scholarly journals Multiple myeloma: Unveiling the survival data with different lines of treatments

2022 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Suja Abraham ◽  
Helan Kurian ◽  
Arpith Antony ◽  
JeevaAnn Jiju ◽  
Timy Thomas
Keyword(s):  
Multiple Myeloma ◽  
Survival Data

Thalidomide-Dexamethasone Versus Melphalan-Prednisolone as First Line Treatment in Elderly Patients with Multiple Myeloma: An Interim Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 782-782 ◽  
Author(s):  
Heinz Ludwig ◽  
Johannes Drach ◽  
Elena Tóthová ◽  
Heinz Gisslinger ◽  
Werner Linkesch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Interferon Alpha ◽  
Survival Data ◽  
Response Rate ◽  
Skin Toxicity ◽  
Thromboembolic Complications ◽  
Interferon Alpha 2B ◽  
Best Response ◽  
Present Trial

Abstract Thalidomide-Dexamethasone (TD) is an active regimen in patients with relapsing/refractory multiple myeloma (MM). Recent phase II and III studies revealed an even higher response rate in previously untreated patients. In the present trial we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly patients with multiple myeloma. The trial is designed to include 350 pts with MM, 190 patients have been enrolled so far (median age: 72 years, stage I: 9 (5%), stage II: 61 (32%), stage III: 120 (63%). Patients are randomized to Thalidomide 200mg/day and Dexamethasone 40mg, days 1–4 and 15–18 (on odd cycles) and days 1–4 (on even cycles) or Melphalan 2.5mg/kg day 1–4 and Prednisone 2mg/kg days 1–4, q 4–6 weeks. Thalidomide should be dosed up to 400mg/day, if feasible. Patients achieving response or stabilization are randomized to maintenance treatment either with Thalidomide (maximal dose 200mg/day)-Interferon alpha-2b (3Mega U, TIW) or Interferon alpha-2b (3Mega U/TIW). All patients are scheduled for monthly Zometa (4mg) during the entire period. Response is defined according Blade’s criteria, statistical results are given by intend to treat analysis. 125 patients are evaluable for response as yet. Best response to TD was: CR 6 (10%), NCR 7 (12%), and VGPR 9 (15%) PR 9 (15%), MR 10 (16%) yielding an ORR of 67%. Four pts had SD (7%) and 16 PD or failure (26%). The respective results in pts on MP were: CR 2 (3%), NCR 4 (6%), VGPR 5 (8%), PR 13 (20%), MR 7 (11%), ORR 48% (p<0.05). Analysis per protocol revealed an ORR of 89% in the TD and 66% in the MP group (p<0.02). Time to response and time to best response was significantly shorter in the TD (8, 11 weeks, respectively) compared to the MP group (10, 39 weeks, respectively; p<0.01, p<0.0047, respectively). Due to the interim nature of the analysis, survival data will be presented only for both groups combined at the meeting. Grade III-IV thrombocytopenia was more frequent and leucopoenia was statistically significant more common in pts on MP (4 (7%) vs. 1 (2%); ns. and (8 (13%) vs. 1 (2%); p< 0.05, respectively). Patients on TD had more grade II-III neuropathy 15 (25%), psychological toxicity 12 (20%) and, skin toxicity 7 (12%) compared to those on MP (5 (8%), 5 (8%), 3 (3%), respectively). Thromboembolic complications were seen in 5 (8%) pts on TD and in 2 (3%) on MP. In conclusion, time to response and time to best response was significantly shorter in pts on TD. Both, the intend to treat and per protocol analysis showed a higher response rate in TD treated pts (67% vs. 48%, p<0.05 and 89% vs. 66%, p<0.02, respectively). Leucopoenia was more frequent in pts on MP and neuropathy more common in TD treated pts. There was a tendency for increased incidence of thromboembolic complications, psychological disturbances and skin toxicity in pts on TD. In relation to the high median age (72 years) of pts studied, TD was well tolerated.

Clinical Significance of the Tumor Suppressor p53 Codon 72 Polymorphic Variants in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5102-5102
Author(s):  
Natalia C. Gonzalez-Paz ◽  
Wee Joo Chng ◽  
Shaji Kumar ◽  
Tammy Price-Troska ◽  
Scott Van Wier ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Suppressor ◽  
Plasma Cell ◽  
Survival Data ◽  
Clinical Manifestations ◽  
Cellular Transformation ◽  
Response To Treatment ◽  
Codon 72 ◽  
Number Of Patients ◽  
Polymorphic Variants

Abstract Background: The p53 tumor suppressor gene has a common sequence polymorphism that results in either proline or arginine at amino-acid position 72. The Pro72 and Arg72 variants have been reported to differ in its functional activity. The Arg72 variant induces apoptosis more efficiently than Pro72 variant by its greater ability to localize to the mitochondria and increase the release of cytochrome c into the cytoplasm. In addition, recent studies have demonstrated that Arg72 variant was a better suppressor of cellular transformation, an activity believed to rely on the pro-apoptotic function of p53. Moreover, the Pro72 variant has been associated with a higher incidence of tumors. Aim: To evaluate the effect of the polymorphic variants of codon 72 and clinical outcome in patients with plasma cell malignancies. Patients and Methods: We analyzed 79 patients with plasma cell malignancies seen at Mayo Clinic between 2000 and 2003. Genomic DNA was extracted from CD138+ sorted plasma cell from bone marrow aspirates. PCR amplification of codon 72 and posterior sequencing was used for the analysis. Results: A total of 79 patients were analyzed. Thirty-four patients (34%) were heterozygous for p53, 57 (59%) homozygous for Arginine and 6 (6%) homozygous for Proline. The distribution among disorders was as follow, 52 patients had MM, 14 patients with SMM and 13 with MGUS. Among patient with MM 25% were Pro/Arg heterozygous, 71 % were Arg/Arg homozygous and 3.8% Pro/Pro homozygous. Survival data among MM patients and genotype were analyzed to Kaplan- Meier method. No significant differences were found among patients who carried homozygous (72R) or heterozygous genotype and overall survival. We exclude the analysis in MGUS and SMM for a low number of patients available. Conclusions: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with Multiple Myeloma, but further study is needed to assess whether this polymorphism is associated with progression of MGUS to MM, age of onset, clinical manifestations, response to treatment etc.

Survival gains in multiple myeloma from 2003 to 2014.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 98-98
Author(s):  
Rafael Fonseca ◽  
Anupam B. Jena ◽  
Desi Peneva ◽  
Zoe Clancy
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Treatment Options ◽  
The United States ◽  
Novel Therapies ◽  
Full Sample ◽  
The Past ◽  
Improvement In Survival ◽  
Second Wave ◽  
Novel Agent

98 Background: Survival probabilities for patients with multiple myeloma have increased considerably over the past several decades, and a conservative estimate of 5-year survival today is approximately 50%, perhaps higher with optimal treatment. Treatment options for multiple myeloma have grown significantly beginning in 2003 with the approval of bortezomib, followed by approvals for lenalidomide and thalidomide in 2006. The second wave of novel agent approvals began in 2012 with carfilzomib, followed by pomalidomide in 2013. The aim of this study was to estimate the survival gains associated with multiple myeloma therapies after the introduction of novel therapies beginning in 2003 in the United States. Methods: We estimated survival gains for multiple myeloma patients diagnosed in the 5-year period from 2010-2014—who had access to newer therapies like lenalidomide, bortezomib, pomalidomide, and carfilzomib—compared with patients diagnosed in the 5 years prior to the approval of bortezomib (1998–2002). We used data from the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry and a generalized gamma regression survival model. The sample from SEER included patients aged > 18 years who had a diagnosis of multiple myeloma between 1983 and 2014. Results: Of 88,462 patients identified in the full sample, 14,446 patients were diagnosed in 1998–2002 and 25,948 patients were diagnosed in 2010–2014. Overall survival was 51% longer ( P< 0.001) in multiple myeloma patients diagnosed in 2010–2014 than in patients diagnosed in 1998–2002. Patients diagnosed in 2010–2014 had median and mean survival of 1.32 and 2.27 years longer, respectively, than patients diagnosed in 1998–2002. Conclusions: Patients diagnosed with multiple myeloma during 2010–2014 had significant improvement in survival relative to patients diagnosed in 1998–2002. This study found continued improvement in survival in multiple myeloma patients in the most recent 5-years of survival data available, demonstrating the considerable progress made since the wave of multiple myeloma innovation began in 2003.

Multiple Myeloma in the Afro-Caribbean Inner City Population: Conventional Cytogenetics and Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5710-5710
Author(s):  
Dhvani Thakker ◽  
Charles Yun ◽  
Adam Goldrich ◽  
Helzner Elizabeth ◽  
Daniel Fein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Logistic Regression ◽  
Survival Data ◽  
Poor Prognosis ◽  
Regression Models ◽  
Chromosome Banding ◽  
Newly Diagnosed ◽  
Cytogenetic Abnormalities ◽  
Logistic Regression Models ◽  
Adjusted Logistic Regression

Abstract Background: Multiple Myeloma (MM) is the second most common hematologic malignancy in the United States. African Americans have among the highest risks of MM and MGUS with several distinct features compared to existing literature. Furthermore, the prevalence of MM is even higher in the Afro-Caribbean population. Cytogenetic and molecular genetic abnormalities predict outcome in patients with MM. Hyperdiploid MM (H-MM) generally has a better prognosis than nonhyperdiploid MM (NH-MM). In addition, patients with additional chromosome 1 abnormalities, loss of chromosome 13, translocation t(14;16) and t(4;14) tend to have a worse survival while patients with translocations t(11;14) are associated with improved survival. In our patient population, the most common cytogenetic abnormalities and their effect on survival remain unknown. Objective: This study was performed to establish a profile of Afro-Caribbean patients with newly diagnosed Multiple Myeloma in order to gain further insight into unique cytogenetic abnormalities and their effects on survival. Methods: Patients with Multiple Myeloma at Kings County Hospital Center and University Hospital at Brooklyn from 2000-2013 were identified by our tumor registries (n=311). We included all the newly diagnosed patients from 2000-2013 who underwent a bone marrow biopsy and conventional cytogenetic by chromosome banding and FISH (n= 173). Patients who did not have a cytogenetic analysis were excluded. Data was collected at the time of initial presentation to include demographics and cytogenetic abnormalities. Survival data was obtained from Social Security Death Index. Differences in frequency of each cytogenetic abnormality by mortality status were examined using Chi-Square or Fisher’s Exact Tests. Two sets of age-adjusted logistic regression models were used to examine potential cytogenetic correlates of both poor (less than two years) and good (4 years or more) survival. Data analysis was performed using SPSS Advanced Statistics. Results: The median age at the time of diagnosis was 65 (Range 36-90). Chromosome banding and FISH showed abnormal cytogenetics in 46% of our patients (n=79). These patients were also found to have multiple abnormal clones. NH-MM was found in 24% (n=19) and H-MM was found in 39% (n=31) of the 79 patients. The most commonly affected abnormalities were trisomiesof odd-numbered chromosomes; +1 (47%), +3 (19%), +5 (21%), +7 (24%), +9 (47%), +11 (42%), +15 (44%), +17 (9%) and +19 (29%). Thirty five percent of 173 patients have expired (n=60). The median survival in the deceased patients was 6.2 years (Range 0.34-12.9). When we examined all patients who lived greater than four years post-diagnosis (n=152), we found significant abnormalities including +5 (p=0.052), NH-MM (p=0.009) and t(11;14) (p=0.03) (See Table 1). Indicators of poor prognosis including 1q gain (p=0.13), loss of chromosome 13 (p=0.21) and del17 (p=0.08) were not significant. In patients who are living, 19% (n=29) have not yet reached the four-year post-diagnosis survival. Less than ten percent underwent autologous stem cell transplantation. Excludes patients who lived less than 3 months post diagnosis August 5 2014 Table 1: Age-Adjusted Logistic Regression Models Predicting Good Survival (lived 4 years or more post-diagnosis) Chromosome abnormality ( + gain, - loss) Age-Adjusted Odds Ratio (95% CI) N=152 P-value 1+ 0.77 (0.26, 2.29) 0.63 1- 2.91 (0.58, 14.57) 0.19 3+ 1.05 (0.35, 3.17) 0.93 5+ 0.47 (0.22, 1.00) 0.052 7+ 0.39 (0.14, 1.10) 0.08 11+ 0.80 (0.36, 1.75) 0.57 14+ 2.07 (0.62, 6.91) 0.24 15+ 0.74 (0.34,1.60) 0.44 19+ 1.20 (0.46, 3.13) 0.71 X- 0.42 (0.11, 1.50) 0.18 Y- 0.40 (0.13, 1.26) 0.12 Hyperdiploidy 0.88 (0.39, 2.00) 0.88 Nonhyperdiplody 0.24 (0.08, 0.70) 0.009 t(4;14) 0.76 (0.27, 2.15) 0.60 t(11;14) 0.18 (0.04, 0.86) 0.03 Conclusion: In this group of Afro-Caribbean patients, median survival (6 years) was higher than Surveillance, Epidemiology, and End Results (SEER) data and more recent review of literature. Gain of chromosome 5 and t(11;14) are consistent with existing data for good prognosis. However, NH-MM which is usually an indicator of poor prognosis was also highly significant in the four-year post-diagnosis survival. This further supports the notion that prognostic value of cytogenetic analysis in this population requires further exploration. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes of Patients with Multiple Myeloma Harboring Gain/Amplification 1q in the Era of Modern Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-46
Author(s):  
Xiao Hu ◽  
Cherng-Horng Wu ◽  
Janet Cowan ◽  
Raymond L. Comenzo ◽  
Cindy Varga
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Research Funding ◽  
The United States ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Rank Tests ◽  
Treatment Regimens ◽  
The Impact ◽  
Log Rank Tests

Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States. Fluorescence in-situ hybridization (FISH) is a popular tool to detect cytogenetic alterations which in turn, can contribute to the risk stratification of patients with MM. Gain or amplification of CKS1B gene at chromosome 1q21 region (gain 1q) is detected in 35-40% of newly diagnosed MM cases, and has been reported to be associated with inferior prognostic outcomes. It also frequently occurs with the deletion of CDKN2C at chromosome 1p32.3 (del 1p). There is a distinct lack of data on patients harboring this cytogenetic alteration in the era of novel agents. We sought to look at outcomes of this patient population at a single institution over the last 5 years. Methods: This retrospective study included all patients with MM as defined by the International Myeloma Working Group (IMWG) with available FISH studies identifying gain 1q between 01/01/2015 to 04/30/2020 at Tufts Medical Center. The study was approved by the Institutional Review Board. Baseline demography, disease characteristics, and treatment history were extracted from the electronic medical records. With death as primary event, overall survival (OS) was defined as the survival time from the discovery of gain 1q to death. Progression free survival (PFS) was defined as the time from discovery of gain 1q to first progression/relapse or death, whichever occurred first. Kaplan-Meier method was used to estimate survival data. Differences in survival between two groups were analyzed by log-rank tests. Multivariable cox regression adjusting for baseline characteristics and significant concurrent cytogenetic alterations were performed to explore the impact of treatment regimens on survival. Results: Of the forty-nine subjects included in this study, the age range was 39 to 85 years; 31 patients (63.3%) were over the age of 65 years, and 28 (57.1%) were male. Twenty-eight (57.1%) subjects with gain 1q were newly diagnosed while the remaining 21 (42.9%) were identified at relapse. Gain 1q was present in more than 20% of clonal cells in 73.5% of subjects and 29.6% had del 1p as well. Patients with gain 1q were more likely to have deletion 13q (65.3%) and hyperdiploidy (61.2%). Regarding treatment, 75.7% of patients received bortezomib, 70.3% received lenalidomide, 38.9% underwent autologous stem cell transplant (ASCT) and 64.9% received daratumumab. At the time of analysis, 41 patients were still alive. For the entire cohort, the estimated median OS was not reached (NR) (95% confidence interval [CI], 24.1-NR), and the estimated median PFS was 15.27 months (95% CI, 4.77-NR). In log-rank tests, presence of extra medullary disease was associated with shorter PFS (4.8 vs 24.1 months, P=0.003), while IGH abnormalities including complex IGH rearrangements or losses were associated with longer PFS (NR vs 8.2 months, P=0.046). Lenalidomide-based treatment was associated with prolonged OS (NR vs 17.2 months, P=0.048). Bortezomib-based therapy and upfront ASCT were associated with improved PFS (15.3 vs 4.7 months, P=0.036; NR vs 4.8 months, P =0.019 respectively). Further multivariate analyses adjusting for age, number of CKS1B copies, International Staging System stage, baseline creatinine, clone size, del 1p, lactate dehydrogenase, extra medullary disease, and IGH abnormalities revealed that administration of daratumumab after the discovery of gain 1q was associated with superior OS (Hazard Ratio [HR]=0.023x10^-2, 95% CI [0.002x10^-4, 0.299], P =0.022) compared with those not receiving this agent; both the use of bortezomib (HR=0.210, 95% CI [0.064, 0.687], P =0.010) and daratumumab (HR=0.126, 95% CI [0.015, 1.036], P =0.054) were associated with prolonged PFS. The use of lenalidomide or upfront ASCT lost prognostic benefit after adjusting for additional variables in multivariate models. Conclusions: The outcomes of MM patients with gain 1q were evaluated according to clinical characteristics, concurrent chromosomal alterations and treatment regimens. In our small cohort, daratumumab and daratumumab-bortezomib combination regimens were found to have a favorable impact on survival. Future prospective clinical trials with larger sample sizes are warranted to confirm the results and further improve the outcomes of MM patients with this cytogenetic alteration. Disclosures Comenzo: Amgen: Consultancy; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Prothena: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding.

Response to Salvage Therapies and Outcome of Patients with Multiple Myeloma Relapsing After Pomalidomide Therapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1965-1965
Author(s):  
Shirshendu Sinha ◽  
Shaji Kumar ◽  
Suzanne Hayman ◽  
Francis Buadi ◽  
Kristen Detweiler Short ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Survival Data ◽  
Research Funding ◽  
Phase 2 ◽  
Treatment Regimens ◽  
Phase 2 Clinical Trial ◽  
Study Population ◽  
Ongoing Phase

Abstract Abstract 1965 Background: Pomalidomide is an immunomodulatory compound to be used for heavily pre-treated patients with relapse and refractory multiple myeloma and has shown considerable efficacy in recent clinical trials. It is not clear how patients may respond to other therapies, once the disease becomes refractory to pomalidomide. We examined this question among a cohort of patients receiving pomalidomide therapy in phase 2 clinical trials. Methods: Patients enrolled in an ongoing phase 2 clinical trial of pomalidomide (2-4 mg daily) along with dexamethasone (40 mg weekly), in relapsed myeloma, form the study population. Several cohorts of patients (>= 3 prior therapies not specified, lenalidomide refractory, and lenalidomide and bortezomib refractory patients were enrolled sequentially in this trial (Lacy, M.Q., et al., J Clin Oncol, 2009. 27(30): p.5008–14). Only those patients who have gone off study for disease progression were included in the current analysis. Details of subsequent therapies and survival data were obtained from the medical records. Results: Forty-seven patients from among 142 patients enrolled on the clinical trial between November, 2007 and April, 2010 were included in the study. The median (range) duration of pomalidomide therapy was 4 (0.6-16) months. 15 (32%) patients were lenalidomide refractory and 11 (23%) were refractory to both lenalidomide and bortezomib at the time of study entry. The best confirmed response to pomalidomide was MR (Minimal Response) or better in 23 patients (52%). Various regimens were employed following relapse on pomalidomide. The response to the first regimen following relapse in the 34 patients where salvage therapy was initiated is as shown in Table 1. Overall, 81 regimens were employed across 34 patients; median (range) number of regimens per patients was 1 (0-8). The response rates to the different regimens were as shown in the Table 1. The median overall survival (OS) from the time of progression on pomalidomide was 14.7 months (95% CI; 4, NR). The OS was similar between those patients who had a response to pomalidomide (MR or better) and those who did not. However the OS was shorter for patients who were refractory to lenalidomide and bortezomib (2.1 months) compared to those who were lenalidomide refractory only (6.5 months), and the non-refractory group (NR), P=0.06. Conclusions: This study confirms poor outcome of the patients relapsing after all available therapies. It also gives interesting insights into the activity of different regimens among patients who have relapsed after pomalidomide. The findings once again highlight the incurable nature of the disease and warrant further investigation to develop newer effective treatment regimens for this group of patients who presently do not have effective therapeutic options especially in the relapsed setting. Regimens: ASCT: Autologous Stem Cell Transplantation, Bz: Bortezomib, Mel=Melphalan, Dex: Dexamethasone, CRD: Cyclophosphamide, Revlimid (Lenalidomide), Dexamethasone, CTX; Cyclophosphamide, Len; Lenalidomide, Sor: Sorafenib, VDT-PACE: Velcade (Bortezomib), Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide. Response: SD; Stable Disease; Prog; Progression MR: Minimal Response; PR: Partial Response. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Mikhael:Celgene: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.

Incorporation of Bortezomib Into Frontline Treatment of Multiple Myeloma According to Risk Stratification Shifts the Most Significant Prognostic Indicator From Cytogenetics to the Quality of Induction Response

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3056-3056
Author(s):  
Daryl Tan ◽  
Bernard K.C Yap ◽  
Lionel K.Y See ◽  
Grace Kam ◽  
Colin Phipps Diong ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Induction Therapy ◽  
Survival Data ◽  
Hazard Ratio ◽  
Significant Prognostic Factor ◽  
Cell Transplant ◽  
Term Survival ◽  
Number Of Patients

Abstract Abstract 3056 Introduction: Multiple myeloma (MM) is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several adverse features of MM, it has been incorporated into the induction algorithms of high-risk MM. We evaluate the survival data of MM patients managed in a single institution, overall, and with respect to treatment eras before (era 1) and after (era 2) the incorporation of bortezomib as frontline therapy for high-risk MM. Methods: From a comprehensive MM registry maintained in a tertiary institution, we study the survival data of 304 consecutive and previously untreated MM patients managed at our institution from 2000 to 2009. For induction therapy, transplant-eligible patients received. VAD chemotherapy from 2000 to 2004, and thalidomide/dexamethasone (thal/dex) combination from 2004 to 2009. Transplant-ineligible patients received VAD chemotherapy, thal/dex or melphalan/prednisolone (MP) combination from 2001 to 2004, and thal/dex or MP/thalidomide combination from 2004 to 2009. Patients < 65 years were eligible for high-dose therapy with autologous stem cell transplant (HDT/ASCT). Bortezomib became available for treatment of relapsed disease from 2004 and was incorporated into induction therapy in selected patients with high-risk MM from 2006. High-risk MM is defined by presence any adverse factors including stage III on the International Staging System (ISS), deletion 13, hypodiploidy, pseudo-diploidy or near-tetraploidy on metaphase karyotyping, or presence of deletion 17p, t(4;14) or t(14;16) on interphase florescence in-situ hybridization (FISH). As FISH was only available from 2004, the results of FISH will not be included in the survival analysis. Patient and disease characteristics, and survival data were evaluated overall, and with respect to treatment eras. Disease response was assessed by the IMWG criteria after induction treatment and after HDT/ASCT for transplant ineligible and eligible patients respectively. We applied multivariate Cox's regression modeling to determine what baseline parameters, along with the eventual induction response, significantly affected the OS in the respective eras. Results: The median age of all patients was 62 years. Overall, 35%, 40% and 25% of patients presented with ISS stages I, II and III respectively. Conventional karyotyping detected abnormalities in 49% (del 13 [17%], hypodiploidy [18%], hyperdiploidy [22%], pseudodiploidy [7%] and near tetradiploidy [2%]) of patients. Overall, the ISS, conventional cytogenetics, age (≤ or > 60 years), the presenting platelet count (≤ or > 140 × 109/L) and the induction response attained were discriminating of the overall survival (OS) (median= 5.2 yrs) on univariate analyses. Patients and disease characteristic and number of patients undergoing HDT/ASCT were comparable between the 2 eras. 33% of patients in era 1(N=182) were exposed to bortezomib predominantly in the relapse setting, while 52% (41% upfront, 59% during relapse) of patients were exposed to bortezomib (N=123) in era 2. Number of patients attaining ≥ very good partial response (VGPR) were significantly higher in era 2 compared with era 1 (48% vs 26%, p<0.001). The median OS of patients in era 1 and 2 were 5.1 and 6.0 respectively (P=0.06). On multivariate analysis stratified by era, the presence of an abnormal non-hyperdiploid karyotype was the most significant prognostic factor in predicting a worse outcome in era 1(median OS 2.7 years, hazard ratio 3.4, p=0.02), while the attainment of ≥VGPR emerged as the single most significant factor in predicting a favorable outcome in era 2 (median OS 8.1 years, hazard ratio 0.01, p<0.001). Conclusion: Our study suggests that bortezomib use in the frontline, rather than relapse setting may be better able to overcome the effects of adverse cytogenetics. Superseding the adverse effects of all other presenting clinical and laboratory parameters, the attainment of ≥VGPR emerged as the single most significant predictor of long-term survival in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.

High-Dose Cyclophosphamide Is An Effective Salvage Therapy for High-Risk Multiple Myeloma Refractory to New Biological Agents

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5041-5041
Author(s):  
Guillermo L Rivell ◽  
Robert K Stuart ◽  
Luciano J Costa
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Survival Data ◽  
Salvage Therapy ◽  
Conflicts Of Interest ◽  
Biological Agents ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Hsc Transplantation

Abstract Abstract 5041 Background: Novel biological agents, particularly bortezomib (B) and the immunomodulatory agents thalidomide (T) and lenalidomide (L), have improved the response rates and the survival in multiple myeloma (MM). However, patients refractory to, or progressing after, treatment with one or more new agents have a very poor prognosis. Alkylating agents are often avoided in the initial management of MM patients who are eligible for autologous hematopoietic stem cell (HSC) transplantation due to concerns for impairment of HSC mobilization. We hypothesized that high doses of cyclophosphamide (HiCy) administered without HSC support may be an effective and safe treatment to rescue patients with relapsed or refractory MM previously treated with novel biological agents. Methods: We performed a retrospective single institution review of all recent patients receiving high dose cyclophosphamide (3000mg/m2) after failure of one or more new biological agents. Data extracted included patient demographics, disease characteristics, treatment history, toxicity, response, and survival data. This study received institutional review board approval. Results: Between 03/2009 and 06/2010, 11 patients were treated with cyclophosphamide 3,000mg/m2 for relapsed or refractory MM. Supportive care included administration of mesna to prevent hemorrhagic cystitis and PEG-filgrastim to minimize the duration and depth of neutropenia. All patients received antibiotic prophylaxis with ciprofloxacin, acyclovir, and fluconazole. The median age of patients was 52 years (range 26–73). Among these, 7 patients (64%) had stage 2 (international staging system), and 4 patients (36%) had stage 3 disease. Metaphase cytogenetics and/or fluorescence in situ hybridization (FISH) was available for 10 patients. In all but one patient, MM cells had FISH abnormalities. Cytogenetic subgroups included five cases with complex karyotype, 6 cases with a deletion of chromosome 13, 3 cases with abnormalities involving 17p, 2 cases with t(11;14), 2 hyperdiploid cases, and 1 case with t(14;16). The median number of prior treatments was 3 (range 1–6) with two patients previously receiving autologous HSC transplantation. All patients were refractory to the last therapeutic regimen and had failed to respond or were refractory to a regimen containing B. Seven patients had also previously received an immunomodulatory agent (2 patients received T and 6 patients received L). At the time of treatment 5 patients had plasma cell leukemia and 5 patients had renal failure (including 2 patients on dialysis). All patients developed grade 4 neutropenia, and 9 patients developed thrombocytopenia requiring transfusion support. Six patients (55%) developed fever and neutropenia requiring intravenous antibiotics, and one patient (9%) had documented bacteremia. One patient died from sepsis 7 weeks after cyclophosphamide treatment. Median follow up was 13.4 weeks (range 4.4–69.7) from HiCy administration. Overall, 7 patients had a partial response or better (64%), including 3 patients with a very good partial response (27%). Four of the 7 responding patients subsequently underwent autologous (3) or allogeneic (1) HSC transplantation. Median overall survival was not reached, and the estimated one year survival was 52.5% (+/− 20.4%). Conclusion: High-dose cyclophosphamide can be an effective salvage therapy for young, high-risk MM patients refractory to new biological agents. HiCy is associated with significant toxicity, and careful patient selection is necessary. Disclosures: No relevant conflicts of interest to declare.

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