scholarly journals Randomized Trial Comparing Pomalidomide, Bortezomib, and Dexamethasone (PVd) Versus Bortezomib and Dexamethasone（Vd） in NDMM with Renal Impairment（RI）

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1660-1660
Author(s):  
Jian Hou
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Group Performance ◽  
Conflicts Of Interest ◽  
Eastern Cooperative Oncology Group ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Renal Response

Abstract Background: RI is one of the most common complications of multiple myeloma (MM). The incidence of RI at diagnosis ranges from 20% to 50%, Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI, and the addition of a third drug to Vd seems to be beneficial，but not for sure. Pomalidomide is extensively metabolized by liver, with only approximately 2% of active substance eliminated in the urine, which suggests that RI may not affect pomalidomide exposure in a clinically relevant manner. The MM013(phase 2, NCT02045017) trial confirmed that Pomalidomide could be safely used in RRMM with RI and achieved good response in MM and Renal function. The OPTIMISMM (phase 3, NCT01734928) trial Subgroup analysis reported efficacy and safety of PVd vs Vd at first relapse by renal function (creatinine clearance [CrCl] < 60 vs ≥ 60 mL/min) before. The ORR significantly improved with PVd vs Vd regardless of renal status (P < .001 for both renal groups): 91.4% vs 53.6% (≥ VGPR,54.3% vs 21.4%) in the CrCl < 60 mL/min group and 89.5% vs 55.2% (≥ VGPR, 64.5% vs 23.0%) in the CrCl ≥ 60 mL/min group. Since RVd is the standard treatment for NDMM patients, We believe that standard dose Pomalidomide plus Vd will be very promising for NDMM patients with RI Study Design/ Methods: This is a multicenter, prospective, randomized phase 2 study designed to evaluate the efficacy and safety of PVd Versus Vd in Patients With NDMM and Renal Impairment（RI）. Eligible patients were aged ≥18 years and had a diagnosis of multiple myeloma, measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were required to have had no prior antimyeloma regimen. The definition of RI is based on reduced creatinine clearance (15 mL/min≤CrCl＜60 mL/min) without indication for hemodialysis, which have to be the result of myeloma. Key exclusion criteria included previous course of chemotherapy; uncontrolled malignant disorder, infection, or peripheral neuropathy, patients on dialysis will be excluded too. Approximately 79 patients will be randomized 2:1(Figure 1) to Arm A (PVd) or Arm B (Vd), both Arms will have induction therapy for 4 cycles. In Arm A, patients will receive pomalidomide 4 mg on days 1-14 of each cycle. Bortezomib 1.3 mg/m 2 on days 1, 4, 8, and 11 of each cycle. Dexamethasone 20mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (21-day cycles); In Arm B, patients will receive the same bortezomib and dexamethasone as Arm A. The primary endpoint is ≥VGPR, the secondary endpoints are MRD(-) rate,renal response,Immune function,Renal tubular function, and safety. Myeloma response and renal response will be assessed by the International Myeloma Working Group criteria after each cycle. Eficacy analyses will be performed on the intent-to-treat population; Safety analysis will be conducted in the safety population, which are composed of all patients who received ≥1 dose of study medication. The trial is currently enrolling and will be open in 8 sites in China. Disclosure：Research Sponsor : CHIATAI TIANQING PHARMACEUTICAL GROUP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Pomalidomide which was approved in RRMM will be used in NDMM with RI

Reversibility of Renal Impairment of Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Identification of Predictive Factors.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1725-1725 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Maria Gavriatopoulou ◽  
Flora Zagouri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Partial Response ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Light Chain ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Renal Response

Abstract Renal impairment (RI) is a frequent complication of multiple myeloma (MM) and a major management problem. Previous studies have shown that bortezomib is active and well tolerated in MM patients with RI and can be associated with improvement of renal function. The purpose of our analysis was to identify factors that may predict for renal impairment reversal in patients treated with bortezomib-based regimens. Over the last 5 years, 149 either newly diagnosed or relapsed/refractory MM patients received bortezomib-based regimens in our center. Our analysis is based on 46 consecutive patients with newly diagnosed (n=10) or relapsed/refractory (n=36) MM who presented with RI defined as creatinine clearance (CrCl) < 50 mL/min. Median CrCl was 23 mL/min (range 6 to 48), 34 (74%) had a CrCl<30 ml/min and 9 patients required renal dialysis. Sixteen patients (35%) had light chain only myeloma, elevated LDH>300 IU/L was found in 24%, more than 2 gr/day of Bence Jones protein in 20 (44%) and kappa to lambda free light chain ratio was ≥8 or ≤0.125 in 25%. Patients received bortezomib (B) at standard dose and schedule, plus dexamethasone (D) (16 patients, 35%), or BD in combination with other agents such as thalidomide, doxorubicin or melphalan (30 patients, 65%). Renal complete response (RCR) was defined as a sustained increase of CrCl to >60 mL/min after treatment. Renal partial response (RPR) was defined as an increase of CrCl by 50% and with improvement of renal function by at least one stage (stage IV: <30 mL/min, stage III 30–59 mL/min) but with a post treatment CrCl < 60 mL/min. RCR was documented in 22% of patients and RPR in 22% of patients. Thus, renal response (RCR + RPR) occurred in 20 patients (44%). The median time to renal response was 11 days (range 8 to 41). Among 9 patients who required dialysis 2 patients became independent of this procedure after the second cycle of treatment. The objective response rate (at least partial response) of the myeloma was 63%. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Previously untreated patients (80% vs 33% for pretreated patients, p=0.012) and those with light chain only myeloma (69% vs 30%, p=0.012) had a higher probability to achieve renal response. Response of MM to treatment was also associated with higher rate of renal response (55% vs. 24% for non-responders, p=0.037). Creatinine clearance <30 ml/min (47% vs. 33% for ClCr 330 ml/min, p=0.410), age>75 years (p=0.309), corrected serum calcium ≥10,5 mg/dl (p=0.428), Bence Jones proteinuria ≥2g/day (p=0.167) or type of bortezomib regimen (BD or BD plus other agents, p=0.222) did not significantly affect the probability of renal response. Seventeen percent of patients presenting with RI died within the first 3 months after initiation of treatment. Patients with renal response had a trend for longer survival compared to those who did not achieve a renal response (79% vs 54% alive at 1 year, p=0.150). We conclude that when bortezomib-based regimens are administered to MM patients with RI, they are associated with a clinically meaningful renal response in 44% of them. Renal response is very rapid and occurred within 2 months in all patients. Previously untreated patients and those with light chain only myeloma may have a higher probability of renal response. Moreover, patients who achieved at least a partial response of their myeloma reversed RI more frequently than non-responders. Our data were derived from an unselected patient population with severe renal failure in more than two-thirds and with 20% of patients on dialysis. They provide further evidence that bortezomib-based regimens have a unique role in patients with RI.

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.

Real-World Renal Function Among Patients with Multiple Myeloma in the United States

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Joseph Mikhael ◽  
Erin Singh ◽  
Megan Rice
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Renal Function ◽  
Combination Therapy ◽  
Renal Impairment ◽  
Drug Class ◽  
The United States ◽  
Second Line ◽  
Renal Response ◽  
Treatment Line

Background Multiple myeloma (MM) is the second most common hematologic malignancy and is associated with significant patient burden. Renal impairment has been shown to affect up to 50% of patients (pts) with MM. Renal impairment is an independent predictor of poor survival outcomes for pts with MM, with a median survival of approximately half that of pts without renal impairment. Aims To assess change in renal function by treatment line and drug class among pts with MM and renal impairment (defined as eGFR &lt;50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation [eGFR-MDRD]), and to assess real-world outcomes by baseline renal status, renal response, and drug class. Methods Using the nationwide Flatiron Health EHR-derived de-identified database based in the United States, we identified MM pts diagnosed and treated between January 2011 and November 2019 who received ≥1 line of MM therapy and had information on race. We assessed the distribution of pts by eGFR-MDRD level at the start of the first and second line of therapy and the distribution of therapy use (ie, proteasome inhibitor [PI], immunomodulatory drug [IMiD], monoclonal antibody [mAb]). We also evaluated overall survival (OS) by treatment line, stratified by eGFR at the start of each treatment line. Complete renal response (CRR) was assessed in pts with eGFR-MDRD &lt;50 mL/min/1.73 m2; using International Myeloma Working Group recommendations, responders were defined as pts with ≥1 eGFR measurement ≥60 mL/min/1.73 m2 during the treatment line. Logistic regression models were used to examine the association between treatment class and complete renal responder status adjusted for other treatment classes received, age, sex, race, practice type, year of therapy line, and cytogenetic risk. Cox proportional hazard models were used to examine OS by treatment and renal response, adjusted for other treatment classes received, age, sex, race, practice type, year of therapy line, and cytogenetic risk. Flatiron Health, Inc., did not participate in the analysis of this data. Results For the 6990 pts included in the analysis, the mean age at start of initial therapy was 68 years, 46% were female, and 17% were Black. At start of treatment lines 1 and 2, approximately 25% had eGFR-MDRD &lt;50 mL/min/1.73 m2. At treatment initiation, pts with renal impairment were older (71 vs 67 years) and were more likely to present with ISS stage III at diagnosis (38% vs 10%). Pts with renal impairment at the start of each treatment line exhibited decreased OS. Among pts with renal impairment, pts with PI use in first (adjusted odds ratio [aOR] 1.36; 95% CI, 1.04-1.77) or second line (aOR 2.09; 95% CI, 1.38-3.16) were significantly more likely to have a CRR than those without PI use. Pts with IMiD use in first (aOR 2.14; 95% CI, 1.68-2.72) and second (aOR 1.61; 95% CI, 1.10-2.36) line were significantly more likely to have a CRR than those without IMiD use. When classified by both PI and IMiD use, pts with both PI and IMiD use were significantly more likely to have a CRR than those without use of either in the first (aOR 2.35; 95% CI, 1.54-3.60) and second line (aOR 3.89; 95% CI, 1.71-8.86). Pts with PI and IMiD use as well as a CRR also had greater OS in the first (adjusted hazard ratio [aHR] 0.52; 95% CI, 0.37-0.73) and second line (aHR 0.53; 95% CI, 0.32-0.88) vs pts without either PI or IMiD use and no CRR. The use of available mAbs in line 1 or line 2 was not significantly associated with renal response. Lower mAb use, especially in earlier treatment lines, prevented further analyses by mAb combination therapies. Conclusion In this study, MM pts with renal impairment were more likely to be older and to present with ISS stage III at diagnosis. Pts with decreased renal function exhibited decreased OS compared with non-renally impaired pts. Pts who were treated with combination therapy that included PIs and IMiDs together in early treatment lines were more likely to have a CRR and OS was prolonged among these pts, highlighting the benefits of combination therapy. These data suggest that treatment inducing a renal response may result in improved outcomes. Future investigations with larger datasets may improve the understanding of the prognostic value of renal impairment and optimal combination treatment regimens for these pts. Disclosures Mikhael: Amgen, Celgene, GSK, Janssen, Karyopharm, Sanofi, Takeda: Honoraria. Singh:Sanofi-Genzyme: Current Employment. Rice:Sanofi: Current Employment.

Lenalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma; Dosing of Lenalidomide According to Renal Function and Effect On Renal Impairment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3871-3871
Author(s):  
Meletios A. Dimopoulos ◽  
Dimitrios Christoulas ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Performance Status ◽  
Prior Treatment ◽  
Renal Response ◽  
Refractory Multiple Myeloma ◽  
Dvt Prophylaxis ◽  
Grade 3 ◽  
Abnormal Renal Function

Abstract Abstract 3871 Poster Board III-807 Lenalidomide and dexamethasone (RD) is an active regimen for the management of relapsed and/or refractory multiple myeloma (MM). Over the last 2 years consecutive patients with pre-existing peripheral neuropathy grade ≥ 2 were treated with RD, regardless of their performance status and renal function. Patients with disease refractory to thalidomide, bortezomib and dexamethasone (i.e. progressive disease during treatment or within 60 days of treatment completion) were also included. Lenalidomide was administered on days 1 to 21 according to creatinine clearance (CrCl): 25 mg/day for CrCl >50 ml/min, 10mg/day for CrCl 30-50 ml/min, 15 mg every other day for CrCl 15-30 ml/min and for patients on dialysis, 15 mg three times per week on the day after dialysis. Dexamethasone was administered at a dose of 40mg PO on days 1 to 4 and 15 to 18 for the first 4 cycles and only on days 1 to 4 thereafter. RD was repeated every 28 days till disease progression or unacceptable toxicity. All patients received DVT prophylaxis with aspirin 100 mg/day unless there were already on coumadin or LMWH for pre-existing DVT or for other indications, usually atrial fibrillation. So far, 46 patients have been included and their characteristics were: median age was 69 years (range 43-87 years); median lines of prior therapy were 3 (range 1-6); prior treatment with thalidomide-containing regimens: 74% of patients (thalidomide-refractory: 68% of patients); prior treatment with bortezomib-containing regimens: 78% of patients (bortezomib-refractory: 56%); dexamethasone-refractory: 61% of patients; performance status ≥2: 33% of patients; LDH >300 IU/dl (normal value >225 IU/dl): 13% of patients; extramedullary involvement: 9% of patients; renal impairment (RI), defined as CrCl <50 ml/min: 28% of patients (range of CrCl: 13-49 ml/min). Thirty-six patients started with lenalidomide dose of 25mg/day and 10 patients with dose adjusted to renal function (10mg/day: 7 patients, 15mg every other day: 2 patients, 15 threetimes a week after dialysis: 1 patient). Response according to IMWG criteria include: CR: 17%, vgPR:5%, PR: 38%, SD: 22%, PD: 18% (PR or better: 60%). At least PR was observed in 43% of thalidomide-refractory patients, in 76% of bortezomib-refractory patients and in 20% of patients with high LDH. At least PR was documented in 60% of patients with RI and in 58% without RI. Median time to progression was 9 months and median overall survival was 16 months. Main toxicities include: neutropenia (grade 3/4): 26%; thrombocytopenia (grade 3/4): 11%; other toxicities (any grade): fatigue 50%, infections 28%, constipation 17%, diarrhea 15% and skin toxicity 11%. DVT prophylaxis with aspirin was administered to 39 patients (84%) and no patient developed DVT. Dose-reductions of lenalidomide were necessary in 46% of patients. There were no statistical differences in the incidence of adverse events in patients with normal or abnormal renal function. More specifically grade 3/4 thrombocytopenia and neutropenia occurred in 10% versus 11% (p=0.92) and 31% versus 10% (p=0.190) of patients with normal and abnormal renal function, respectively. The effect of treatment on RI reversal was also evaluated: 2 patients achieved complete renal response (i.e. baseline CrCl <50 ml/min improving to ≥60 ml/min) and 2 patients achieved minor renal response (baseline CrCl <15 ml/min improving to 15-29 ml/min or baseline CrCl 15-29 ml/min improving to 30-59 ml/min).Thus, in 4 of 10 patients with RI, treatment with RD resulted in improvement of renal function. We conclude that RD is an active treatment in patients with relapsed/refractory MM, even in patients with more heavily pretreated disease that those in the original report (Dimopoulos et al, N Engl J Med 2007;357:2123). RD is active in thalidomide and bortezomib refractory patients. With dosing of lenalidomide according to renal function, RD can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, RD may improve the renal function in a subset of patients with RI. Disclosures: Dimopoulos: CELGENE: Honoraria.

The Role of Novel Agents on Reversibility of Renal Impairment in Newly Diagnosed Patients with Multiple Myeloma; a Single Center Experience on 112 Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3961-3961
Author(s):  
Meletios A Dimopoulos ◽  
Maria Roussou ◽  
Maria Gkotzamanidou ◽  
Erasmia Psimenou ◽  
Despoina Mparmparoussi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Multivariate Analysis ◽  
Renal Impairment ◽  
Median Time ◽  
Novel Agents ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Group B

Abstract Abstract 3961 Renal impairment (RI) is a frequent complication of multiple myeloma (MM). Proteasome inhibitors and immunomodulatory drugs (IMiDs) are used as frontline therapy for MM but their effect on renal function recovery has not been clearly defined. To address this issue we studied 112 patients with newly diagnosed MM and RI who were treated in the Department of Clinical Therapeutics of the University of Athens, over the last decade. RI was defined as an estimated glomelural filtration rate (eGFR) ≤60 ml/min, using the simplified MDRD formula. Patients were divided into three groups; group T included 53 patients who received thalidomide-based regimens (with dexamethasone alone, with dexamethasone and melphalan or cyclophosphamide, or with VAD); group B included 30 patients who received bortezomib-based regimens (with dexamethasone alone, with dexamethasone and thalidomide or with cyclophosphamide) and group L included 29 patients who received lenalidomide-based regimens (with dexamethasone or with melphalan and prednisone). Lenalidomide dose was adjusted for the degree of RI according to current recommendations. Renal complete response (CRrenal) was defined as a sustained increase of baseline eGFR to >60 ml/min, renal partial response (PRrenal) as an increase of eGFR from <15 to 30–50 ml/min and renal minor response (MRrenal) as sustained improvement of baseline eGFR of <15 ml/min to 15–29 ml/min, or, if baseline eGFR was 15–29 ml/min, improvement to 30–59 ml/min. Patients in groups T and L were older than those of group B (p=0.0001). Anemia (Hb <10 g/dl) was more frequent in patients of group L (p=0.007). There were no significant differences in the severity of RI, or other clinical and laboratory parameters among the three groups. An improvement of renal function, recorded as MRrenal or better, was achieved more frequently in patients treated with bortezomib-(83%) or thalidomide-based regimens (77%) than in patients treated with lenalidomide-based regimens (55%, p=0.033). We subsequently focused our analysis in major renal responses (at least PRrenal) since this endpoint is clinically more relevant. CRrenal was achieved in 53% of patients in group T, in 70% in group B and in 34% in group L (p=0.014), while CRrenal+PRrenal rates were 55%, 80% and 38% for groups T, B and L, respectively (p=0.004). eGFR <30 ml/min was associated with a significantly lower probability of at least PRrenal (p=0.016). In multivariate analysis bortezomib-based regimens (OR: 8.8, 95% CI: 2–37, p=0.003) and thalidomide-based regimens (OR: 2.85, 95% CI: 1.01–8, p=0.046) were associated with higher probability at least PRrenal than lenalidomide-based regimens. Other factors that were independently associated with higher probability of at least PRrenal, were baseline eGFR >30 ml/min (OR: 4.85, 95% CI: 1.9–12.5, p=0.001) and age ≤65 years (OR: 3.8, 95% CI: 1.07–13.5, p=0.038). The median time to first renal response was longer for patients of group L compared to those of group T (5.5 months vs. 1.5 months, p=0.038) and it was significantly shorter for patients of group B (0.85 months, p=0.001). The median time to major renal response was 1.1 months for bortezomib-based and 2.7 months for thalidomide-based regimens, and exceeds 6 months for lenalidomide-based regimens (p=0.002). In multivariate analysis bortezomib-based regimens (OR: 3.12, 95% CI: 1.35–7.2, p=0.008) and baseline eGFR >30 ml/min (OR: 1.93, 95% CI: 1.13–3.3, p=0.015) were independently associated with a shorter time to ≥PRrenal. Myeloma response to treatment was 61%, 83% and 83% for the three treatment groups, respectively and was associated with any renal response (≥MRrenal; p=0.008) and with a major renal response (CRrenal+PRrenal; p=0.001). Among 8 patients who required dialysis (group T 4 patients, group B 4 patients), 4 patients (2 in each group) became independent of this procedure. This is the first analysis which compared the role of the three novel agents in MM patients presenting with RI. Our data indicate that novel agent-based regimens can improve renal function in the majority of patients with RI. However, bortezomib- and thalidomide-based regimens are more efficacious than lenalidomide-based regimens in this setting. Furthermore, bortezomib-based regimens act more rapidly than IMiD-based regimens even in patients with severe RI. We conclude that bortezomib-based regimens are the preferred therapy for newly diagnosed myeloma patients with RI. Disclosures: Dimopoulos: Janssen-Cilag: Honoraria; Celgene: Honoraria; Millenium: Honoraria. Terpos:Janssen-Cilag: Honoraria; Celgene: Honoraria.

Improvement in Renal Function and Its Impact on Survival in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3368-3368
Author(s):  
Wilson I Gonsalves ◽  
Nelson Leung ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
High Risk ◽  
Renal Impairment ◽  
Induction Therapy ◽  
Response To Therapy ◽  
Older Age ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Novel Agent

Abstract Background: Renal impairment is a common feature of multiple myeloma (MM) seen in over a quarter of newly diagnosed patients (pts). Studies have confirmed the presence of renal impairment (RI) as a strong predictor of inferior survival in MM. Some studies have also indicated that reversibility of RI is associated with improved survival. However, it is not clear if normalization of renal function improves the outcome to that expected for MM pts without RI at diagnosis. Methods: We evaluated 1,135 consecutive pts with newly diagnosed MM seen at the Mayo Clinic, Rochester between December 2002 and January 2011. Renal function was assessed by the estimated creatinine clearance (CrCl) which was calculated by the modified MDRD formula. We examined these pts for improvement in renal function based on their CrCl at diagnosis and their highest CrCl during their disease course. RI was defined as having a CrCl of < 60. Pts were categorized based on their renal function at diagnosis and response to therapy: Group 1- CrCl >60 at diagnosis, Group 2- CrCl <60 at diagnosis but improved to >60 after therapy and Group 3- CrCl <60 at diagnosis and remained <60 after therapy. The degree of restoration of renal function was evaluated according to the IMWG criteria. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: The median age at diagnosis was 65 years (range; 22 - 93) and 682 (60%) were male. The median follow up for the entire group from diagnosis was 73 mos (95% CI; 69 - 77). At diagnosis, 123 (11%) pts had a CrCl < 30, 322 (28%) had a CrCl of 30-59 and 690 (61%) had a CrCl >60. Most pts (N=754, 67%) received novel agent induction (NAI) therapy. The median PCLI was 0.7 (range: 0 – 22) and 91 (21%) pts had high-risk cytogenetics by FISH. The median OS for the pts with CrCl at diagnosis of < 30, 30-59 and >60 were 41 mos, 60 mos and not reached respectively (P < 0.001). Of the 445 patients with RI, the median absolute creatinine and CrCl at diagnosis were 1.6 mg/dL (range: 1 – 11) and 44 (range: 4 – 59) respectively. Among pts with RI, any improvement in CrCl was seen in 295 (66%) with median time to highest CrCl of 5 months and 228 (51%) had complete reversal of their RI. The median OS for pts with RI at diagnosis receiving and not receiving NAI therapy was not reached (NR) vs. 46 mos (P < 0.001). The median OS for Groups 1, 2 and 3 were NR, 60 and 49 mos respectively (Figure 1, P < 0.001). At a 6 month landmark analysis, the median OS for Groups 1, 2 and 3 were NR, 67 and 62 mos respectively (P < 0.001). The complete renal response and no renal response rates for pts with RI at diagnosis receiving and not receiving NAI induction therapy was (57% vs. 44%, P=0.004) and (29% vs. 39%, P=0.04) respectively. In a univariable analysis, presence of RI at diagnosis, no NAI therapy, older age, ISS stage 3, high-risk FISH, elevated PCLI, diagnosis prior to 2007 and increased LDH were found to predict for worse OS; however only older age (P<0.001), high-risk FISH (P=0.037) and lack of NAI therapy (P=0.023) retained their negative prognostic significance in a multivariable analysis. Conclusion: MM pts with RI treated with novel agent induction therapy demonstrate improved responses in their renal function and OS. The results also demonstrate improved outcome for pts with improvement in renal function, but it remains inferior to pts with normal renal function at diagnosis. These results have implications for early treatment strategies for pts at risk of developing renal insufficiency. Figure 1: OS based on improvement in CrCl upon receiving treatment Figure 1:. OS based on improvement in CrCl upon receiving treatment Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pomalidomide, Bortezomib, and Dexamethasone (PVd) for Chinese Multiple Myeloma Patients at First Relapse

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4781-4781
Author(s):  
Lugui Qiu ◽  
Gang An
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Group Performance ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Chinese Patients ◽  
Kaplan Meier ◽  
First Relapse ◽  
Grade 3

Abstract Background: The phase 3 OPTIMISMM（NCT01734928） trial done at 133 hospitals and research centres in 21 countries but no Chinese site involved in this study. In the OPTIMISMM study ,pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated excellent efficacy in patients at first relapse, including immediately after upfront lenalidomide treatment failure and other common first-line treatments, the mPFS was 20.73 months, the ORR was 90.1%, and no new safety signals were observed. Building on these promising results, we decided to explore PVd in Chinese patients at first relapse. Study Design/Methods: This is a multicenter, prospective, single-arm phase 2 study designed to evaluate the efficacy and safety of PVd in Chinese patients at first relapse. Eligible patients were aged ≥18 years and had a diagnosis of multiple myeloma, measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were required to have had only 1 prior antimyeloma regimen. Key exclusion criteria included creatinine clearance&lt;30 mL/min requiring dialysis, grade ≥3 peripheral neuropathy, or grade 2 peripheral neuropathy with pain. Patients with prior exposure to bortezomib were eligible, provided they were not refractory to a bortezomib-containing regimen dosed at 1.3 mg/m 2 twice weekly. Patient（n=62,Figure 1）will receive pomalidomide 4 mg on days 1-14 of each cycle. Bortezomib 1.3 mg/m 2 on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9 and beyond. Dexamethasone was given on days 1, 2, 4, 5, 8, 9, 11, and 12 of cycles 1-8 and on days 1, 2, 8, and 9 of cycles 9 and beyond; patients received 20 mg of dexamethasone if aged ≤75 years and 10 mg otherwise. The primary endpoint is ORR, the secondary endpoints are≥VGPR, MRD(-) rate, PFS, OS and safety. ORR will be assessed by the International Myeloma Working Group criteria after each cycle until PD. The Kaplan-Meier method will be used to estimate PFS and OS. Safety analysis will be conducted in the safety population, which are composed of all patients who received ≥1 dose of study medication. The trial is currently enrolling and will be open in 7 sites of China. Disclosures: Research Sponsor: CHIATAI TIANQING PHARMACEUTICAL GROUP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Reversibility of Renal Insufficiency in Patients with Newly Diagnosed Multiple Myeloma and the Role of different induction Regimens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5749-5749
Author(s):  
Li Bao ◽  
Jin Lu ◽  
Xiaojun Huang
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Median Survival ◽  
Conflicts Of Interest ◽  
Complete Recovery ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Renal Response ◽  
The Impact

Abstract We retrospectively compared the impact of treatments based on thalidomide, bortezomib or tranditional regimen (VAD) on renal function recovery in a consecutive, unselected population of newly diagnosed myeloma patients presenting with renal failure. Between May 2005 and February 2014, 130 (24.3%) patients with newly diagnosed multiple myeloma and RI were treated upfront with VAD or a novel agent containing regimen and all received a similar supportive care in our single center. A complete recovery of renal function(renal complete response )was observed in 56.1% of patients treated with bortezomib, in 38.9% with thalidomide and in 28.6% with VAD (P=0.033), a significant improvement of renal function (≥renalPR (renal partial response)) was observed in 63.6% of patients treated with bortezomib, in 66.1% with thalidomide and in 42.9% with VAD (P=0.162). There has a significantly difference in the rates and quality of renal response among patients with different quality of myeloma response: renal CR rates for patients who achieved ≥VGPR, PR, MR or NR were 63.1% vs 46.8% vs 35.7% vs 25.8%, P<0.05, respectively. eGFR ≥30 ml/min and myeloma response higher than PR were independently associated with a higher probability of major renal response in the multivariate analysis. The median follow-up for all patients was 36.5 months and the median survival was 74 months. The median survival for patients of groups B,T and VAD was79 months,71 months and 39 months, respectively (P=0.007). Patients died within the first 2 months from initiation of therapy and the corresponding frequencies in groups B, T and VAD were 0%, 2.8% and 17.9%, respectively (P<0.05). In multivariate analyses on survival, myeloma response higher than PR and new agents-based therapy are identified independent prognostic factors. For newly diagnosed myeloma patients with RI, bortezomib or thalidomide based regimen should be selected promptly to achieve rapid effective myeloma rate and high rates of renal recovery. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ixazomib Based Maintenance Therapy for the Patients with Newly Diagnosed Multiple Myeloma in Real-World Practice

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2718-2718
Author(s):  
Liye Zhong ◽  
Yongqiang Wei ◽  
Baohong Ping ◽  
Xin Li ◽  
Hongling Peng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Real World ◽  
Maintenance Treatment ◽  
Group Performance ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Newly Diagnosed

Abstract Background The Phase III TOURMALINE-MM4 Trial demonstrated that the oral proteasome inhibitor, Ixazomib maintenance significantly improved progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing ASCT. However, patient recruitment for clinical trials is highly selective so the extent to which study populations represent real-world patients is unclear. Currently, data validating the use of ixazomib maintenance in clinical practice in Chinese landscape is scarce. Methods we conducted a retrospective, observational study of NDMM patients meeting International Myeloma Working Group (IMWG) criteria, who received ixazomib-based maintenance therapy. Data was collected from 26 medical centers in southern China. Enrollment was stratified by risk stage, transplant status and maintenance regimens. The characteristics, toxicities and survival outcomes were recorded. Results We included 105 NDMM patients who received ixazomib-based maintenance treatment. Mean age at diagnosis was 59.82 ± 9.80 years, with 62.9% male patients. MM International Staging System (ISS), stage 3 was the most common with 49.04% of patients; 62.86% had an Eastern Cooperative Oncology Group performance score ≥2, and 81.9% with concomitant diseases. By the end of over 70 months follow-up since initial diagnosis, median PFS was 69.45 (95%CI: 31.42-107.48) months, and median OS was not achieved yet. We explored potential influencing factors of progression at the post-maintenance evaluation with a crude model using logistic regression. Difference in PFS was not statistically significant by status at pre-maintenance response, transplantation, maintenance therapy regimens (single/two/three-agent) and dexamethasone in maintenance regimens (p &gt;0.05). Eight patients (7.62%) had grade≥3 treatment-emergent adverse events (TEAEs); 5.7% discontinued treatment because of TEAEs. Common any-grade TEAEs included fatigue (18.1%), diarrhea (16.19%), and peripheral neuropathy (11.43%). Conclusion Although there are certain differences in maintenance treatment options for newly diagnosed multiple myeloma patients in real-world practice, the results of our retrospective study support that the ixazomib-based maintenance therapy was effective with acceptable toxicity and single-agent ixazomib maintenance provided enough clinical benefit compared to two or three agents. Keywords: multiple myeloma, ixazomib, maintenance therapy, real-world practice Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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