scholarly journals Racial Disparity in Patients with Multiple Myeloma Are Blunted in the Era Novel Therapies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2525-2525
Author(s):  
Leon Bernal-Mizrachi ◽  
Ajay K Nooka ◽  
Chandra Pooja ◽  
Monica S Chatwal ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Factors Associated ◽  
Indolent Disease ◽  
The Impact ◽  
White Patients

Abstract Background: Multiple myeloma is the most common hematological malignancy among african americans (AA). Prior studies have shown conflicting results for outcomes based upon ethnicity following autologous stem cell transplantation (ASCT). However, much of this data is older, and predates the use of novel agents such as bortezomib (V), lenalidomide (R) and thalidomide (T). Methodology: We performed a retrospective analysis of 292 patients (147 AA and 145 Caucasian) treated with novel agents (proteasome inhibitors or immune modulators) and ASCT from 2006 to 2012 at the Winship Cancer Institute of Emory University to evaluate the impact of ethnicity on outcomes. Results: Baseline characteristics such as stage (International Staging System, ISS), presence of lytic lesions or plasmacytomas, immunoglobulin subtype, and cytogenetic risk category at presentation, were comparable between AA and white patients. Among AA, 112 (76.19%) patients received bortezomib containing regimens (VRD: 34.8%, VTD: 22.3%, VDTPACE:11%, VDD:10%, VD:19% and others bortezomib regimens 8%), 54 (36.7%) patients received lenalidomide (VRD: 34.8% or RD: 11.6%) and 72 (49%) patients received thalidomide (VTD: 22.3% or TD: 11.6%). In white patients 113 (77.93%) received bortezomib containing regimens (VRD: 33.1%, VTD: 17.2%, VDTPACE:9.6%, VDD: 1.4% and VD:11.7% and other bortezomib regimens 1.3%), 69 (47.6%) patients received lenalidomide containing regimens (VRD:33.1% and RD:11%) and 62 (42.8%) patients received thalidomide containing regimens (VTD: 17.2% or TD: 15%). A higher percentage of patients in the white cohort carried the antecedent diagnosis of monoclonal gammopathy in white patients (AA:0 vs white: 4.8%, p=0.007), and as expected, AA patients presented at a younger age when compared with whites (mean age of 55 vs 59 years, respectively, p<0.001). The overall response rate (ORR) of induction in the entire population was 86%, with an >VGPR of 58.8%. No difference was identified in pre-transplant ORR and >VGPR between AA (87.9% and 25.9%, respectively) and white patients (81.54% and 22.4%, respectively, p>0.1). Similarly, the ORR and >VGPR 100 days after transplantation was comparable between both ethnic groups (AA: OR:90.74% and >VGPR:74.07% vs white OR:90.65% and >VGPR: 77.57%, p>0.1). The depth of response after ASCT improved similarly in both groups (AA: 57.3% vs white: 67.7%, p=0.1). When the overall survival and progression free survival where evaluated, we found no significant differences between both cohorts. Factors associated with longer PFS in the population studied include AA race and the introduction of lenalidomide in the induction regimen. In AA patients univariate analysis identified early stage at presentation, indolent disease (prolong time from diagnosis to transplant), optimal pre-transplant response, and pre-transplant use of lenalidomide (HR:0.38 (0.18-0.8), p=0.01) as factors that potentially prolong PFS. Multivariate analysis identified the use of lenalidomide, as part of the pretransplant regimen, to reduce the risk of relapse (HR:0.38 (0.18-0.8), p=0.01) compared to bortezomib use (HR: 5.3 (2.11-11.98), p<0.001). In white patients, univariate and multivariate analysis identified that IgG and kappa light chain MM and indolent disease were factors associated with longer PFS, while history of plasma cell leukemia was related to shorter PFS. In conclusion, our results showed that novel agents have improved the response rate of both ethnic populations. From our preliminary analysis, it appears the PFS is longer among AA patients, suggesting a potential difference in MM biology of this patient population. Disclosures Lonial: Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

Multiple Myeloma Multicenter Registry in Colombia: The Impact of Autologous Stem Transplantation on Overall and Disease-Free Survival

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Virginia Abello ◽  
Claudia Lucia Sossa ◽  
Henry Idrobo ◽  
Guillermo Quintero ◽  
William Mantilla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Entire Group ◽  
Hematologic Neoplasms ◽  
First Line ◽  
Free Survival ◽  
The Impact

Aim: RENEHOC (Registro Epidemiológico de Neoplasias Hematológicas en Colombia) is a multicenter clinical quality database established in January 2018. The primary aim of the database is to provide local information on diagnosis and treatment of Multiple Myeloma (MM) and other hematologic neoplasms; this is key to show authorities the improvements that must be made to achieve better outcomes for Colombian patients and pose research questions relevant to our population. The aim of this report is to analyze variables related to event free survival (EFS) and overall survival (OS) in MM Colombian patients. Study population: An ambispective registry of adult MM patients, treated in approved centers over the last 10 years in Colombia. As of July 2020, 890 patients have been registered. Descriptive statistics were used for patient's demographic and clinical characteristics. The Kaplan-Meier method was used to assess DFS and OS. Hazard Ratios (HR) using Cox proportional hazards regression modeling was estimated. &lt;65 yrs. patients were considered transplant eligible (TE) and older than 65 yrs. transplant ineligible (TI). Results: Data from 890 MM patients were reviewed. Median age at diagnosis was 66.8 (SD 11.17) years (TE 57 yrs., SD 6.71; TI 74.8 yrs., SD 6.87); 398 (57%) were TE; 52.9% were male. At diagnosis median hemoglobin was 10.1 (SD 2.5), 242 (27.2%) had renal failure, and 379 (42.6%) pathological fractures. IgG was the most common M component (n=328, 36.8%). Most patients were in an advanced stage by Durie Salmon at diagnosis (DS IIIA or IIIB: n=523, 77.4%), and had high risk ISS (ISS 1: n=128, 20.6%; ISS 2: n=180, 29.0%; ISS 3: n=312, 50.3%; NA n=270). Only 17,9% (n=160) had cytogenetic prognostic characterization. There were not significant differences in clinical characteristics at diagnosis between TE and TI patients. The most common induction regimen for TE were Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) (n=190, 49%) and Bortezomib-Thalidomide-Dexamethasone (VTD) (n=103, 27%). For TI patients, most common regimens in first line were CyBorD (n=111, 245), VTD (n=90, 19%) and Bortezomib-Dexamethasone (Vd) (n=84, 18%). 69% TE and 59% TI patients had partial response or better after first line. 41% of TE patients actually received an Autologous Stem Cell Transplantation (ASCT) after 1 line. 19% of TI patients received an ASCT. Of note, in 78% of patients considered to have indication not taken to transplant, administrative barriers of access are reported. Mean follow-up for the entire group was 28.35 months (SD 29.27, CI 26.41-30.29). The median DFS was 62 months being significantly longer in TE patients (74 vs 53 months for TI, p=0.0002), estimated 5 years DFS 52% (TE 56% vs 46% for TI). Median OS was 88 months (Not reached for TE vs 75 moths for TI, p=0.0001), estimated 5 years OS 62% (TE 70% vs 56% for TI). Univariate analysis showed ISS at diagnosis, age and ASCT were significantly related to OS. On multivariate analysis ISS 3 (HR 1.89; p=0.004; CI 1.22-2.93) at diagnosis and ASCT (HR 0.26, p=0.0001, CI (0.18-0.39) were the only factors significantly associated with OS. 5 yrs. OS for patients that received ASCT was 80% in comparison to 48% if not done. Conclusion: At this timepoint data from RENEHOC is still limited, however, the potential of this growing registry is evident; until now little information about hematologic neoplasms in Colombia was available, this effort allows us to know the reality of our patients and plan relevant trials in our settings. We report here characteristic of a large cohort of MM patients in Colombia. OS and DFS are comparable with what have been published for similar patients in other latitudes. Consolidation with ASCT was the most important factor affecting prognosis in this cohort; the low transplant rate has to be addressed to improve outcomes for myeloma patients in Colombia. Figure Disclosures Abello: Abbvie: Consultancy, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Honoraria. Sossa:Takeda: Honoraria; Novo: Honoraria; Astellas: Honoraria; Roche: Honoraria. Idrobo:Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Henao-Uribe:Alexion: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

Prognostic Factors Of Response and Survival To Azacitidine (AZA) +/- EPO In RBC Transfusion Dependent (TD) IPSS Low and Int-1 (LR) MDS Resistant To EPO, With Particular Emphasis Of Genetic Lesions: A Study By The GFM

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 658-658 ◽  
Author(s):  
Sylvain Thepot ◽  
Raouf Ben Abdelali ◽  
Sylvie Chevret ◽  
Aline Renneville ◽  
Odile Beyne Rauzy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Genetic Markers ◽  
Research Funding ◽  
Prognostic Value ◽  
Response Rate ◽  
Univariate Analysis ◽  
Snp Array ◽  
Erythroid Response ◽  
Rbc Transfusion

Abstract Background Although anemia of LR MDS initially responds to erythroid stimulating agents (ESA) in 40-50% of patients, response is generally transient. AZA may lead to RBC transfusion independence (RBC-TI) in 30-40% of LR-MDS patients but it has not been studied prospectively in those resistant to ESA. While prognostic factors of response and survival to AZA have been largely analysed in high risk MDS, including by our group (Itzykson, Blood, 2011), they remain uncertain in LR-MDS, especially regarding new genetic factors. We previously reported (J Clin Oncol 30, 2012 # 6523) in a randomized phase II trial comparing AZA and AZA+EPO in 93 LR-MDS that were RBC-TD and resistant to ESA, a similar erythroid response rate in the 2 treatment arms (NCT01015352). Here, we report prognostic factors of response and overall survival in this trial, including genetic markers (SNP array-based karyotype and somatic mutations). Methods Patients included in the trial received AZA 75mg/m2/d for 5 days every 28 days for 6 cycles (AZA arm) or with added EPO 60000U/week (AZA+EPO arm). Erythroid response was evaluated after 4 and 6 cycles of AZA, according to the IWG 2000 criteria. Responders were then eligible for 12 AZA+/-EPO maintenance cycles. Affymetrix SNP array 6.0 (SNPa) analysis was performed at baseline on marrow mononuclear cells, and mutations of SF3B1, TET2, DNMT3A, ASXL1, JAK2 and 19 other genes were screened by next generation sequencing and validated by Sanger sequencing. The following factors were analysed for their prognostic value on erythroid response (IWG 2000) and survival: age, gender, IPSS, IPSS cytogenetics, WHO diagnosis, time since MDS diagnosis, SNPa karyotype, SF3B1, TET2, DNMT3A, ASXL1 and JAK2 mutations. Results In the 93 patients, M/F was 65/28; median age 72 y (IQR: 65-78); WHO diagnosis: RA 5.3%, RARS 40.9%, RCMD 15.1%, RCMD-RS 17.2%, RAEB-1 12.9%, CMML 7.5%, MDS-U 1%. Median MDS duration prior to inclusion was 37.2 months. IPSS was low in 35 and int-1 in 57 patients (NA in 1). IPSS cytogenetics was fav in 65, int in 9, defav in 2 patients, and failed or not done at study entry in 17 (but cytogenetics at MDS diagnosis was available in 16 of them). An abnormal SNPa karyotype was present in 33/79 patients analysed, including 9 with normal conventional cytogenetics. SF3B1, TET2, DNMT3A, ASXL1 and JAK2 mutations were detected in 59/86, 29/87, 12/87, 5/89 and 3/87 patients. Of the 19 other genes analysed, 12 showed no mutation and 7 (UA2F1, CBL, EZH2, RUNX1, ETV6, KIT, IDH2) were mutated in ≤3 patients and were not further considered in this analysis. In ITT analysis (N=93), erythroid response was 34% after 4 courses (37.5 % vs. 31% in the AZA and AZA+EPO arms, respectively, p=0.82) and 30% after 6 courses (35% vs. 24%, p=1.00). In univariate analysis, none of the factors listed above, including genetic markers, significantly predicted treatment response after 4 or 6 courses, while a trend was observed for a higher response rate after 6 cycles for SF3B1 mutated versus wt. patients (35.6 vs. 14.8 % respectively, P=0.07). Median follow-up of the 93 patients was 30 months (IQR: 23-34). Five patients developed AML (1 in AZA arm and 4 in AZA+EPO arm, P=0.19), all 5 in non-responders after 6 cycles. Median OS was 42.2 months and 2.5 years-OS 79.2% (95%CI: 71.2-88.1), with no difference between randomization arms (P=0.69). In univariate analysis, a shorter time since MDS diagnosis (HR=0.97, 95%CI: 0.95-0.99,P=0.011), IPSS int-1 (HR=2.83, 95%CI: 1.05-7.63, P=0.04), an abnormal SNPa karyotype (HR=3.01, 95%CI: 1.26-7.22, P=0.013) and presence of ASXL1 mutation (HR=5.08, 95%CI: 1.48-17.48, P=0.010) were associated with worse survival. In multivariate analysis, however, only time since MDS diagnosis (HR=0.97, 95%CI: 0.95-0.99) and abnormal SNPa karyotype (HR=2.92, 95%CI: 1.07-8.01) remained of prognostic value. Conclusions In this prospective AZA trial in LR-MDS resistant to ESA, no significant prognostic factor for response to AZA+/- EPO was identified, but a trend for better response (p=0.07) was seen in SF3B1 mutated patients, i.e 2/3 of patients. Among mutations analysed, only ASXL1 mutation predicted survival in univariate analysis, while abnormal SNPa karyotype predicted survival both in univariate and multivariate analysis (together with MDS duration). Thus, SNP array-based karyotyping and ASXL1 gene mutation analysis may become important tools to predict the long-term outcome of ESA resistant LR-MDS treated by AZA Disclosures: Guerci-Bresler: Novartis: Honoraria; BMS: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Fenaux:Celgene, Inc: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gardin:Celgene, inc: Research Funding.

Outcomes for Myeloma in the Era of Lenalidomide Maintenance Are Not Different Among Ethnic Groups Following Autologous Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3973-3973
Author(s):  
Chandra Pooja ◽  
Ajay K. Nooka ◽  
Monica S. Chatwal ◽  
Sungjin Kim ◽  
Zhengjia Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Maintenance Therapy ◽  
Ethnic Groups ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Post Transplant ◽  
Factors Associated ◽  
Lytic Lesions ◽  
White Patients

Abstract Background: Multiple myeloma (MM) is the most common hematological malignancy among African Americans (AA). The introduction of postransplant maintenance has had a significant improvement in progression free and overall survival for myeloma patients as demonstrated in large phase III clinical trials. However, the impact of race on the outcome of patients receiving maintenance treatment remains unknown. Methodology: We conducted a retrospective analysis of 299 consecutive patients transplanted for MM from 2005 to 2013 at the Winship Cancer Institute of Emory University. Survival analyses were estimated by Kaplan-Meier methods and univariate and multivariate analysis were performed using a cox proportional hazard model. Results: Baseline characteristics such as stage (International Staging System, ISS), presence of lytic lesions or plasmocytomas, immunoglobulin subtype, and cytogenetic risk category at presentation, were comparable between AA and white patients. Among AA, 57.1% received triple therapy with an immune modulator and a proteasome inhibitor (IMID+PI, lenalidomide (R) or thalidomide (T) and bortezomib (V) and dexamethasone), 49% received doublets (RD, TD or VD) and 29% received other bortezomib based regimens. In white patients 50.3% were treated with IMID+PI, 37% with doublets, 13.6% with received other bortezomib based regimens. Both populations had comparable ORR and >VGPR at day 100 (AA: ORR:90.74% and >VGPR:74.07% vs White ORR:90.65% and >VGPR: 77.57%, p>0.1). Of the 299 patients, 128 patients underwent maintenance treatment with lenalidomide (AA: 61 and White:67 patients) while 171 did not receive lenalidmode as they transplanted prior approval of lenalidomide maintenance. Maintenance treatments improved progression free survival in both ethnic cohorts. AA patients receiving maintenance therapy have not yet reached their median PFS with a median follow up of 8 years (60%), while median PFS was 4.8 years among those who did not receive maintenance (p=0.4). Similarly, in white patients, the PFS improved from 2.8 years without maintenance to 5.4 years with maintenance (p=0.01). Furthermore race did not affect PFS in both maintenance treated cohorts. Within the cohort of patients that did not receive maintenance therapy, we observed a trend of improvement in overall survival in AA patients ( p=0.06), which could suggest difference in the risk of the disease. However, no differences in staging or cytogenetics were identified between both ethnic groups at diagnosis that could explain this difference. Factors associated with longer PFS in univariate and multivariate analysis included AA race and immunoglobulin subtype (IgG and kappa light chain MM). In AA multivariate analysis identified the presence of lytic lesions as a factors associated with shorter PFS. In white patients, factors such as plasma cell leukemia at diagnosis were associated with worst PFS. In conclusion, race did not impact the improvement in PFS associated with post-transplant maintenance therapy. To our knowledge this preliminary analysis provides the first assessment of the influence of race in MM outcomes post-transplant during the lenalidomide maintenance era Disclosures Lonial: Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

scholarly journals Predicting Early Mortality in Multiple Myeloma Patients Treated with Novel Agents

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5641-5641
Author(s):  
Catarina Geraldes ◽  
Adriana Roque ◽  
Ana Bela Sarmento-Ribeiro ◽  
Maria Leticia Ribeiro ◽  
Rui Bergantim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Response Rate ◽  
Early Mortality ◽  
Novel Agents ◽  
Short Term ◽  
Term Outcome ◽  
Risk Of Death ◽  
Short Term Outcome ◽  
Increased Risk

Abstract BACKGROUND: Despite remarkable therapeutic advances in the last 2 decades and a major improvement in survival, a number of multiple myeloma (MM) patients (pts) present a short-term outcome. AIMS: Our aim was to identify the main factors (baseline characteristics, response to therapy, relapse features) determining early mortality (EM) among a cohort of newly diagnosed symptomatic MM pts treated with novel agents. METHODS: We conducted a national multicenter retrospective study, including a cohort of symptomatic MM pts diagnosed between January/2010 and June/2017, treated with novel agents (bortezomib, thalidomide or lenalidomide) with the maximum age of 75 years-old and living <3 years (y) after diagnosis. We considered EM as pts living <12 months (m). All pts were dead at the time of the analysis. Data were collected from medical registries and databases. Response to treatment was evaluated according to the International Myeloma Working Group (IMWG) consensus criteria (2016). Statistical analysis was performed using STATA v.14.2 and significant levels were set at p<0.05. All risk factors with p<0.15 in the univariate model were further entered into the multivariate analysis. RESULTS: A total of 142 pts were included in the study, 58% male and the median age at diagnosis was 65 y (27-75). IgG was the most frequent subtype (41%), followed by IgA (32%) and light-chain κ (14%) and λ (9%). At diagnosis, renal impairment (RI) was present in 32%, extramedullary disease (EMD) in 18% and bone disease in 69% of the pts; 58.3% were in stage III and 30.6% in stage II (ISS). Fluorescent in situ hybridization analysis was performed in 76 pts, 45% presenting high-risk cytogenetic abnormalities (HRC) [del(17p) and/or t(4;14) and/or t(14;16)]. Hypertension was present at diagnosis in 32% and diabetes in 18% pts. First-line therapy (1stL) included novel agents in 97% of the pts (64% bortezomib-based (Bor), 23% thalidomide-based (Thal) and 10% bortezomib plus IMID-based (BorIM). Response evaluation showed an overall response rate (ORR) of 73% (12% CR; 25% VGPR; 36% PR); 27% were refractory. Median time to response was 3.2m. Median number of therapy lines was 2 (1-3); 65% of the pts were refractory or progressed after 1stL therapy, 18% developed extramedullary disease (EMD) and 5 pts progressed to plasma cell leukemia. In pts receiving a 2ndL therapy, treatment-free interval was 9.2m and the most used regimens were lenalidomide (33%), Thal (25%), Bor (14%) and BorIM (11%) -based. ORR to 2ndL was 19.5% (3.4% VGPR and 16.1% PR). Six-month, 1-year and 2-years mortality was 7%, 27% and 65%, respectively. Median time until death was 18.2m; 55% of the pts died directly from disease progression (DP) and 45% from other causes [infection in 68% (only 17% of whom in DP), and cardiovascular complications in 13%]. In our study, prior hypertension (HR 1.53; 95% CI 1.01-2.32; p=0.046) and relapse with EMD (HR 2.0; 95% CI 1.23-3.26; p=0.005) were associated with increased risk of death. Pts≥70y also showed an increased risk of death, although not statistically significant (HR 1.42; 95% CI 0.96-2.12; p=0.081). In our cohort, refractoriness to 1stL treatment was not related to a significant increased risk of death (HR 1.48; 95% CI 0.91-2.40; p=0.11). Moreover, age, HRC, ISS stage, RI, bone disease and lactate dehydrogenase levels didn´t show a mortality predictive value. When comparing pts living <1y (EM) with pts living 1-3y, we identified the lack of at least PR (42.1% vs 21.2%, respectively; p=0.013) and a shorter time to 2ndL treatment (1.2 vs 10.0m; p=0.033) as predictors of death within the first 12m. Finally, in a multivariate analysis only the age at diagnosis >70y (HR 2.11; 95% CI 1.22-3.65; p=0.008) and EMD at relapse/progression (HR 2.55; 95% CI 1.45-4.50; p=0.001) predicted higher risk of mortality. CONCLUSIONS: ORR to 1stL therapy was similar to the generally expected response rate, showing that IMWG response criteria are not adequate to predict short-term outcome in the era of novel agents. The same was observed with classical baseline risk stratification features, raising the importance of defining a more accurate strategy to predict survival in MM pts. Refractory disease after 2ndL (higher than generally reported) and infections were the leading contributors to early death in our pts cohort. These data may provide new opportunities to define patient-adapted treatment strategies in order to decrease EM and improve overall survival in MM. Disclosures No relevant conflicts of interest to declare.

Very Good Partial Response and Complete Response Predict Superior Overall Survival and Progression Free Survival After Single Autologous Stem Cell Transplant in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

scholarly journals Is There a Preferred Infusional Regimen for Patients with Relapsed/Refractory Multiple Myeloma?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4757-4757
Author(s):  
Patrick T. Griffin ◽  
Viet Q. Ho ◽  
William Fulp ◽  
Taiga Nishihori ◽  
Kenneth H. Shain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Adverse Events ◽  
Treatment Outcomes ◽  
Retrospective Analysis ◽  
Novel Agents ◽  
Published Data ◽  
Bridge To Transplant ◽  
Eligible Population ◽  
The Impact

Abstract Introduction: Despite the impact of novel agents, many patients with multiple myeloma (MM) still require intensive infusional chemotherapy regimens, such as dexamethasone, cyclophosphamide, etoposide, cisplatin (DCEP), bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide (VDT-PACE), or cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD), especially in the setting of proliferative relapsed/refractory disease. To our knowledge, there are no published data comparing the different infusional regimens. Here, we present a retrospective analysis comparing the efficacy and safety of the three most commonly used MM salvage regimens in the era of novel agents. Methods: Patients with a diagnosis of relapsed/refractory MM who received one of the three chemotherapy regimens (DCEP, VDT-PACE, or CVAD) between 01/2005 and 12/2013 were identified through the Moffitt Total Cancer Care Database. Clinical variables were abstracted from the patient records. The IMWG criteria were used to assess response. Transplant eligibility was determined based on the assessment of the treating physician. Progression-free survival (PFS) and overall survival (OS) for each group were estimated from the initiation of salvage therapy using the Kaplan-Meier method. Multivariate predictors of survival were assessed using the Cox proportional hazards model by backward elimination. Results: A total of 107 patients receiving one of the 3 regimens for relapsed/refractory MM were identified (DCEP 52, VDT-PACE 22, CVAD 33). Relevant patient characteristics, treatment outcomes, and adverse events are described in Table 1. Prior therapy history was similar between the 3 groups in regard to lenalidomide (77.6%), bortezomib (88.8%), and autologous transplant (53.3%). An analysis of treatment outcomes revealed no statistically significant differences in response, PFS, or OS between the 3 regimens. There appeared to be a trend towards more FN in the VDT-PACE group, as well as prolonged hospitalization in the CVAD group. On multivariate analysis of the entire cohort, transplant eligibility prior to salvage treatment was the only significant predictor of OS (HR 0.22, p<0.001), whereas the treatment regimen was not significant (p=0.411). In fact, for the non-transplant eligible population, the median OS was only 3.09 months (95% CI, 2.17-4.02), versus 16.70 months (95% CI 11.45-21.97) for those patients deemed transplant eligible. On multivariate analysis of the transplant eligible population, performance status (HR 2.10, p=0.012) and extramedullary disease (HR 3.71, p=0.002) were significantly correlated with OS. Conclusions: In this retrospective analysis, there were no statistically significant differences in outcomes between the three MM salvage regimens. Of note, the more intensive regimen, VDT-PACE, did not demonstrate superior disease response or survival. For patients in whom a bridge to transplant was not planned, infusional chemotherapy was associated with poor outcomes, and should not be considered in that setting given the significant toxicities. There was a trend towards fewer adverse events in the DCEP treated patients. Abstract 4757. Table 1.Characteristics, N (%) DCEP n=52 VDT-PACE n=22 CVAD n=33 p-value Age (yrs), median (range)57.6 (43-73)54.5 (29-68)56.9 (41-73)0.054Creatinine (mg/dL), median (range)0.90 (0.6-2.8)1.25 (0.6-6.6)2.20 (0.6-12.9)<0.001Extramedullary Disease, N (%)15 (28.8)7 (31.8)3 (9.1)0.056Circulating Plasma Cells >5%, N (%)4 (7.7)4 (18.2)7 (21.2)0.169High Risk Cytogenetics, N (%)18 (34.6)6 (27.3)8 (24.2)0.803+1q219 (17.3)1 (4.5)2 (6.1)t(4;14)5 (9.6)02 (6.1)-17p11 (21.2)6 (27.3)4 (12.1)Prior Regimens, N (%)3 (1-9)3 (1-13)3 (1-7)0.514Transplant Eligible, N (%)32 (61.5)14 (63.7)17 (51.5)0.578OutcomesVGPR or better, N (%)9 (17.3)7 (31.8)4 (12.1)0.284PR or better, N (%)27 (51.9)16 (72.7)16 (48.5)0.386Successful Bridge to Transplant, N (%)20/32 (62.5)8/14 (57.1)11/17 (64.7)0.907Median PFS, mo. (95% CI)3.78 (1.96-5.60)4.54 (1.67-7.41)5.79 (2.10-9.48)0.801Median OS, mo. (95% CI)8.26 (5.52-10.99)8.52 (3.16-13.87)8.22 (0.00-18.46)0.835Adverse Events, N (%)Prolonged Hospitalization4 (7.7)1 (4.5)7 (21.2)0.084Re-Hospitalization for Adverse Event15 (29.4)8 (36.4)13 (40.6)0.563Febrile Neutropenia15 (29.4)11 (50.0)13 (39.4)0.230Treatment Related Mortality3 (5.8)1 (4.5)3 (9.1)0.762 Disclosures No relevant conflicts of interest to declare.

scholarly journals Early Mortality in Patients with Multiple Myeloma Treated with Novel Agents - Analysis from Polish Myeloma Study Group

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Grzegorz Charlinski ◽  
Agata Tyczyńska ◽  
Jan M Zaucha ◽  
Adriana Czyz ◽  
Jarosław Czyż ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Early Mortality ◽  
Novel Agents ◽  
Factors Associated ◽  
For Profit ◽  
Health Care Company ◽  
Care Company

Background Although the introduction of novel agents improved the survival outcomes in patients with multiple myeloma (MM), some patients died within one year (early mortality, EM) following diagnosis. In this study, we evaluated the EM rate, and investigated the risk factors associated with EM in MM patients. Aims In this study we investigated risk factors associated with EM in MM patients initially treated with novel-agent containing regimen. Methods We conducted a multicenter (15 Polish sites) retrospective study a cohort of symptomatic MM pts diagnosed between October 2006 and November 2019 and living &lt; 365 days (d) after diagnosis. All pts were dead at the time of the analysis. Data were collected from medical registries and databases. Mortality rate and cause at 2, 6, and 12 months following diagnosis was evaluated. Clinical staging was performed using the International Staging System (ISS). Response to treatment was evaluated according to the International Myeloma Working Group (IMWG) consensus criteria (2016). Statistical analysis was performed using R-studio v.1.3.959. and significant levels were set at p&lt;0.05. Results Of the 197 pts were included in the study, 112 (57%) male and the median age at diagnosis was 69 y (41-91). The MM type of 100 patients (52%) was Immunoglobulin (Ig) G, 24% of patients was IgA, 15% of patients had light chain disease, and 3% of patients IgM or IgD. At diagnosis, renal impairment (RI) was present in 43%, extramedullary disease (EMD) in 15% of the pts; 15% were in stage I, 10% in stage II, 60% in stage III (ISS) and 15% not done. Fluorescent in situ hybridization analysis was performed in 59 pts, 69% presenting high-risk cytogenetic abnormalities (HRC) [t(4;14), t(14;16), t(14;20) or del17p]. 54% pts were &gt;2 comorbidities at diagnosis. Heart disease was presented at diagnosis in 57% pts and diabetes in 22% pts. First-line treatment (1stL), 41% of the pts patients were bortezomib-based (Bor) regimens, 25% Bor with thalidomide (VT)-based, 22% IMiD-based and 13% others. Response evaluation showed an overall response rate (ORR) of 44% (3% CR; 14% VGPR; 27% PR). 46% pts survived &lt; 2 months, 29%; 2-6 months and 25%: 6-12 month. Median time until death was 2.5 month; 31% of pts died directly from progression disease (PD), and 69% from other causes [infection in 66%, cardiovascular complications in 27%, RI in 8%]. In our study, age &gt; 65 y (HR 1.67; 95% CI 1.24-2.26; p=0.0007), and &gt;75 y (HR 1.5; 95% CI 1.10-2.03; p=0.0087), &gt;2 comorbidities (p=0.002), heart disease (HR 2.12; 95% CI 1.57-2.85; p &lt; 0.0001), RI (HR 0.7; 95% CI 0.53-0.95; p=0.029), dependence of dialysis (HR 1.50; 95% CI 1.05-2.14; p=0.029) were associated with increased risk of death. Mortality predictive value showed HRC (p=0.05), lactate dehydrogenase levels (HR 0.65; 95% CI 0.38-1.1; p=0.002), and &gt;PR (HR 0.30; 95% CI 0.21-0.43; p&lt;0.0001). Moreover, sex, hypertension, diabetes, type of MM, extramedullary disease, ISS stage, hemoglobin level, count of platelets didn't show a mortality predictive value. Conclusions IMWG response criteria are not adequate to predict short-term outcome in the era of novel agents. Infections and refractory disease were the leading contributors to early death in our pts cohort. These data may provide new opportunities to define patient-adapted treatment strategies in order to decrease EM and improve overall survival in MM. Disclosures Wrobel: BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Roche: Research Funding; Janssen: Honoraria. Robak:Abbvie, Pharmacyclics, Gilead, GlaxoSmithKline, Novartis, Janssen, F. Hoffmann-La Roche, Acerta, AstraZeneca, BioGene, UCB: Research Funding; F. Hoffmann-La Roche, Abbvie, Pharmacyclics, Novartis, Janssen, Acerta, AstraZeneca, BioGene, UCB, Sandoz: Honoraria. Robak:Bristol Meyers Squibb: Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Honoraria, Research Funding; Takeda: Consultancy; GSK: Research Funding; UTX-TGR: Research Funding; Acerta: Research Funding; BioGene: Honoraria, Research Funding; Morphosys: Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Octapharma: Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Medical University of Lodz: Current Employment; UCB: Honoraria, Research Funding; Pfizer: Research Funding; Momenta: Consultancy; Sandoz: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding.

Induction with New Drugs and Planned Autologous Followed by Non-Myeloablative Allogeneic Transplantation in Newly Diagnosed Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4330-4330
Author(s):  
Luisa Giaccone ◽  
Moreno Festuccia ◽  
Roberto Sorasio ◽  
Nicola Mordini ◽  
Fabrizio Carnevale Schianca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
New Drugs ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Post Transplant ◽  
The Impact

Abstract Abstract 4330 Introduction Immunomodulatory drugs have recently changed the treatment options in multiple myeloma. Moreover, thalidomide, bortezomib and lenalidomide have also been used in the setting of allografting as post-transplant salvage therapy or as maintenance. We are currently evaluating the impact of new drugs as induction therapy in newly diagnosed multiple myeloma before a planned standard autograft followed by a non-myeloablative allograft (Tandem auto-allo). Patients and methods Twenty-five newly diagnosed patients (median age 55 years old, range 26-65) entered a recently designed prospective phase II program of tandem auto-allo which included the use of so-called new drugs during induction. Here, we report data on the first 11 evaluable patients with a follow up of at least 1 month after the allograft. Induction consisted of lenalidomide and dexamethasone (n=5), thalidomide and dexamethasone (n=4), or bortemomib-containing regimens (n=2), followed by G-CSF mobilized peripheral blood stem cell harvest. A standard autograft after melphalan 200 mg/m2 was planned 2-4 months before a low-dose (2 Gy) TBI-based allograft from an HLA-identical sibling. GVHD prophylaxis consisted of cyclosporin and mycophenolate mofetil. Disease status at allografting and post-transplant outcomes were compared to those of 22 patients pair-matched for beta2microglobulin and age, who underwent tandem auto-allo after induction with VAD-based regimens without new drugs (Blood, 2009). Results At the time of allografting after induction with new drugs and the autograft overall response rate was 81% (9/11), including a immunofixation-negative complete remission (CR). Following allografting, all patients promptly achieved donor engraftment. After a median follow-up of 11 months (2-26), all patients are alive and the overall response rate was 91% (10/11). Incidence of grade II-IV GVHD was 34% (4/11), including 1 patient with grade III GVHD. Chronic GVHD was observed in 40% (4/10) of patients with at least 3 months of follow-up. The induction with new drugs did not increase allotransplant-related toxicity or incidence of acute GVHD (Table 1). We observed a higher response disease before allografting in patients treated with new drugs. Conclusions Induction with lenalidomide, thalidomide or bortezomib does not impact feasibility and safety of tandem auto-allo. Longer follow up and a larger cohort of patients are necessary to evaluate the impact of new drugs in improving disease control post-tandem auto-allo. Disclosures: Patriarca: Janssen Cilag: Honoraria; Celgene: Honoraria. Boccadoro:Celgene: Consultancy, advisory committees, Research Funding; Pharmion: Consultancy, advisory committees, Research Funding; Janssen Cilag: Consultancy, advisory committees, Research Funding.

The Achievement of a 3-Month Complete Cytogenetic Response (3-mo CCyR) to Second Generation (2nd) Tyrosine Kinase Inhibitors (TKI) Post Imatinib Failure Is the Only Predictive Factor for Event-Free (EFS) and Overall Survival (OS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2289-2289
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Jenny Shan ◽  
Susan O'Brien ◽  
Alfonso Quintas-Cardama ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Predictive Factor ◽  
Research Funding ◽  
Second Generation ◽  
Univariate Analysis ◽  
Response Rates ◽  
Cytogenetic Response ◽  
Older Age ◽  
Imatinib Therapy ◽  
Factors Associated

Abstract Abstract 2289 2nd TKIs such as dasatinib and nilotinib have shown significant activity post imatinib failure, with high rates of hematologic and cytogenetic responses. Achieving early cytogenetic response is a known major determinant of outcome in patients (pts) treated with imatinib. In a previous report from our institution, we reported that the achievement of a previous cytogenetic response to imatinib therapy is a major predictive factor in pts receiving a 2nd TKI. The aim of our study was to assess the impact of a 3-mo CCyR on EFS and OS of pts treated with 2nd TKI post imatinib failure. 123 pts with chronic phase (CP) CML after imatinib failure were treated with dasatinib (n=78) or nilotinib (n=45). Median age was 56 years (range, 21–83). Median duration of CP (CML diagnosis to start of second generation TKI) was 67 months (range, 2–268). Their best response to imatinib was complete hematologic response (CHR) only in 24%, and cytogenetic response in 63% (28% complete, 17% partial, 18% minor). The CHR rates were 87% and 84% in pts treated with dasatinib and nilotinib, respectively (p=0.75). The major cytogenetic response rates were 64% and 62% (p=0.85), and the complete cytogenetic response rates were 60% and 56% (p=0.70). The rates of cytogenetic response at 3-, 6- and 12-mo were 59%, 63% and 69% (p=0.39) and 60%, 55% and 51% (p= 0.7) in pts treated with dasatinib and nilotinib, respectively, and the rates of CCyR at these same time-points were 32%, 41% and 48% (p= 0.13) and 36%, 36% and 35% (p= 0.99), respectively. The 3-year EFS and OS rates were 53% and 84%, respectively. Factors associated with poor EFS in the univariate were older age (> 55 years), lack of any cytogenetic response to previous imatinib therapy, more than ≥90% Philadelphia-positive metaphases (Ph) at the start of 2nd TKI therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, the lack of a 3-mo CCyR to 2nd TKI therapy (HR= 4.5; p<0.001) was selected as the only independent factor associated with poor EFS, with a 3-year EFS rates of 74% and 43% for pts with and without 3-mo CCyR, respectively. Factors associated with poor OS in the univariate analysis were older age (>55 years), increasing marrow blasts, lack of any cytogenetic response to previous imatinib therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, only a lack of a 3-mo CCyR to 2nd TKI therapy (HR=5.4; p = 0.03) was independently associated with a lower probability of survival; the 3-year OS rates were 98% and 79% for pts with and without 3-mo CCyR, respectively. Therefore we analyzed factors that were associated with the 3-mo achievement of a CCyR. In the univariate analysis, high hemoglobin level, previous cytogenetic response to imatinib therapy, and ≤90% Ph, and increasing marrow blast% were associated with the achievement of a CCyR at 3 months of therapy with 2nd TKI. In the subsequent multivariate analysis for response, Ph% >90 and Hgb <12.0 were independent poor predictive factor for 3-mo CCyR. In conclusion, the achievement of a 3-mo CCyR is the only predictor of outcome in pts treated with 2nd TKI post imatinib failure. Pts with high tumor burden (defined Ph >90%) and anemia (Hgb< 12.0) have a low likelihood of achieving a 3-mo CCyR to 2nd TKI therapy and therefore should be offered additional options. Disclosures: Jabbour: BMS: Honoraria; Novartis: Honoraria. Cortes: Novartis: Research Funding; BMS: Consultancy; Pfizer: Consultancy, Research Funding.

The Impact of Induction Regimen Choice on Transplant Outcome and Survival in Newly Diagnosed Multiple Myeloma in the Era of Novel Agents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3044-3044
Author(s):  
Rajshekhar Chakraborty ◽  
Shaji Kumar ◽  
Francis Buadi ◽  
David Dingli ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Novel Agents ◽  
Agent Based ◽  
Induction Regimen ◽  
Baseline Characteristics ◽  
The Impact ◽  
Novel Agent

Abstract Background Induction with novel agents, including proteasome inhibitors and immunomodulators, prior to autologous stem cell transplantation (ASCT) is the standard of care frontline treatment of transplant-eligible patients with multiple myeloma (MM). Common novel agent-based induction regimens include three drug combinations with a backbone of bortezomib (V), thalidomide (T) and/or lenalidomide (R). There is limited information on the comparative efficacy of novel regimens used as part of initial therapy prior to an ASCT in terms of overall survival (OS). To address this question, we retrospectively analyzed 1096 consecutive patients undergoing ASCT for MM at Mayo Clinic. Methods Study patients included those who underwent first transplant within 12 months of diagnosis, did not receive more than one induction regimen, did not relapse prior to transplant and did not receive treatment for smoldering MM in the past. Baseline characteristics, response rates and survival data were extracted from an electronic medical record and statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Choice of induction regimen was almost exclusively made by the referring physician. Results Median age at diagnosis was 60.3 years (Interquartile range 53.9-65.9). ISS staging at diagnosis was available for 49.7% of patients, of which, 34.2%, 39.3% and 26.5% of patients had ISS stage 1, 2 and 3 disease, respectively. Estimated median follow up was 65.6 months (95% CI 58.3-73.3). Baseline characteristics of patients by initial treatment have been summarized in table 1. Major subgroups by induction therapy included patients receiving Cy-Bor-d (n=193, 17.6%), Vd (n=64, 5.83%), Rd (n=253, 23.1%), VRd (n=126, 34.6%), Td (n=157, 14.3%) and VAD or dexamethasone alone as the non-novel agent comparator group (n=229, 20.9%). Median overall survival (OS) was significantly different between novel agent-based and conventional regimens (Log-rank test; p=0.0029), which were 102.7 months (95% CI, 95.2-112.2) and 78.8 months (95% CI, 67.8-92.6) respectively. Median OS with each regimen is shown in table 1. Among novel agent-based regimens, there was no significant difference in median OS, except Td, which was inferior to Rd (HR 1.62; 95% CI 1.17-2.24). Conclusion We cannot demonstrate with overall survival as an endpoint that the doublets of Vd and Rd are inferior to VRd or Cy-bor-d. There were insufficient patients treated with VTd to be included. Our study shows that the choice of novel induction regimen prior to ASCT does not affect survival (with the exception of Td being inferior to Rd), reflecting the wide array of effective salvage options. However, further prospective randomized clinical trials comparing these regimens are required to validate these findings. Table 1. Baseline characteristics and overall survival. Baseline characteristics and survival Cy-Bor-d (n=193) Vd (n=64) Rd (n=253) VRd (n=126) Td (n=157) VAD or Dex (n=229) p-value Median age 61.9 62.15 60.8 60.8 59.3 58.5 0.0041 Sex (percent males) 56.48 57.81 56.92 61.91 57.96 59.82 0.9271 ISS at diagnosis 1:24.82% 2:40.69% 3:34.48% 1:29.73% 2:24.32% 3:45.94% 1:40% 2:43.78% 3:16.22% 1:41.76% 2:34.06% 3:24.18% 1:28% 2:36% 3:36% 1:20% 2:60% 3:20% 0.0005 Median follow-up (95% CI) 20.3 (17.1-22.7) 49.5 (44.7-55.7) 59 (54.5-67) 26.9 (22.8-30.7) 126.7 (120.2-132.9) 143.4 (132.5-152.6) <0.0001 Median OS Not reached (Estimated 5 year OS rate 75%) 97.2 months (95% CI, 66.6-NR) 112 months (95% CI, 97.4-124.3) Not reached (Estimated 5-year OS rate 77%) 81.1 months (95% CI, 59.1-99.1) 78.8 months (95% CI, 67.8-92.6) 0.0019 Figure 1. Figure 1. Disclosures Kumar: Onyx: Consultancy, Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria.

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