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.

Continued Improvement in Survival in Multiple Myeloma and the Impact of Novel Agents

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3972-3972 ◽  
Author(s):  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Morie A Gertz ◽  
Martha Q Lacy ◽  
John A Lust ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Initial Therapy ◽  
Novel Agents ◽  
The Novel ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Past ◽  
The Impact

Abstract Abstract 3972 Background: The treatment paradigm for myeloma has undergone a dramatic shift in the past decade with the introduction of the novel agents and their application at every stage of the treatment. We and others had previously shown that survival of patients with myeloma had improved in the earlier half of the last decade and attributed this to a combination of novel therapies as well as increased use of stem cell transplant. It is not clear if this momentum in improving survival has been maintained. We examined the survival trends of patients with newly diagnosed myeloma seen within the past decade to examine this question. Patients and Methods: We studied 1056 patients with newly diagnosed myeloma, who were seen at Mayo Clinic between January 1, 2001 and December 31, 2010; who were seen within 30 days of their diagnosis. For examination of the time trends, we grouped the time interval into two five year periods, 2001–2005 and 2006–2010. Survival was estimated using Kaplan Meier method and survival curves were compared by log rank test. Impact of various prognostic factors was evaluated using Cox proportional hazards test. Results: The median age at diagnosis was 65 (range; 22–92), and 59% were male. The median estimated follow up for the entire cohort was 4.6 years (95% CI; 4.4, 4.9) and 57% of the patients were alive at last follow up. The median overall survival (OS) for the entire cohort was 5.4 years (95% CI; 5, 6.3). The overall survival for patients in the 2001–2005 group was 4.6 years compared with not reached for the 2006–2010 cohort (P< 0.001). The five-year estimated OS was 48% for the earlier group compared with 66% for the latter group. The estimated 1-year survival was 90% for the recent cohort compared with 83% for the earlier cohort, suggesting improvements in the early mortality. Interestingly, the improvement was predominantly seen in the older age group (>65 years; 49%). The 5-year survival of the older patients improved significantly from 31% (2001–2005) to 56% (2006–2010) (P<0.001). In contrast, among younger patients (≤65 years of age), the 5-year survival improved only marginally from 63% (2001–2005) to 73% (2006–2010) (P=NS). One or more novel agents (Lenalidomide, thalidomide or bortezomib) were used as part of initial therapy in 631 (62% of 1021 in whom treatment data was available). The OS among of this group was 7.3 years (95% CI; 5.9, NR) compared with 3.8 years (95% CI; 3.1, 4.6). In a multivariate model that included both use of novel agent and the year group, only the novel agent use was associated with improved survival suggesting that the improvement in the survival is related to the increased use of novel agents in the initial therapy. No significant differences were observed between the groups in terms of conventional prognostic factors. Conclusions: The current results confirm continued improvement in the overall survival of patients, even within the last 10 year period, and highlight the impact of initial therapy with novel agents. Most importantly, we demonstrate that the improved survival has primarily benefited older patients. Our study highlights that urgent need for additional new agents to provide further survival improvement for younger patients, and in order achieve a cure for this disease. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Cephalon: Research Funding; Genzyme: Research Funding. Dispenzieri:Celgene: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Janssen Research & Development: Research Funding. Gertz:Binding Site: Honoraria.

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

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.

Elevated Serum Lactate Dehydrogenase (LDH) Should Be Included Among the Variables Which Define High Risk Multiple myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2969-2969
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gkotzamanidou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Renal Impairment ◽  
Elevated Serum ◽  
Novel Agents ◽  
Serum Lactate Dehydrogenase ◽  
Agent Based ◽  
Poor Outcome ◽  
Novel Agent

Abstract Abstract 2969 LDH is elevated in approximately 10% of patients with newly-diagnosed, symptomatic, multiple myeloma (MM). In patients treated with conventional chemotherapy, elevated LDH is associated with poor outcome (Dimopoulos et al, Ann Intern Med 1991). In selected patients treated with combinations of novel agents and tandem transplantation, LDH is an independent prognostic factor and is associated with short event free and overall survival even when cytogenetic abnormalities and gene expression signature are considered (Barlogie et al, J Clin Oncol 2010). An analysis from our group has also suggested that LDH improves the prognostic value of the International Scoring System (ISS) for MM (Terpos et al, Eur J Hematol 2010). However, there is limited data about the prognostic importance of elevated LDH in unselected MM patients who have been treated upfront with novel agent-based regimens. To address this issue, we analyzed 180 consecutive, unselected patients from a single center in Athens, Greece, who were treated upfront with novel agent (thalidomide, bortezomib or lenalidomide)-based therapies. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Fifty-one per cent of our patients were older than 70 years of age. LDH was elevated (≥300 IU/L, upper limit of normal 225 IU/L) in 8% patients before initiation of treatment. Elevated LDH was associated with features of advanced disease such as ISS-3 stage (p=0.063) and impaired renal function (p=0.034). The objective response rate in patients with elevated LDH was 47% and in patients without elevated LDH was 79% (p=0.011). The median overall survival for all patients was 54 months. Elevated LDH was associated with poor outcome (median survival 21 months vs. 56 months for patients with LDH <300 IU/L, p=0.007). Other factors which were associated with inferior survival, in the univariate analysis were age >70 years (p<0.001), Hb <10 g/dl (p<0.001), platelet counts <130,000/ml (p<0.001), corrected serum calcium >11.5 g/dl (p=0.012), ISS-3 stage (p<0.001) and renal impairment (p=0.001). In the multivariate analysis, elevated serum LDH was an independent factor and had a major prognostic impact associated with a 5.4-fold increased risk for death (p<0.001). Furthermore, elevated serum LDH was more often associated with early death. We conclude that in unselected MM patients treated upfront with novel agents, serum LDH is a simple, inexpensive and readily available blood test, which identifies a subset of patients with poor outcome. Our data suggest that in future phase 3 trials, LDH should be taken into account for the stratification of patients. Furthermore, elevated baseline serum LDH should be included in the current criteria (i.e. poor risk cytogenetics, high plasma cell labeling index) which are being used to characterize high risk myeloma. Disclosures: No relevant conflicts of interest to declare.

Effect of Amp5q31 and Del12p13 on Survival of Patients with Multiple Myeloma Treated with Novel Agent-Based Regimens: A Single Center Experience on 172 Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1811-1811
Author(s):  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Despoina Iakovaki ◽  
Maria Gkotzamanidou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Survival ◽  
Chromosomal Aberrations ◽  
Median Overall Survival ◽  
Chromosomal Abnormalities ◽  
Newly Diagnosed ◽  
Single Center ◽  
Agent Based ◽  
Novel Agent

Abstract Abstract 1811 The presence of chromosomal aberrations is a characteristic feature of multiple myeloma (MM). Recently, Avet-Loiseau et al reported that amp5q31.3 and del12p13.31, detected by high-density, single-nucleotide polymorphism arrays analysis correlate with prognosis in MM patients who were treated upfront with conventional chemotherapy (JCO 2009; 27:4585–90). The aim of our study was to evaluate the effect of these chromosomal abberations on survival of patients with newly diagnosed MM or with relapsed/refractory myeloma who were treated with novel agent-based regimens. We studied 172 MM patients who were treated in a single center in Athens (Greece) during a 4-year period (2007–2011); 76 were newly-diagnosed and were treated upfront with either bortezomib- or IMiD-based regimens and 96 had relapsed or refractory MM and were treated with the combination of lenalidomide and dexamethasone with or without bortezomib (RD vs. VRD) based on the presence of previous peripheral neuropathy (Dimopoulos et al, Leukemia 2010;24:1769–78). A combined methodological approach of G-banding karyotypic analysis and interphase fluorescence in situ hybridization (FISH) was performed in all patients. G-banding analysis was performed according to the European Cytogenetic Guidelines and Quality Assurance (ECA, 2006). The clonality criteria and the karyotypic description followed the recommendations of the International System for Human Cytogenetic Nomenclature (ISCN, 2009). FISH was performed according to the Recommendations for FISH in MM (European Myeloma Network) on uncultured BM, either on cytoplasmic immunoglobulin-enhanced cells (cIg-FISH) or on nuclei from purified CD138+ plasma cells. Commercially available DNA probes (Abott-VYSIS) were used for the detection of del17p, del13q, add1q21, t(4;14) and t(14;16). The probes RP11-96J7 and RP11-578N7 (labeled by Empire Genomics, NY, USA) were used to detect amp5q31 and del12p13. The frequency of the studied chromosomal abnormalities is depicted in the table. There was a strong correlation between the presence of amp5q31 with hyperdiploidy (p=0.012) but amp5q31 did not correlate with the presence of any other of the studied chromosomal aberrations. The presence of del12p13 was correlated with the presence of del13q (p=0.001), t(4;14) (p=0.009) and del17p (p=0.005). Add1q21 also correlated with del13q (p<0.001), t(4;14) (p<0.001) and del17p (p=0.007). In patients with relapsed/refractory MM, who received either RD or VRD, the median overall survival was 19 months. Patients with amp5q31 had a median survival of 18 months (95% CI: 13–23 months) vs. 21 months of the others (95% CI: 8–35 months; p=0.737), while patients with del12p13 had a median survival of 27 months (95% CI: 0–57 months) vs. 19 months of the others (95% CI: 10–27 months; p=0.767). Of the other studied cytogenetic abnormalities, the presence of del17p (11 vs. 26 months; p=0.001), amp1q21 (12 vs. 26 months; p=0.001) and del13q by FISH (11 vs. 26 months; p=0.025), but not of t(4;14) (p=0.521), were associated with inferior overall survival. In patients with newly-diagnosed MM, the median overall survival was 57 months. The median survival of patients with amp5q31 was 46 months vs. 57 months of all others (p=0.315) and for patients with del12p13 has not been reached vs. 57 months of all others (p=0.379). In conclusion, amp5q31 and del12p13 are recurrent chromosomal abnormalities in MM. Amp5q31 is not associated with the presence of other genetic features, except hyperdiploidy. αmp5q31 or 12p13 was not predictive of survival ιn our series. However, further studies are needed in patients with newly diagnosed MM who receive novel agents upfront to validate the prognostic importance of amp5q31 and del12p13.TableCytogenetic abnormalityPatients at diagnosis (n=76)Relpased/refractory patients (n=96)p-valueamp5q3112 (15.7%)20 (20.8%)0.271amp5q31 as sole anomaly5 (6.5%)7 (7.2%)0.674del12p138 (10.5%)16 (16.6%)0.171del13q28 (36.8%)28 (29.1%)0.279del17p13 (17.1%)15 (15.6%)0.765add1q2115 (19.7%)26 (27%)0.303t(14;16)1 (1.3%)1 (1%)0.832t(4;14)4 (5.2%)10 (10.4%)0.221Hyperdiploidy/hypodiploidy10 (13.1%)/6 (7.8%)11 (11.4%)/13 (13.5%)0.301 Disclosures: No relevant conflicts of interest to declare.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma for Long-Term Follow-up: Single Center Results

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5836-5836
Author(s):  
Weiwei Sui ◽  
Dehui Zou ◽  
Gang An ◽  
Shuhui Deng ◽  
Yan Xu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
First Line ◽  
Hematopoietic Stem ◽  
Agent Based ◽  
Total Treatment ◽  
Long Term Follow Up ◽  
Baseline Characteristics

Abstract Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Patient Related Factors Have an Indepedent Impact on Overall Survival in Myelodysplastic Syndrome Patients: A Report of the MDS-Can Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 165-165
Author(s):  
Rena Buckstein ◽  
Richard A. Wells ◽  
Nancy Zhu ◽  
Thomas J. Nevill ◽  
Heather A Leitch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Physical Performance ◽  
Predictive Factors ◽  
Research Funding ◽  
Performance Tests ◽  
Related Factors ◽  
Risk Of Death ◽  
The Impact ◽  
Very High

Abstract Introduction: MDS is a disease of the elderly; yet, the impact of clinical frailty (an age-related vulnerability state created by a multidimensional loss of reserves) and patient-reported outcomes on overall survival (OS) are unknown. Rockwood et al. have developed a simple 9-point clinical frailty scale (CFS) that correlated highly with the risk of death, institutionalization, worsening health and hospital use (Rockwood K., CMAJ 2005). In a prospective, national MDS registry, participants have undergone annual evaluations with the following: (a) 3 geriatric physical performance tests, (b) Charlson (CCI) and Della Porta comorbidity index (DP-CCI) scores, (c) graded frailty using the Rockwood CFS, (d) disability assessments with the Lawton Brody SIADL, and (e) QOL using the EORTC QLQ C-30 and the EQ-5D. The results of these frailty assessments and the effects of these patient-related factors and reported outcomes on OS, in addition to the IPSS/revised IPSS, will be presented. Methods: Overall survival was measured from time to enrollment. Results from physical performance tests were divided into quintiles with higher scores indicating better performance. We used univariate and multivariable Cox proportional hazard model to determine significant predictive factors of overall survival (OS). The variables considered included age, IPSS, R-IPSS, ferritin, LDH, transfusion dependence, hemoglobin (hgb), ECOG, frailty, CCI and DP-CCI, grip strength, 4 M walk test, stand-sit test, modified short physical performance battery (SPPB), Lawton Brody SIADL, time from diagnosis and selected QOL domains including the EQ-5D summary score, EORTC physical functioning, dyspnea and fatigue scores. Results: 453 MDS patients (pts) have been consented and enrolled locally since January 2008 (n=231) and nationally since January 2012 (n=222). Median time from diagnosis was 5.8 mos (IQR 1.4-21). Median age was 73 y (range, 26-95 y), 65% were male and the R-IPSS scores were very low (14%), low (46%), intermediate (24%), high (10%) and very high (6%). Thirty-three % of pts were transfusion dependent at enrollment. Median CCI and DP-CCI scores were 1 (0-12) and 0 (0-6) respectively with 18% and 24% falling into the highest category scores. Median frailty scale score (n=346) was 3 (1-9) with 25% having scores indicating moderate (4-5) or severe (6-9) frailty. The CCI and DP-CCI strongly correlated (r=0.6; p< .0001) with each other, while frailty significantly but modestly correlated with them (r=0.3-0.35, p<.0001). With a median follow up (from enrollment) of 15 mos (95% CI: 13-16), 159 (35%) pts have died and 28 pts lost to follow up. Actuarial survival was 41.0 mos (range, 33.6 - 48.5 mos). When considering patient related factors - age, frailty, comorbidity (both indices), sex, ECOG, the 10 x stand sit test, the SPPB, Lawton Brody SIADL, and all QOL domains considered above were significantly predictive of OS. The multivariable model with the highest R2 included R-IPSS (p=.0004), frailty (1-3 vs 4-9, p= .004), CCI (0-1 vs >2, p=.03) and EORTC fatigue (p=.01) as summarized in Table 1 below. A frailty score > 3 predicted for worse survival (figure 1: 2 year OS 68.5% vs. 83.8%) and further refined survival within the R-IPSS categories (Figure 2). Frailty was also the single most predictive factor for OS from the start of azacitidine therapy (not shown). Conclusions: Patient-related factors such as frailty and comorbidity (that evaluate physiologic reserve and global fitness) should be considered in addition to traditional MDS prognostic indices. Abstract 165. Table. Independent Covariate Predictive factors at baseline Coefficient SE p -value HR 95% CI of HR R2 (%) Time from diagnosis (months) * 0.0335 0.1076 0.7557 1.034 0.837 1.277 17.29% R-IPSS (5 categories) <.0001 Very high vs. very low 2.5701 0.7289 0.0004 13.066 3.131 54.524 High vs. very low 2.1156 0.6437 0.0010 8.294 2.349 29.285 Intermediate vs. very low 1.0466 0.6430 0.1036 2.848 0.808 10.043 Low vs. very low 0.6346 0.6181 0.3045 1.886 0.562 6.334 Frailty (1-3 vs. 4-9) -0.8323 0.2905 0.0042 0.435 0.246 0.769 Comorbidity Charlson (0-1 vs. ³2) -0.5915 0.2749 0.0314 0.553 0.323 0.949 EORTC fatigue * 0.3671 0.1546 0.0176 1.443 1.066 1.954 natural log-transformation was applied for normalizing distribution Figure 1 Overall survival by Frailty (n=346) Figure 1. Overall survival by Frailty (n=346) Figure 2 Overall Survival by Frailty and R-IPSS Figure 2. Overall Survival by Frailty and R-IPSS Disclosures Buckstein: Celgene Canada: Research Funding. Wells:Celgene: Honoraria, Other, Research Funding; Novartis: Honoraria, Research Funding; Alexion: Honoraria, Research Funding. Leitch:Alexion: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Educational Grant Other, Honoraria, Research Funding. Shamy:Celgene: Honoraria, Other.

scholarly journals Narcotic Use in Multiple Myeloma Patients at the Time of ASCT and One-Year Follow up

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4726-4726
Author(s):  
Matthew Danish ◽  
Tabitha Copeland ◽  
Joseph Ho ◽  
Mansi Shah ◽  
Dennis Cooper
Keyword(s):  
Multiple Myeloma ◽  
Clinical Response ◽  
Bone Pain ◽  
Novel Agents ◽  
Cell Transplant ◽  
Post Transplant ◽  
Opiate Use ◽  
The Impact

Background: Bone pain is one of the most common presentations of multiple myeloma and nearly all patients have skeletal involvement in the course of disease. Consequently, many patients require narcotics for symptom management at the time of diagnosis but the long term impact of MM treatment on pain control remains uncertain. With the advent of combination therapy for MM with novel agents followed by transplant and then maintenance therapy, clinical response is nearly universal and greater than 30% of patients achieve a serologic complete response. Therefore, we examined the impact of modern myeloma-directed therapy and high response rates on the use of narcotics up to 1 year after transplant in this group of patients. Methods: A retrospective review of data collected from the Rutgers-CINJ database was conducted. All patients who received induction inducing therapy (e.g. bortezomib, lenalidomide and dexamethasone or cyclophosphamide, bortezomib and dexamethasone) followed by high dose melphalan and autologous stem cell transplant (ASCT) and who had adequate post-transplant follow up (at least 100 days) were included. Morphine use was assessed at the time of transplant and at follow-up visits. All opiates (e.g. oxycodone, fentanyl, MS contin, etc.) where converted to morphine equivalents/day (ME/day) and recorded. Treatment responses were determined based on the International Myeloma Working Group Response Criteria. We compared the incidence and amount of narcotic use over time using one-way analysis of variance (ANOVA) and Dunn's multiple-comparison test. Results: 189 patients were included in the analysis. 38% were using opiates at the time of transplant. At 100 days post-transplant 35.5% were using opiates and at 1 year post transplant 30.9% were using opiates (p=0.04) . Average opiate use was 74.1 ME/day (95% CI: 55.2 to 92.9), 69.45 ME/day (95% CI: 50.5 to 88.3), and 70.78 ME/day (95% CI: 43.5 to 98) for each of the aforementioned time points (p=0.088) (Figure 1). For example, 74 ME/day would be equal to approximately 50 mg of Oxycodone daily. 74 patients were active opiate users at the time of transplant (Table 1). Response to myeloma treatment (remission, progression, relapse) was not different in opiate-using patients at the time of transplant or at 100 days and 1 year after transplant (Table 2). Conclusion : Early studies from the 1960's reported on the rapid reduction of bone pain in treatment responsive patients with MM (Hogstrata et al.). Recently, treatment modalities for MM have significantly improved, leading to markedly increased remission rates (>90%), progression-free and overall survival. With dramatically increased serologic responses, one would hypothesize that there would be a decline in pain and a subsequent decrease in opiate use. However, in this retrospective chart review we found that 30% of multiple myeloma patients continued to use opiates following transplant and that ongoing use of opiates appeared to be independent of clinical response. Interestingly, at the time of transplant active opiate users had a CR of 27.2% while the non-opiate using patients had a CR of 13.3%. Although there was a slight decline in the number of opiate users at the 1 year follow up, 33% of opiate users continued at their original level of opiate use and 22% increased their opiate use at 1 year post ASCT. Persistent long term use of opiates is of particular concern given that the survival of patients with MM has significantly improved with the use of novel agents and autologous transplant with an increasing number of patients surviving 10 years or more. In patients who have achieved an excellent response (e.g. serologic CR and negative PET scan), ongoing narcotic use should be addressed at each visit and other advanced pain management techniques should be considered. Disclosures No relevant conflicts of interest to declare.

Depth of Response with Stem Cell Transplantation and Outcome for Multiple Myeloma in the Era of Novel Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1228-1228
Author(s):  
David Dingli ◽  
Francesca Gay ◽  
Francis Buadi ◽  
Angela Dispenzieri ◽  
Suzanne R Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Novel Agents ◽  
Cell Transplant ◽  
Time To Progression ◽  
Depth Of Response ◽  
The Impact

Abstract Abstract 1228 Poster Board I-250 Background It is generally believed that a ‘deeper’ response in multiple myeloma is associated with an improved outcome, including time to progression (TTP) as well as overall survival. Before the advent of novel agents such as IMiDs or bortezomib, complete responses (CR) were rare in the absence of stem cell transplantation (ASCT). In that era, the depth of response achieved before ASCT tended to be dwarfed by the impact of the conditioning used for stem cell transplant. Hence, the time to progression in patients achieving CR before ASCT was not different from those who achieved CR after ASCT. With novel agents, CR rates are higher and again raises the question of whether patients who achieve CR before ASCT benefit from consolidation with ASCT. The purpose of this analysis was to determine whether CR achieved before ASCT still benefit when consolidated with ASCT Methods After approval from the Institutional Review Board at Mayo Clinic Rochester, the transplant dysproteinemia database was searched for all patients treated with novel agents and patients who achieved CR before or after ASCT were identified. In addition, we identified patients with IMiDs induction therapy and achieved CR but did not proceed with ASCT. Relevant demographic, clinical and laboratory characteristics were determined at the time of ASCT. Comparisons between groups were performed with non-parametric tests. Overall survival and TTP were determined from the time of ASCT using the Kaplan-Meier method. Results A total of 354 patients who underwent ASCT within a year from diagnosis of multiple myeloma were identified. Of these, 24 achieved CR before proceeding to ASCT while another 100 patients achieved CR after ASCT. There were no differences between the two cohorts with respect to age (58 vs 57.5 yr, p=0.14), gender, number of treatment regimens (1 vs 1, p=0.83), time to ASCT (6.5 vs 6.3 months, p=0.80), b2M (2.41 vs 2.26, p=0.58) and ISS (p=0.23). Patients who achieved CR before ASCT had a lower plasma cell burden (1.0 vs 5.0%, p<0.0001) and lower labeling index (0 vs 0, p=0.0007). Aneuploidy was present in none of the patients with CR before transplant compared to 10% in patients who achieved CR after ASCT (p=0.11). The median TTP for patients with CR before ASCT has not been reached (71% at 70 months) compared to 30 months for patients who achieved CR after ASCT (p=0.07). After a median follow up of 70 months, 21 of 24 patients (88%) with CR before transplant are alive compared to 76 of 100 patients with CR after ASCT (p=0.44). In contrast, for patients who achieved CR with IMiDs but did not proceed with ASCT, 55% have not progressed at 51 months and 71.7% are alive at 51 months (Gay et al ASH, 2009). Conclusion Our results suggest that patients who achieve CR before ASCT benefit from high-dose therapy and experience prolonged TTP without the need for maintenance therapy. ASCT after achieving CR can result in a deeper response with improvement in disease free and overall survival. Disclosures Lacy: celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria.

Increased Incidence of Extramedullary Plasmacytomas In Patients with Multiple Myeloma In the Era of Novel Therapy and Effect of Pomalidomide on Extramedullary Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3047-3047
Author(s):  
Kristen Detweiler Short ◽  
S. Vincent Rajkumar ◽  
Francis Buadi ◽  
Dirk Larson ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Soft Tissue ◽  
Research Funding ◽  
Low Dose ◽  
Novel Agents ◽  
Temporal Area ◽  
Immunomodulatory Agents ◽  
Extramedullary Disease ◽  
Extramedullary Plasmacytomas

Abstract Abstract 3047 Background: There is concern about the increased incidence of extramedullary plasmacytomas among patients with multiple myeloma (MM) in recent years (Varettoni et al Annals of Oncology 21: 325–330, 2010). There is controversy about whether novel agents increase the risk of extramedullary disease (EMD). EMD may be associated with decreased overall survival in MM. The purpose of this study was to determine the incidence of true, treatment-emergent EMD in MM among a cohort of patients who have been previously exposed to novel agent (thalidomide, lenalidomide, or bortezomib) therapy, and to evaluate the activity of pomalidomide in patients with EMD. Methods: We examined 174 consecutive patients with relapsed refractory multiple myeloma that were enrolled on a phase II clinical trial of pomalidomide plus low-dose dexamethasone. The study cohort was chosen since all patients had previously been exposed to novel agents, and were followed systematically. We adopted a strict definition of EMD which required that in order to be considered extramedullary, plasmacytomas must not have risen from any bone. Thus, masses arising from the bone with a soft tissue component were not considered extramedullary. Results: Of 174 patients studied, 16 patients (9.2%) had EMD prior to enrollment. In 3 of the 16 patients, EMD was present at time of diagnosis and was therefore not considered as treatment-emergent disease for this analysis. In 13 of 174 patients (7.5%) EMD developed during the course of MM, after starting therapy. All 13 patients by inclusion criteria were exposed to novel agents prior to the onset of EMD, including 100% to immunomodulatory agents (thalidomide or lenalidomide); and 78% (10 patients) were exposed to bortezomib prior to developing EMD. The median number of lines of prior therapy in these patients was 6, range 1–12). EMD occurred a median of 48 months following diagnosis (range, 16–183 months); the rate of EMD in the first 3 years following diagnosis of MM was 3%. Since all patients had prior exposure to immunomodulatory agents in this cohort, we were able to calculate the median length of time from initiation of immunomodulatory agents to onset of EMD as 24 months (range 7–119 months). The EMD sites involved included the temporal area soft tissue (3), muscle (3 [1 pt with 10 different areas of involvement, 1 pt with 5 muscles involved]), chest wall not attached to bone (3), abdominal/pelvic masses (3), kidney (2), scrotum (2), sinus (1), paraspinal (1), hilar/pleural based (1), paraesophageal (1), subcutaneous tissue (1), pancreas (1), spleen (1), mediastinum (1), pleural fluid (1), liver (1). Per protocol, all patients received pomalidomide (2-4 mg per day) and low dose dexamethasone (40 mg once a week). Of the 13 patients, there were 2 CR (with complete disappearance of EMD), 2 PR, 2 stable disease, 3 with progressive disease, and 4 patients who did not have their EMD re-evaluated. Thirty percent (n=4) of patients had a 50% or greater reduction in size of the EMD including one patient who received concomitant radiation. Overall survival from measured from trial entry was significantly shorter for patients who presented with EMD compared to those who did not have EMD, median 16 months versus not reached, p=0.002 (log-rank). Conclusion: We found that 7.5% of patients with relapsed refractory myeloma in the era of novel agents develop EMD during the course of their myeloma, including 3% within 3 years of diagnosis. The underlying reasons for the possible increased incidence of EMD may include better radiographic detection (the role of PET/CT scans and MRI), improved overall survival of patients in recent years, and the possibility that novel agents may increase the risk for strictly defined, true EMD among patients who did not have EMD at time of initial MM diagnosis. These need further study. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

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