scholarly journals Clinical features and treatment outcome of elderly multiple myeloma patients with impaired renal function

2019 ◽  
Vol 33 (5) ◽  
Author(s):  
Jin Chen ◽  
Hui Liu ◽  
Lijuan Li ◽  
Zhaoyun Liu ◽  
Jia Song ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Treatment Outcome ◽  
Clinical Features ◽  
Impaired Renal Function

scholarly journals Mandibular Osteonecrosis Induced by Bisphosphonates in a Carrier of Chronicle Kidney Disease

2018 ◽  
Vol 4 (1) ◽  
pp. 1119-1125
Author(s):  
Kaohana Da Silva ◽  
Greison De Oliveira ◽  
Eleonor Garbin-Júnior ◽  
Natasha Magro-Érnica ◽  
Geraldo Griza ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Multiple Myeloma ◽  
Renal Function ◽  
Bone Resorption ◽  
Kidney Disease ◽  
Impaired Renal Function ◽  
Clinical Case ◽  
Treatment Protocol ◽  
Inorganic Pyrophosphate ◽  
Jaw Osteonecrosis

The bisphosphonates are synthetic substances of inorganic pyrophosphate that have been the basis of treatment of patients with osteolytic diseases, such as multiple myeloma, malignant hypercalcemia, Paget's disease, or patients with bone metastases. Its main pharmacological effect is inhibition of bone resorption caused by osteoclasts, which have a reduced function. Their adverse effects are infrequent but include pyrexia, impaired renal function, hypocalcemia, and more recently, maxillo-mandibular ostenecrose induced bofosfonatos. In this report we describe a clinical case of jaw osteonecrosis induced by bisphosphonates in patient with chronic kidney disease and the treatment protocol performed.

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.

Renal Safety and Pharmacokinetics of Ibandronate in Multiple Myeloma Patients With or Without Impaired Renal Function

2007 ◽  
Vol 47 (8) ◽  
pp. 942-950 ◽  
Author(s):  
Raoul Bergner ◽  
Dirk M. Henrich ◽  
Martin Hoffmann ◽  
Andrea Honecker ◽  
Gerd Mikus ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Renal Safety

scholarly journals Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Efficacy Analysis of PrE1003, a Precog Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5712-5712
Author(s):  
Joseph Mikhael ◽  
Judi Manola ◽  
Sagar Lonial ◽  
Brendan M Weiss ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Research Funding ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Phase 2 ◽  
25Mg Daily ◽  
Group A ◽  
Group B

Abstract Introduction: Lenalidomide (Len) and dexamethasone (dex) has proven to be a highly effective treatment for multiple myeloma (MM) and serves as the basis of other combinations in relapsed disease. However, nearly 1/3 of myeloma patients have renal insufficiency, and the optimal use of Len in this population is not well known. We undertook this study in 3 cohorts of pts: Group A had creatinine clearance (CrCl) of 30-60 ml/min, Group B with CrCl < 30 ml/min, and Group C, with CrCl < 30 ml/min and requiring dialysis. The Phase I component of the trial has been previously reported (ASCO 2014) demonstrating that full dose Len (25mg daily 21/28 days) can be given to all patients despite renal insufficiency, even when on dialysis. We now present data on response to treatment. Methods: In the Phase 2 component accrual was slow and the trial was terminated. However, prior to termination a modified exploratory analysis plan was established, including all 34 patients treated at the recommended phase 2 dose. This plan would declare the treatment worthy of further study if 18 or more of the 34 patients responded to treatment. This design had 84% power to distinguish a response rate of 60% from a null rate of 40%, using a 1-sided test with 10% type I error. Results: The Phase 2 efficacy cohort accrued 34 patients, consisting of 20 patients from Group A, 9 patients from Group B, and 5 patients from Group C. Response of PR or greater was seen in 17 patients, resulting in a 50% overall response rate (CI 37-63%). Treatment was well tolerated with expected adverse events; the most common adverse events were anemia, diarrhea, and fatigue. Eleven episodes of Grade 3 and one Grade 4 pneumonia were reported for 10 patients across all cohorts and dose levels; 3 were considered possibly related to treatment. Seventeen patients have remained on treatment for more than 12 cycles. In the exploratory analyses, median PFS was 7.5 months (95% CI, 3.6 - 19.7 months) and median OS was 19.7 months (95% CI, 10.4 - 42.5 months). Conclusions: Len Dex can be safely administered to patients with impaired renal function at full dose of 25mg daily 21/28 days, and is associated with a 50% response rate. Further investigation into other combinations with Len Dex in patients with renal impairment should be considered. Table Table. Disclosures Mikhael: Onyx: Research Funding; Sanofi: Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Lonial:Merck: Consultancy; Novartis: Consultancy; Onyx: Consultancy; BMS: Consultancy; Onyx: Consultancy; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Janssen: Consultancy. Weiss:Novartis: Consultancy.

A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Pre1003, a Precog LLC Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1856-1856
Author(s):  
Joseph R. Mikhael ◽  
Judith Manola ◽  
Amylou Constance Dueck ◽  
Suzanne R Hayman ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1856 Background: Lenalidomide has proven to be a highly effective treatment in relapsed multiple myeloma (MM), particularly when used in combination with dexamethasone. However, over 30% of patients with myeloma have renal insufficiency and as lenalidomide is renally excreted, little information is available about its use in myeloma patients with impaired kidney function. Defining a safe and effective dose of lenalidomide in this context is critical. Objective: We undertook this study to establish the maximum tolerated dose of lenalidomide in three cohorts of patients with different levels of impaired renal function: Group A - patients with creatinine clearance (CrCl) between 30 and 60 mL/min, Group B - patients with CrCl <30 mL/min not on dialysis, and Group C - patients with CrCl < 30mL/min who are on dialysis. Secondary endpoints included response rate, progression free survival and overall survival. Methods: Eligible patients had previously treated MM with renal impairment defined as creatinine clearance < 60 mL/min measured within 21 days prior to registration. Patients previously treated with lenalidomide were required to demonstrate clinical response (any duration) or stable disease with progression-free interval of > 6 months from start of that therapy. All patients received dexamethasone 40 mg orally on days 1, 8, 15 and 22 of a 28-day cycle. Prophylactic anticoagulation consisted of either 81 mg or 325 mg per day of aspirin. Patients also received lenalidomide orally every 1 or 2 days on days 1 through 21 of a 28-day cycle, as described below (Table 1). Starting doses were as in US Product Insert. Dose escalation follows a standard 3+3 design. Results: There have been 23 patients enrolled into groups and cohorts as shown in Table 1. Median age was 73 (range 49–89) and 13 (57%) were women. ISS stage was advanced in all patients, 0 in stage 1, 4 (18%) in stage 2 and 19 (82%) in stage 3. The regimen was well tolerated. Indeed, the MTD has not been reached in any of the groups, as no DLTs have occurred to date. The most commonly reported clinical adverse events (all grades, independent of attribution) across all patients included infections, hyperglycemia, constipation, dizziness, hyponatremia, hypocalcemia and tremor. Hematological toxicities (grade 3–4) occurred in 13 out of 21 pts (62%), mostly neutropenia and thrombocytopenia. Grade 3–4 events at least possibly related to the regimen occurred in 70% and included pneumonia (26%) and otitis media (9%). Response was seen in 14 patients, resulting in an overall response rate of 61%. CR was seen in 1 patient (4%), VGPR in 2 patients (9%), PR in 11 patients (43%), and SD for 9 patients. With median follow-up of 15.5 months, median progression-free survival is 9.8 months and median overall survival is 22 months. Conclusion: Lenalidomide and dexamethasone is a safe and effective regimen in patients with multiple myeloma and renal insufficiency. It is also very well tolerated, although cytopenias are common but manageable. MTD has yet to be reached in each group, allowing for higher doses to be given than previously thought, including 25mg daily (for 21/28 days) in patients with CrCl 30–60 mL/min, 25 mg every other day (for 21/28 days) in patients with CrCl < 30 mL/min not on dialysis, and 10mg daily (for 21/28 days) in patients with CrCl < 30 mL/min on dialysis. These results will provide needed, clinically relevant dosing for lenalidomide in MM patients with renal insufficiency. Disclosures: Kaufman: Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy.

MM-008: A Phase 1 Trial Evaluating Pharmacokinetics and Tolerability Of Pomalidomide + Low-Dose Dexamethasone In Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5393-5393 ◽  
Author(s):  
Jeffrey Matous ◽  
David S. Siegel ◽  
Hien K. Duong ◽  
Claudia Kasserra ◽  
Min Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Adverse Events ◽  
Board Of Directors ◽  
Impaired Renal Function ◽  
Low Dose ◽  
Phase 1 ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background Pomalidomide (POM) is indicated for patients (pts) with multiple myeloma who have received at least 2 prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of the last therapy. Renal impairment (RI) is a common comorbidity in multiple myeloma (MM), occurring in > 40% of pts. POM is extensively metabolized, with < 5% eliminated renally as the parent drug. Thus, renal function may not substantively affect exposure of the active parent compound. POM + low-dose dexamethasone (LoDEX) has shown efficacy in pts with relapsed/refractory MM (RRMM) with moderate RI in phase 2 and phase 3 trials. However, pts with severe RI were excluded from these trials. MM-008 is an active multicenter, open-label, phase 1 study designed to prospectively assess the pharmacokinetics (PK) and safety of POM + LoDEX in pts with RRMM and normal or severely impaired renal function. Methods Pts with RRMM and ≥ 1 prior therapy were eligible for enrollment. Pts in Cohort A (creatinine clearance [CrCL] ≥ 60 mL/min) served as the control population and received POM 4 mg on days 1-21 of each 28-day cycle. Pts in Cohort B (CrCL < 30 mL/min but not requiring dialysis) followed a standard 3 + 3 dose-escalation design, receiving POM 2 mg on days 1-21 of each 28-day cycle and based on results, escalating to 4 mg. Dosing for Cohort C (CrCL < 30 mL/min and requiring dialysis) was informed by the results from Cohort B. All cohorts received dexamethasone 40 mg (20 mg for pts aged > 75 years) on days 1, 8, 15, and 22. Pts were not permitted to enroll in more than 1 cohort. Granulocyte colony-stimulating factor for management of neutropenia was not permitted in cycle 1, but could be started on day 1 of the next cycle at the physician’s discretion. Treatment was continued until disease progression or unacceptable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (V 4.0). PK samples were obtained pre- and post-POM dose on days 1, 2, and 3 (after single doses) and days 21, 22, and 23 (after multiple doses) of cycle 1 for cohorts A and B. PK data were dose-normalized for comparison across cohorts by dividing the measured exposure by the POM dose in milligrams. Results As of April 1, 2013, 11 pts have been treated (8 in Cohort A; 3 in Cohort B at 2 mg). At screening, median age (range) was 68 years (46-71 years) and 64 years (57-64 years) while median CrCL (range) was 85 mL/min (53.1- 114.8 mL/min) and 18.4 mL/min (12.5-25.7 mL/min) in cohorts A and B, respectively. The most common grade ≥ 3 adverse events were neutropenia (Cohort A: 4 pts; Cohort B: 1 pt), infections (Cohort A: 2 pts; Cohort B: 2 pts), and anemia (Cohort A: 2 pts; Cohort B: 1 pt). No dose-limiting toxicities in cycle 1 have been reported. Median duration of treatment and relative dose intensity were similar between cohorts A and B, 4.1 months (range, 1.8-5.1 months) vs 3.9 months (range, 1.8-8.5 months) and 1.0 (range, 0.5-1.1) and 1.1 (range, 1.0-1.1), respectively. Only 1 pt (Cohort A) discontinued treatment due to adverse events. Five pts remain on study (Cohort A: 3 pts; Cohort B: 2 pts). Initial PK analyses showed that mean dose-normalized AUC024 in Cohort B was approximately 20% lower than in Cohort A. Mean dose-normalized Cmax in Cohort B was approximately 30% lower than that in Cohort A after a single dose but comparable after multiple doses. Based on these results, additional pts in Cohort B and pts in Cohort C will receive POM 4 mg. Updated PK and adverse event data will be presented at the meeting. Conclusion MM-008 is an ongoing trial prospectively evaluating the PK and safety of POM + LoDEX in pts with severe RI. Preliminary data suggest that dose-normalized exposure in pts with RRMM with severe RI is similar to that in pts with normal to mildly impaired renal function. No dose-limiting toxicities have been reported, and early tolerability data are encouraging. Disclosures: Matous: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Off Label Use: Approved in the US but not in Europe. Siegel:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Duong:Celgene: Honoraria, Research Funding. Kasserra:Celgene: Employment, Equity Ownership. Chen:Celgene: Employment, Equity Ownership. Doerr:Celgene: Employment, Equity Ownership. Sternas:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. Shah:Celgene: Consultancy, Research Funding.

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