Impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect MM Registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
Sikander Ailawadhi ◽  
Hans Chulhee Lee ◽  
Jim Omel ◽  
Kathleen Toomey ◽  
James W. Hardin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Progression Free Survival ◽  
Induction Treatment ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Front Line ◽  
Real World Data ◽  
The Impact

8518 Background: Patients (pts) with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI) are often excluded from clinical trials. Data are limited on the effects of induction treatment in these pts, who may also be ineligible for autologous stem cell transplant (SCT) due to severity of RI. This analysis investigated the impact of RVd induction on renal function in transplant eligible (TE) and noneligible (TNE) pts from the Connect MM Registry, a US, multicenter, prospective, observational study. Methods: Eligible pts were ≥ 18 y and had symptomatic MM diagnosed ≤ 2 mos prior to enrollment, as defined by the International Myeloma Working Group criteria. For this analysis, pts that received front-line RVd for ≥ 3 cycles were grouped per transplant eligibility and renal function at baseline (BL; creatinine clearance [CrCl] < 30, 30-50, > 50-80, and > 80). Pts with progressive disease at BL were excluded. Renal function at 3 mos was measured. Median unadjusted progression-free survival (PFS) was calculated from start of regimen in TE and TNE populations, with pts grouped by CrCl (≤ 60 or > 60) at BL. Results: As of 7/23/19, 421 TE and 212 TNE pts received RVd for ≥ 3 cycles. TE and TNE pts were grouped by BL CrCl of < 30 (20 and 16 pts), 30-50 (36 and 50 pts), > 50-80 (117 and 63 pts), and > 80 (248 and 83 pts). Renal function improvement was observed in all pts receiving RVd, including those with moderate (30-50 CrCl) and severe (< 30 CrCl) RI at BL (Table). In pts with > 60 CrCl and ≤ 60 CrCl at BL, median PFS in TE pts was 48.6 mos and 43.2 mos, respectively. In TNE pts, median PFS was 36.4 mos and 30.6 mos, respectively. Conclusions: The results from the Connect MM Registry indicate that pts with NDMM and RI (including moderate and severe) who receive front-line RVd for ≥ 3 cycles may see improvement in renal function at 3 mos, regardless of transplant eligibility. RVd therefore can potentially be used in pts with RI. This analysis provides real-world data that support further investigation of RVd treatment in pts with moderate or severe RI. Clinical trial information: NCT01081028 . [Table: see text]

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and &lt;VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P &lt; .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

Renal Impairment and the Use of Bisphosphonates in Patients with Multiple Myeloma: Retrospective Analysis of 114 Patients with Respect to Age and Other Clinical Characteristics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4918-4918
Author(s):  
Sam Mazj ◽  
Stuart M. Lichtman
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Renal Toxicity ◽  
Clinical Course ◽  
The Elderly ◽  
Close Monitoring ◽  
Renal Function Deterioration ◽  
The Impact

Abstract Backgound: The clinical course of multiple myeloma is often associated with significant bone related morbidity. This can be modified by the use of bisphosphonates. Studies have shown renal toxicity associated with different bisphosphonates especially following the exposure of zoledronic acid. Published literature suggests renal function deterioration occurs in 8.8–15.2% of patients at recommended dose of 4 mg infused intravenously over 15 minutes. Methods: We retrospectively reviewed the records of all patients with multiple myeloma who received bisphosphonates during the period of January 2002-June 2004 at our institution. 114 patients were analyzed (male/female 63/51; age-median 69;mean 71;range 40–92). 61 (54%) were >70 years of age. They received a total of 1301 doses (mean 11.4) during this period. The type of bisphosphonate used was: zolendronate: 58; pamidronate: 23; pamidronate changed to zolendronate (both) : 33. Patients were categorized to the type and sequence of bisphosphonates [ pamidronate vs. zoledronate and pamidronate followed by zoledronate (both) ], age and sex. Renal dysfunction was defined as an increase in serum creatinine of >0.5 mg/dl over baseline. Results: There were 19 patients (16.7%) who developed renal dysfunction. 15 of the 19 episodes (79%) occurred in the 70 years and older group. The table shows the distribution of patients, type of bisphosphonate and the distribution of patients with renal toxicity. Conclusion: This analysis showed increase in renal dysfunction occurs in all ages with use of bisphosphonates. The elderly may be particularly susceptible to this toxicity. Although we have not analyzed the impact of associated comorbidities (including type of multiple myeloma) leading to renal insufficiency in this study, the elderly patients may need more close monitoring of renal function with the use of bisphosphonates. Age and renal impairment with bisphosphonate use Age Zolendronate Pamidronate Both Total Number in paranthesis indicates the renal impairment case 40–49 6 (0) 2 (0) 2 (0) 10 (0) 50–59 10 (0) 1 (0) 4 (0) 15 (0) 60–69 14 (2) 3 (0) 11 (1) 28(3) 70–79 19 (3) 9 (1) 14 (4) 42 (8) 80+ 9 (3) 8 (0) 2 (4) 19 (7) Total 58 (9) 23 (1) 33 (9) 114 (19)

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.

Targeting Complete Response with Upfront Bortezomib Followed By Autologous Transplantation and Consolidation Therapy for Untreated Multiple Myeloma (TUBA study)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3463-3463
Author(s):  
Hideki Nakasone ◽  
Kiriko Terasako-Saito ◽  
Teiichi Hirano ◽  
Atsushi Wake ◽  
Seiichi Shimizu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Induction Treatment ◽  
High Dose ◽  
Induction Phase ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Free Survival

Abstract [Background] Multiple myeloma (MM) is generally considered incurable. Recently, novel drugs, including bortezomib, have demonstrated a survival benefit for newly diagnosed MM patients compared with classical treatments. Complete response (CR) after treatment is known to be associated with superior progression-free survival. Thus, we prospectively evaluated the efficacy and safety of boretezomib + dexamethasone (BD) for patients with newly diagnosed MM, followed by autologous hematopoietic stem cell transplantation (ASCT). We added BD consolidation therapy to aim CR if CR was not achieved after ASCT. [Patients and methods] This clinical study prospectively recruited newly diagnosed MM patients eligible for ASCT between 2010 and 2012. Due to health insurance issues in Japan, two courses of high-dose dexamethasone (HD-DX) had been administrated prior to BD induction treatment until Nov. 2011, while BD was administrated as an initial induction treatment since Dec. 2011. BD induction treatment included 1.3 mg/m2 of bortezomib on days 1, 4, 8, and 11 with 20mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. This BD induction cycle was repeated every 3 weeks for 4 courses. Thereafter, filgrastim-based mobilization and ASCT following high-dose melphalan administration was performed. If patients did not achieve CR after ASCT, BD consolidation therapy (bortezomib: 1.3 mg/m2 on days 1, 8, and 15; dexamethasone 20 mg/day on days 1-2, 8-9, and 15-16) every 4 weeks was added to target CR (Figure 1) (UMIN-CTR: UMIN000002442). [Results] The median observational duration among survivors was 1536 days (range: 464-2023) at this analysis. Of the 47 enrolled MM patients, 46 (male 27; female 19) were eligible for BD induction treatment, while the remaining one achieved CR before BD induction. The median age of the patients was 59 (range: 35-67) years. Of the 44 patients whose karyotype analyses were available, normal karyotype was observed in 35. Abnormal karyotype included complex type in 4, diploid in 1, and other abnormalities in 4. FISH revealed deletion of p53 in 5 of 39 patients whose information was available; deletion of 13-chromosome in 16 of 42, IgH-MAF fusion in 1 of 40; IgH-FGFR3 fusion in 5 of 41; IgH-BCL1 fusion in 9 of 39. Of the 46 MM patients, 19 received HD-DX prior to BD induction, and 34 received ASCT after BD induction treatment (Figure 1). During the BD induction phase, 3 patients experienced disease progression, and BD treatment was discontinued in 9 patients because of their consent withdrawal (n=2) and adverse events (n=7) including interstitial pneumonia in 2, persistent neuropathy in 1, CMV enterocolitis in 1, heart failure in 1, diabetes mellitus in 1, and liver dysfunction in 1. After BD induction phase (n=46), their response was >= CR in 4 (8%), very good partial response (VGPR) in 10 (22%), partial response (PR) in 18 (39%), stable disease (SD) in 2 (4%), and progression or withdrawal in 12 (26%). After ASCT, their response was >=CR in 9 (20%), VGPR in 11 (24%), PR in 12 (26%), SD in 1 (2%), and additional progression or withdrawal in 1 (2%). Of the 24 patients who received ASCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses (range: 1- 8). BD consolidation was discontinued in 4 patients due to persistent neuropathy or cytopenia. Finally, maximum response after ASCT with or without BD consolidation was >= CR in 19 (41%), VGPR in 7 (15%), PR in 6 (13%), < SD in 2 (2%, Figure 2). Through BD consolidation, CR was achieved in 8 of 11 patients with post-ASCT VGPR and 2 of 12 patients with post-ASCT PR. In total, 4-year progression-free survival (PFS) and overall survival (OS) was 43% (95%CI: 28-57%) and 80 % (95%CI: 64-90%), respectively. Focusing on CR patients after ASCT and those who actually received BD consolidation, PFS adjusted for karyotype and age were not different between CR patients after ASCT and after BD consolidation, while patients with VGPR or less after consolidation had significantly lower PFS (Figure 3). [Conclusion] BD induction and ASCT provided CR rate of 27% among ASCT patients, although BD induction may expectedly cause adverse events including persistent neuropathy and viral infections. Patients who achieved CR after ASCT showed good PFS, and targeting CR through BD consolidation might improve CR rate. It is worthwhile to prospectively compare the efficacy of BD consolidation only for patients who failed to achieve CR or universal consolidation strategy. Disclosures Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding.

Prognostic significance of t(11;14) expression by FISH in patients with newly diagnosed multiple myeloma in the era of novel therapies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Miguel Gonzalez Velez ◽  
Ricardo Daniel Parrondo ◽  
Tracy Andrews ◽  
Narjust Duma ◽  
Joshua Ryan Richter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Seer Data ◽  
Worse Prognosis

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

Effect of t(11;14) on outcomes of patients (pts) with newly diagnosed multiple myeloma (NDMM) in the connect MM registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8032-8032 ◽  
Author(s):  
Cristina Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
Brian G. Durie ◽  
Mohit Narang ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
Free Survival ◽  
Loss To Follow Up ◽  
Observational Cohort ◽  
The Impact ◽  
Clinical Trial Information

8032 Background: The impact of t(11;14) (16%–24% of MM pts) on prognosis is not fully understood. Consensus is lacking on the effects of induction treatment (tx) on outcomes with t(11;14). The Connect MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with NDMM designed to examine real-world diagnostic patterns, treatment (tx) patterns, clinical outcomes, and HRQoL pt-reported outcomes in pts with NDMM. The impact of t(11;14) on tx outcomes are reported. Methods: Analysis included data from pts from 250 community, academic, and government sites in cohort (C) 1 (9/2009–12/2011) and C2 (12/2012–4/2016), who completed first-line (1L; induction) tx and were tested for t(11;14) by FISH or cytogenetics. Primary end points (progression-free survival [PFS] and overall survival [OS]) were measured from start of 1L tx to earliest event (PFS, death or progression; OS, death), loss to follow-up, or data cutoff, adjusted for baseline (BL) risk factors. A sensitivity analysis excluding pts with concomitant cytogenetic abnormalities [del 17p, t(4;14), t(14;16), 1q+] was also performed. Results: By 1/2018, 3011 pts were enrolled; 2938 were treated. Of 1574 enrolled pts tested for t(11;14), 378 were t(11;14)+ and 1196 were t(11;14)−. More pts in C2 vs C1 were t(11;14)+ (60% vs 40%). BL characteristics were similar between groups. t(11;14) status did not affect PFS ( P= NS) or OS ( P= NS; Table). Pts in C1 and C2 received similar 1L txs (IMiD agent + proteasome inhibitor [PI], 30% vs 42%; PI only, 42% vs 43%; IMiD agent only, 17% vs 11%). Results were similar when pts with concomitant abnormalities were excluded. Conclusions: Results of this analysis suggest that t(11;14) does not affect PFS and OS outcomes in NDMM pts. Clinical trial information: NCT01081028. [Table: see text]

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

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.

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.

Impact of Renal Impairment (RI) on Outcomes after Treatment (Tx) with Lenalidomide and Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): First Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2112-2112
Author(s):  
Meletios A. Dimopoulos ◽  
Matthew C Cheung ◽  
Murielle Roussel ◽  
Ting Liu ◽  
Barbara Gamberi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Board Of Directors ◽  
Normal Renal Function ◽  
Research Funding ◽  
Failure Time ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Risk Of Death ◽  
The Impact

Abstract Background: Approximately 20–40% of pts with NDMM present with RI, which is associated with a negative impact on survival (Rajkumar, 2005). In the pivotal phase 3 FIRST trial (median follow-up 37 months [mos]), continuous Rd improved progression-free survival (PFS) vs. melphalan-prednisone-thalidomide (MPT) in elderly NDMM pts by 28% (25.5 vs. 20.7 mos; HR = 0.72; P < 0.01) (Facon, Blood 2013). Although 121 pts receiving continuous Rd are still on Tx, the interim overall survival (OS) analysis showed a 22% reduction in the risk of death in favor of continuous Rd vs. MPT (HR = 0.78; P = 0.02). The present analysis was conducted to determine the impact of RI on PFS, OS, and time to 2nd antimyeloma Tx (AMT) as clinical study outcomes. Methods: Pts were randomized to 3 Tx arms: continuous Rd until progression (n = 535); Rd for 18 cycles (72 weeks) (Rd18; n = 541); or MPT for 12 cycles (72 weeks) (n = 547). Enrolled NDMM pts were categorized according to their renal function: 24% had normal renal function (creatinine clearance [CrCl] ≥ 80 mL/min), 44% presented with mild RI (≥ 50 and < 80 mL/min), 23% had moderate RI (≥ 30 and < 50 mL/min), and 9% had severe RI (< 30 mL/min). Pts requiring dialysis were excluded. Lenalidomide starting dose was 25 mg QD for pts with normal renal function or mild RI, 10 mg QD for moderate RI, and 15 mg QOD for severe RI. Melphalan dose was reduced by 50% in pts with moderate or severe RI. The primary endpoint was PFS (continuous Rd vs. MPT); secondary endpoints were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety, and improvement in renal function from baseline. Improvement in RI was defined as shifts from baseline to most extreme post-baseline value of the calculated CrCl as a measure of renal function during the active Tx (N = 1484). Results: A PFS benefit favored continuous Rd vs. MPT irrespective of the degree of renal function (Table 1): there was a benefit in pts with normal renal function (HR = 0.72 (0.51–1.02); P = 0.06), and better in pts with mild RI (HR = 0.79 (0.62–1.00); P = 0.05) and moderate RI (HR = 0.62 (0.45–0.85); P < 0.01). A PFS benefit was also seen with continuous Rd vs. Rd18 (a secondary comparison) in pts with mild RI and moderate RI (P < 0.01 for both). An interim OS benefit with continuous Rd vs. MPT was observed in most renal subgroups. Similar results were observed between Rd18 and MPT in terms of PFS or interim OS in any of the renal subgroups. Continuous Rd, compared with Rd18 or MPT, extended time to 2nd AMT in most renal groups except severe RI (CrCl < 30mL/min) (Table 2). Improvement in RI was observed more frequently in pts treated with continuous Rd than those with Rd18 or MPT: improvement of mild RI, 48%, 43%, and 48%, respectively; of moderate RI, 67% 61%, and 62%; and of severe RI, 64%, 59%, and 56%. Overall, < 5% of pts in any Tx group experienced a worsening in renal function status during Tx (continuous Rd 2.2%; Rd18 2.8%; MPT 2.7%). The most common grade 3–4 adverse events (AEs) for these Txs were anemia, neutropenia, thrombocytopenia, deep-vein thrombosis/pulmonary embolism (DVT/PE), and peripheral sensory neuropathy (Table 3). Tx discontinuation due to AEs increased in pts with moderate and severe RI, regardless of the type of Tx (Table 3). Conclusions: PFS, OS (at interim analysis), and time to 2nd AMT outcomes generally improved continuous Rd vs. Rd18 or MPT in transplant-ineligible NDMM pts with normal renal function, and in those with mild or moderate RI. The small number of pts in the severe RI group precluded a meaningful conclusion. Continuous Rd was generally well tolerated and renal function improved in the majority of pts during Tx with continuous Rd vs. Rd18 or MPT. Disclosures Dimopoulos: Celgene Corporation: Consultancy, Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Roussel:Celgene: Consultancy, Lecture fees Other, Research Funding. van der Jagt:Celgene Corporation: Research Funding. Jaccard:Celgene Corporation: Honoraria, Research Funding. Tosikyan:Celgene: Consultancy. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bensinger:Celgene Corporation: Consultancy, Research Funding. Schots:Celgene: Research Funding. Chen:Celgene Corporation: Employment. Marek:Celgene Corporation: Employment, Equity Ownership. Ervin-Haynes:Celgene Corporation: Employment. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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