impairment (SRI) have shorter survival and are often excluded from clinical trials. In these patients the use of Lenalidomide (Len) is based in pharmacokinetic models and because of the risk of increased toxicity, Len dose must be adjusted to renal function. Purpose To evaluate the outcomes of relapsed MM patients (RMM) with SRI (baseline creatinine clearance (CrCl) <30ml/min) treated with Lenalidomide-dexamethasone (Lendex), including patients under hemodyalisis. Methods We conducted a retrospective multicenter study in four Portuguese referral hospitals. All consecutive patients with RMM and SRI treated with Lendex between January 2007 and December 2012 were included. Lendex treatment was considered as the administration of low doses of dexamethasone and Len doses between 25mg/d and 5mg every other day. We evaluated the efficacy (response rate (RR), response duration and impact on renal function) and the relevant toxicities (myelo and neurotoxicity, thrombotic and infectious complications and second primary tumors). Results We retrospectively analyzed 22 patients with SRI and RMM treated with Lendex (median CrCl at start of Lendex was 19 ml/min with 13 patients under dialysis): 55% males; median age at diagnosis 63yo; median age at start of Lendex 68yo (51-79); main subtypes were IgGk (45%) and IgGλ (18%); 3 patients with high-risk cytogenetics; 5 plasmocytomas; 1 amyloidosis; 77% received Lenalidomide ≤10mg/d x 21 days in monthly cycles; median 8 cycles (2-50). Median number of previous lines was 2 (1-6). The global RR was 72% (16/22; 12 patients with ≥PR); 6 pts had progressive disease. Five out of 6 (83%) of the patients who progressed with Lendex had prior exposure to thalidomide. Median follow-up from start of Lendex was 14 months (2 – 62). The median time until maximal response was 3 months and the median response duration was 31 months (5 – 55) and in 58% (7/12) the response was longer than 2 years. Eighteen percent had renal improvement (median CrCl improvement of 44ml/min) but all the 13 patients on hemodyalisis maintained the need for this treatment. The treatment was interrupted in 3 cases because of adverse events and all the patients were on thromboprophylaxis with aspirin. In the long-term responders a continuous Len dose adjustment was required mainly because of myelo and neurotoxicity and the dexamethasone dose was reduced according to toxicities (metabolic, fatigue and psychiatric effects). There were no critical infections or second primary tumors. Conclusions CrCl<60 ml/min is a cut-off for Lenalidomide dose reduction. In our experience, after initial dose-adjustment of therapy, there should be a continuous process of dose-adjustment taking into account the individual tolerance, even without additional renal impairment. Lendex dosing adjusted according to CrCl does not negatively impact response or the rate of side effects. It may also have a potential to reverse RI and induce long duration of response. We concluded that Lendex is an effective and safe treatment regimen for relapsed MM patients with severe renal insufficiency. Disclosures: Joao: yassen: member of advisory board, member of advisory board Other; Celgene: member of advisory board, member of advisory board Other. Esteves:Celgene: member of advisory board, member of advisory board Other; Yassen: member of advisory board, member of advisory board Other.

scholarly journals The Efficacy and Safety of Sofosbuvir/Daclatasvir Fixed-Dose Combination in Iranian Hemodialysis Patients with Hepatitis C Virus Infection

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Kasra Ghanaat ◽  
Heidar Sharafi ◽  
Seyed Moayed Alavian
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Hemodialysis Patients ◽  
Virologic Response ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Patient Reported

Background: Although several regimens have been approved for the treatment of hepatitis C virus (HCV) infection, sofosbuvir-based regimens are not approved for the treatment of HCV infection in patients with severe renal impairment. Methods: This study was conducted on 51 hemodialysis patients infected with HCV. The patients received a constant dose of sofosbuvir/daclatasvir (SOF/DCV). Sustained virologic response (SVR) was evaluated 12 weeks after completion of treatment. The subjects were selected and treated with a combination of SOF/DCV. Eleven patients expired during the anti-HCV treatment due to causes not related to liver disease or antiviral therapy. Results: Finally, 40 patients finished the treatment, and 36 cases were evaluated for SVR. Among those tested for SVR, 35 (97.2%, 95% CI: 85.5 - 99.9%) achieved SVR and one (2.8%, 95% CI: 0.1 - 14.5%) relapsed. No patient reported severe adverse events. Conclusions: The combination of SOF/DCV showed great efficacy and safety in hemodialysis patients with severe renal impairment and chronic HCV infection.

scholarly journals Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update

2018 ◽  
Vol 36 (8) ◽  
pp. 812-818 ◽  
Author(s):  
Kenneth Anderson ◽  
Nofisat Ismaila ◽  
Patrick J. Flynn ◽  
Susan Halabi ◽  
Sundar Jagannath ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Zoledronic Acid ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Plain Radiograph ◽  
Compression Fracture ◽  
Hematologic Malignancies ◽  
Cochrane Library

Purpose To update guideline recommendations on the role of bone-modifying agents in multiple myeloma. Methods An update panel conducted a targeted systematic literature review by searching PubMed and the Cochrane Library for randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies. Results Thirty-five relevant studies were identified, and updated evidence supports the current recommendations. Recommendations For patients with active symptomatic multiple myeloma that requires systemic therapy with or without evidence of lytic destruction of bone or compression fracture of the spine from osteopenia on plain radiograph(s) or other imaging studies, intravenous administration of pamidronate 90 mg over at least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks is recommended. Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative. Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting. The update panel recommends that clinicians consider reducing the initial pamidronate dose in patients with preexisting renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The update panel suggests that bone-modifying treatment continue for up to 2 years. Less frequent dosing has been evaluated and should be considered in patients with responsive or stable disease. Continuous use is at the discretion of the treating physician and the risk of ongoing skeletal morbidity. Retreatment should be initiated at the time of disease relapse. The update panel discusses measures regarding osteonecrosis of the jaw. Additional information is available at www.asco.org/hematologic-malignancies-guidelines and www.asco.org/guidelineswiki .

Integrative assessment of the effect of renal function on ribociclib treatment and dose recommendation in advanced breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13037-e13037
Author(s):  
Yan Ji ◽  
Vitaly Yartsev ◽  
Yingbo Wang ◽  
Michelle Quinlan ◽  
Paolo Serra ◽  
...  
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Phase 1 ◽  
Moderate Renal Impairment ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Integrative Assessment

e13037 Background: Ribociclib is an orally administered CDK4/6 inhibitor used in combination with endocrine therapy (ET) to treat women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative advanced breast cancer (ABC). An integrative assessment was conducted to evaluate the effect of renal function on the pharmacokinetics (PK), efficacy and safety of ribociclib. Methods: To assess the effect of mild and moderate renal impairment, a subgroup analysis was performed to evaluate PK parameters of ribociclib following oral administration of 600 mg QD 3 weeks on/1 week off in two Phase 1/2 and one Phase 3 clinical trials. Steady-state PK exposures in ABC patients at the 600 mg dose was estimated by a population PK model developed based on a pooled dataset from five Phase 1 to 3 trials and were compared by renal function. Efficacy and safety were also analyzed by renal function in a Phase 2 and three Phase 3 trials in ABC patients. The effect of severe renal impairment on ribociclib PK was assessed in a Phase I study in non-cancer subjects following a single oral 400 mg dose. Results: PK analyses in cancer patients showed that both single-dose and steady-state exposure of ribociclib at the 600 mg dose in patients with mild or moderate renal impairment were comparable to patients with normal renal function. Estimated steady-state PK exposure in patients with mild or moderate renal impairment is also comparable to patients with normal renal function. The primary efficacy results of progression free survival (PFS) and the safety profiles were comparable across renal-function cohorts in ABC patients. In non-cancer subjects administered a single oral dose of 400 mg, ribociclib AUCinf and Cmax increased 2.67- and 2.30-fold in subjects with severe renal impairment, respectively, compared to subjects with normal renal function. Conclusions: PK, efficacy and safety of ribociclib are consistent across patients with normal renal function, mild or moderate renal impairment. Hence, no dose adjustment is required in mild or moderate renal impaired patients. Severe renal impaired patients are recommended to have a reduced dose based on PK data in non-cancer subjects.

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