Multiple Myeloma In Patients Under 40 Years Old Is Associated With High-Risk Features and Worse Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5359-5359 ◽  
Author(s):  
Caitlin L. Costello
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Young Patients ◽  
Age At Diagnosis ◽  
Cancer Center ◽  
Common Disease ◽  
High Dose

Background The median age of patients diagnosed with multiple myeloma (MM) is approximately 70 years old. It is an uncommon malignancy in persons younger than 40 years, representing only 2% of all patients diagnosed with MM. It has been suggested that young patients may present with more aggressive and less common disease features, frequently delaying the initial diagnosis and thereby affecting outcomes. With this background, we explored the outcome of young MM patients presenting to our institution over the past thirteen years. Methods We performed a retrospective review of a cohort of 236 patients with MM who received treatment for active MM at the University of California, San Diego Moores Cancer Center between January 2000 and July 2013.  The demographics and disease features of patients up to 40 years of age at diagnosis were analyzed using descriptive statistics. The survival outcomes of these young patients were compared with the remainder of the cohort using the Kaplan-Meier method. Results Nineteen (6.5%) out of the 236 patients with MM were ²40 years of age at diagnosis, with a median age of 35.5 years old. The median follow-up of this group of young patients was 42 months (range 5-92). The patient and disease characteristics are outlined in Table 1. Seven young patients (37%) had MM with no heavy chain component, including light chain only secreting or non-secretory disease.  Seven patients (37%) had a non-IgG paraprotein. Nine (56%) patients presented with extramedullary plasmacytomas. Two (10%) patients had plasma cell leukemia. All patients received at least one treatment regimen that included a novel agent. Fifteen patients (79%) had received high-dose therapy, and four patients (21%) underwent allogeneic stem cell transplantation (SCT) after at least one prior autologous SCT. The 5-year and 7-year overall survival (OS) from diagnosis was 51.7% and 28%, respectively, and the median OS was 60.7 months. In contrast, the median OS of patients ≥41 years old at diagnosis was 78.6 months (p=0.15, figure 1). Conclusion In this single center study with long follow up, we demonstrate that patients diagnosed with MM ²40 years of age exhibit several high-risk features and frequently present with advanced stage disease. Despite the use of novel agents in this population, there is a statistical trend towards a worse outcome with an 18-month difference in median overall survival when compared to older patients with MM. More aggressive treatment strategies are needed to improve survival in this young patient population. Disclosures: No relevant conflicts of interest to declare.

Impact of t (11;14) on the outcome of autologous hematopoietic cell transplantation (Auto-HCT) in multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Koji Sasaki ◽  
Gary Lu ◽  
Chitra Hosing ◽  
Uday R. Popat ◽  
Sairah Ahmed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Cancer Center ◽  
Induction Treatment ◽  
High Dose ◽  
Significant Difference ◽  
The Impact

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%, <PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.

scholarly journals Autologous Hematopoietic Cell Transplantation in Patients with Multiple Myeloma: IMPACT of Age

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3456-3456 ◽  
Author(s):  
Binod Dhakal ◽  
Ariel Nelson ◽  
Guru Subramanian Guru Murthy ◽  
Raphael Fraser ◽  
Daniel Eastwood ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Age Groups ◽  
Young Patients ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Cell Transplant ◽  
Two Age Groups

Abstract Background: In both the novel and pre-novel agents era, high dose therapy followed by autologous hematopoietic cell transplant (AHCT) has been shown to prolong survival in multiple myeloma (MM) in randomized trials, but prospective have only included younger patients (65 -70 years and younger). Given that the median age at diagnosis of MM is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, the definite outcomes of AHCT in very young patients (<50 years) is also lacking as they represent a very small proportion in clinical trials. Methods: We analyzed a consecutive cohort of patients with MM receiving ASCT from 2000-2015 in two different age groups, old (>70 years; N=105) and young (≤50 years, N=86) and compared the outcomes. The primary objectives were to assess overall survival (OS), progression free survival, (PFS), and non-relapse mortality (NRM) in these two groups. Results: Eighty-sex patients were young (≤50 years), while 105 patients were old (>70 years). Young patients had better performance status and lower co-morbidity index, while majority of older cohort received dose reduced high dose melphalan between 140-180 mg/m2. Median follow up of survivors in the younger cohort was 33 months (range, 2-164) compared to the 22.5 months (3-133) in the old group (p=0.02). The PFS at 1 year was 60% (95%CI 46-72) for young patients and 58 (95%CI, 45-69) for the old ones. The OS at 1 year was 92% (95% CI 84-96) for younger and 85% (95% CI 76-91) for the older cohorts. On multivariate analysis, age did not have any effect on survival (p =0.82), high-risk cytogenetics (HR 2.2, 95% CI 1.06-4.6, p=0.04) was associated with higher mortality. High-risk cytogenetics (HR 1.2, 95% CI 1.1-3.5, p=0.004) and non-responding or progressive disease at transplantation (HR, 5.0 95% CI 1.8-13.5, p=0.02) were significantly associated with inferior PFS. Conclusion: Age by itself should not be a limiting factor in considering the modality of AHCT. However consideration could be given to augmenting therapy for young patients with additional novel treatments post transplant given their similar outcomes with the old patients based on our study. Overall survival between the two age groups, 1: >70 years old and 2: ≤50 years old. Overall survival between the two age groups, 1: >70 years old and 2: ≤50 years old. Figure Figure. Disclosures Hamadani: Takeda: Research Funding. Hari:Merck: Research Funding; BMS: Honoraria.

Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1227-1227
Author(s):  
Nina Shah ◽  
Khawaja Fraz Ahmed ◽  
Sofia Qureshi ◽  
Jatin Shah ◽  
Robert Z Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Chromosomal Abnormalities ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

Codon 72 Polymorphism Of TP53 Gene Is a Novel Prognostic Marker For Thalidomide Therapy In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1891-1891
Author(s):  
Yutaka Hattori ◽  
Yurika Ikeda ◽  
Yuya Suzuki ◽  
Daiju Ichikawa ◽  
Maiko Matsushita
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Prognostic Marker ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Tp53 Gene ◽  
Codon 72 ◽  
Codon 72 Polymorphism ◽  
Significant Difference

Abstract Backgrounds and purpose Recently, newly developed drugs such as thalidomide, lenalidomide and bortezomib have significantly improved survival of the patients with multiple myeloma (MM). However, certain group of the patients who have characteristic high-risk cytogenetic changes such as deletion of TP53 tumor suppressor gene revealed significantly shorter survival. In patients with deletion of TP53 gene, the somatic point mutation in the residual TP53 gene has been reported to be rare. Thus, the exact role of alteration of TP53 gene in high-risk myeloma remains unclear. Polymorphism of TP53 gene at codon 72 in exon 4, CGC to CCC transition, leads to arginine (Arg) to proline (Pro) amino-acid substitution. Biological analyses showed that the Arg variant more efficiently induces expression of P21 and apoptosis via Ser-6 and 20 phosphorylation of p53 protein. In contrast the Pro variant is less resistant to MDM-2-mediated degradation and more potently induced cell-cycle arrest and DNA damage repair. Recently, clinical significance of this polymorphism has been extensively studied in solid tumors as well as hematological malignancies including non-Hodgkin lymphoma and leukemia. However, consistent association of the polymorphism with cancer risk has not been elucidated. The purpose of this study is to examine codon 72 polymorphism in patients with refractory multiple myeloma (MM) treated with thalidomide, and to elucidate its association with myeloma risk and outcome of thalidomide-therapy. Patients & methods A total of 37 Japanese patients with refractory or relapsed MM who were treated with thalidomide monotherapy were included in this study. Three cases showed deletion of TP53 gene by fluorescence in situ hybridization (FISH) analyses. The codon 72 polymorphism was evaluated in the rest of 34 patients. Genomic DNA was isolated from bone marrow mononuclear cells. The genomic TP53 gene was amplified by polymerase chain reaction, and the amplified DNAs were directly sequenced. Results Direct DNA sequence showed that the Pro/Pro homozygote was observed in six patients (18%), Pro/Arg heterozygote in 12 (35%) and Arg/Arg homozygote in 16 (47%). There was no significant difference in the frequency of the polymorphism between the 34 Japanese MM patients and the healthy Japanese individuals (P=0.44). Thus, association of codon 72 polymorphism with myeloma risk has failed to be elucidated. The response rate to thalidomide therapy was 33% in the patients with Pro/Pro, 27% in Pro/Arg and 44% in Arg/Arg (P=0.49), respectively. Other clinical backgrounds including age, sex, Durie-Salomon stage, ISS stage, serum creatinine, albumin, b2M, calcium, hemoglobin levels and M-protein type were not correlated with TP53 codon 72 polymorphism, either. Progression free survival (PFS), overall survival (OS) and post-relapse survival were shown in Figure 1. The patients with Pro allele tended to show shorter PFS; 5 weeks for the patients with Pro/Pro versus 32 weeks for those with Pro/Arg plus Arg/Arg (P=0.07) (Figure 1). Overall survival (OS) of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 18 weeks, 49 weeks and 133 weeks, respectively (P=0.027). Especially, the patients with Pro/Pro allele revealed significantly shorter OS compared with those with Pro/Arg plus Arg/Arg (18 weeks versus 100 weeks, P=0.023) (Figure 1). Significant difference of OS in patients with Pro/Pro+Pro/Arg vs Arg/Arg (P= 0.032) suggested the dominant effect of Pro allele for poorer prognosis. Post-relapse survival of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 11, 42 and 64 weeks, respectively (P=0.054). Post-relapse survival for Pro/Pro versus Pro/Arg plus Arg/Arg were 11 weeks versus 64 weeks (P=0.029). Conclusion These results indicated that codon 72 polymorphism did not correlated with myeloma risk, but significantly associated with therapeutic outcome. Namely, the patients with Pro allele revealed earlier relapse and shorter post-relapse survival, resulted in shorter OS in thalidomide therapy. Further evaluation is needed to clarify whether the codon 72 polymorphism will be a new prognostic marker for the treatment with novel drugs. Disclosures: No relevant conflicts of interest to declare.

Multiple Myeloma Profile In Latin America: Clinical and Epidemiological Observational Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5327-5327
Author(s):  
Vania T M Hungria ◽  
Angelo Maiolino ◽  
Gracia Aparecida Martinez ◽  
Carmino A De Souza ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Clinical Features ◽  
Median Overall Survival ◽  
High Dose Chemotherapy ◽  
Patterns Of Care ◽  
Disease Stage ◽  
High Dose

Abstract Introduction Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries. Objective To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America. Patients and Methods This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012). Results Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p<0.001). The multivariate prognostic model included patient baseline variables that were associated with mortality in the Kaplan-Meier univariate analyses. Only hypercalcemia, DSS II and III, ISS stage III andnon- high-dose chemotherapy were independent predictors of mortality. Conclusion This current study, which is the largest case series of MM patients in Latin America, recognizes the feasibility of large, collaborative, observational studies among various tertiary-care hematology centers in Latin America. Note We will present more details related to the demographic and most frequently used treatments in Latin America for newly diagnosed and relapsed patients in these LA countries. Disclosures: No relevant conflicts of interest to declare.

Addition of Bortezomib (Velcade™) to High Dose Melphalan (Vel-Mel) as an Effective Conditioning Regimen with Autologous Stem Cell Support in Multiple Myeloma (MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 929-929 ◽  
Author(s):  
Klaus Hollmig ◽  
Julie Stover ◽  
Giampalamo Talamo ◽  
Maurizio Zangari ◽  
Raymond Thertulien ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Conditioning Regimen ◽  
High Risk Population ◽  
High Dose ◽  
Complete Disappearance ◽  
Care Hospital ◽  
Platelet Recovery

Abstract Velcade has shown promising activity alone and, more recently, in combination with other anti-myeloma agents (dexamethasone, thalidomide, doxil, standard dose melphalan) for relapsed or refractory multiple myeloma. We have now explored the efficacy and safety of Velcade™ 1.0 or 1.3mg/m2 administered on days -4 and -1 prior to Melphalan, which was given in two fractionated doses for a total of 100–250 mg/m2 on days -4 and -1 or as single dosing on day -1 supported on day 0 by PBSC infusion. Follow-up is now 1–5 months; detailed follow-up data will be available at presentation. Of 37 patients currently evaluable for toxicity, 27 are also evaluable for response. Patient characteristics are outlined in Table 1, depicting a high risk population. The treatment was administered in the out-patient setting in 37 patients, 27 of whom were entirely managed through ambulatory care. Hospital admission was required for pneumonia in 4, sepsis in 3, nausea and vomiting in 2 and ileus in 1 patient. In 37 evaluable patients, hematopoetic recovery depended upon the timing of PBSC collection (prior to the first, second or the Vel-Mel transplant). Neutrophil recovery to > 1,000/μL occurred at a median of 13 days and platelet recovery to 50,000/μl at a median of 17 days. Non-hematologic toxicities included ≥ grade III mucositis in 5, diarrhea in 11, febrile neutropenia in 5, pneumonia/sepsis in 14, and fatigue in 22 patients. No fatal complications were seen. Of 27 evaluable patients, partial response (≥ 75% of serum M protein reduction, ≥ 75% of urinary M excretion) was obtained in 9 (39%) including 6 (26%) who showed a complete disappearance of serum M and urine M. Bone marrow follow-up examinations were available in 17 patients and revealed a median reduction in plasmacytosis of 75% including 2 patients achieving a normal bone marrow plasmocytosis Our results are promising and demonstrate that Vel can be safely added to Mel at doses as high as 250 mg/m2 in fractionated dosing with a high response rate also in high-risk, advanced disease. This approach will be formally evaluated in a randomized trial comparing tandem transplants with Mel 200 mg/m2 alone versus added Vel 1.0 mg/m2 on days 1 and 4 followed on each day by Mel 140 (total 280 mg/m2). Velcade 1.0 mg/m² Velcade 1.3 mg/m² Parameter Mel 250 Mel 220–240 Mel 200 Mel 100–150 Mel 250 Mel 200 Mel 100–150 N 4 4 12 10 4 2 1 % AGE ≥ 65 0 25 33 30 0 0 100 %Abn Cytogen 75 0 8 30 50 50 0 % Prior Autotx 75 25 33 40 75 0 100 % Prior VTD 50 25 25 30 75 50 100

Achievement of CR and nCR Before and After First High-Dose Therapy Followed by Autologous Stem Cell Transplantation Is a Major Marker for Long-Term Survival in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3400-3400
Author(s):  
Hartmut Goldschmidt ◽  
Gerlinde Egerer ◽  
Ute Hegenbart ◽  
Markus Munder ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Significant Prognostic Factor ◽  
High Dose Therapy ◽  
Free Survival ◽  
Before And After ◽  
Duration Of Response

Abstract Abstract 3400 Poster Board III-288 To analyse the impact of complete response (CR), near CR (nCR) and very good partial response (VGPR) before and after first high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) on overall survival (OS) and progression-free survival (PFS), we evaluated all patients with multiple myeloma (MM) who underwent an ASCT in frontline treatment at our centre. The transplantations were performed between June 1992 and February 2009 giving a minimum follow up of 5 months after ASCT. The retrospective analysis included a total of 994 patients (579 males and 415 females) with a median age of 58 years at time of first ASCT (range 25 - 76 years). Median follow-up after first ASCT was 5.8 years. All patients suffered from symptomatic MM. Before induction treatment 48%, 31% and 21% of patients were in ISS-stage I, II and III, respectively. The following induction regimes were applied prior to HDT: VAD (n=683), TAD (n=74), PAD (n=64), and other regimes (n= 173). The patients were treated with HDT once (n= 460), twice (n=437) or thrice (n=97). 91 patients received an allogeneic SCT, 30 of these before first progression after ASCT. These were censored for PFS at time of allogeneic SCT. Maintenance therapy (interferon n=332, thalidomide n=203, bortezomib n=48 or others n=13) was administered in 596 patients. Overall survival and progression-free survival were calculated from the time of first ASCT. The median OS time was 5.7 years and the median PFS was 2.2 years. Log-rank test, univariate and multivariate Cox PH regression as well as landmark analyses were utilized to assess the prognostic impact of response. We analysed the effect of achievement of CR, of nCR or CR and of VGPR or CR or nCR before and after HDT, respectively. Achieving CR or nCR is a highly significant prognostic factor for PFS and OS before (p<0.001 and p=0.01, respectively) and after first HDT (both p<0.001). The group including VGPR showed superior outcome when assessed after HDT, driven by the effect of CR/nCR. When adjusting for the effect of age, beta-2 microglobulin before ASCT, albumin before ASCT, new drugs before ASCT (thalidomide and bortezomib; yes/no), second ASCT within 9 months (yes/no), maintenance therapy (yes/no), and date of first ASCT, achieving CR or nCR remained a significant prognostic factor (PFS after ASCT: HR=0.66 [0.54;0.80], p<0.001; OS after ASCT: HR=0.65 [0.51;0.83], p=0.001). In addition, we analyzed the effect of duration of response compared to response achievement per se. Patients who sustained their remission (overall response = PR and better) at 3 yrs after first ASCT had a favourable prognosis with respect to OS compared to patients losing remission. Conclusion: In our single-center cohort achieving CR or nCR before and after first HDT is highly prognostic for PFS and OS in MM. Sustained duration of response is also associated with an improved prognosis (3 years landmark analysis). At our centre we recommend that patients not achieving at least an nCR should be treated with a second cycle of HDT. Disclosures: No relevant conflicts of interest to declare.

Intensified Chemotherapy Regimen for Very High Risk Childhood B-Precursor Acute Lymphoblastic Leukemia (B-ALL): Results From Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05–01

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3563-3563
Author(s):  
Lynda M. Vrooman ◽  
Kristen E. Stevenson ◽  
Marian Harris ◽  
Donna S. Neuberg ◽  
Stephen E. Sallan ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Total Duration ◽  
Pcr Analysis ◽  
High Dose ◽  
Induction Phase ◽  
Cell Transplant ◽  
Very High

Abstract Abstract 3563 Background: High levels of minimal residual disease (MRD) at the end of 4-weeks of multiagent induction chemotherapy have been shown to be associated with a high risk of subsequent relapse in pediatric patients (pts) with B-ALL. Published reports indicated that pediatric B-ALL pts with high end-induction MRD had event-free survival (EFS) rates < 50% when treated with standard chemotherapy.[Zhou, Blood 2007; Borowitz Blood 2008] Pts with high-risk (HR) cytogenetic abnormalities, such as low hypodiploidy and MLL gene rearrangements (MLL-R) also have a high relapse risk. On DFCI ALL Consortium Protocol 05–01, we piloted an intensified regimen for B-ALL pts with high end-induction MRD and/or HR cytogenetics. Methods: Between 2005–2010, 482 evaluable pts aged 1–18 years with B-ALL were enrolled. Pts were initially classified as standard-risk (SR) or high-risk (HR) based on NCI age/WBC criteria. MRD was prospectively evaluated at the end of the 4-week induction phase via RQ-PCR analysis of IgH or TCR rearrangements. Results were reported as the ratio of copy numbers of target gene:GAPDH; a ratio >0.001 was considered high MRD. Pts with high MRD or HR cytogenetics (hypodiploidy with <45 chromosomes or MLL-R) were reclassified at the end of induction phase as very high risk (VHR), and received 2 additional chemotherapy cycles beginning at week 7 (cycle 1: cyclophosphamide, low-dose cytarabine, 6-MP; cycle 2: high-dose cytarabine, etoposide, dexamethasone, L-asparaginase), followed by the DFCI ALL Consortium HR consolidation phase, including 30 weeks of L-asparaginase and doxorubicin to a cumulative dose of 300 mg/m2. After consolidation, pts received a standard maintenance phase. Total duration of treatment was 25 months. Results: 51 pts (11%) were classified as VHR, 25 of whom had been initially classified as SR and 26 as HR. 35 VHR pts had high end-induction MRD as the sole VHR criterion; 16 had HR cytogenetics. 9 pts relapsed (all marrow-involved) and 1 pt developed a secondary AML. There were no deaths in first remission. With median follow-up of 4.4 yrs, the 5-yr EFS (95% confidence interval) for all 51 VHR pts was 76% (60,87)[Figure 1] and 5-yr overall survival was 81% (60,92). The 5-yr EFS was 81% (59,90) for the 35 pts with high MRD. Conclusion: Intensification of chemotherapy (without stem cell transplant) resulted in a relatively favorable EFS in VHR B-ALL pts (defined by the presence of either high end-induction MRD or HR cytogenetics). More pts and longer follow-up will be necessary to confirm these promising results. Disclosures: No relevant conflicts of interest to declare.

Would Be Cyclophosphamide, Thalidomide and Dexamethasone (CTD) a Possible Treatment For Multiple Myeloma Where Is Not Possible New Drugs?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5385-5385
Author(s):  
Marcelo Bellesso ◽  
Marcela Cavalcante de Andrade Silva ◽  
Rodrigo Dolphini Velasques ◽  
Helena Visnadi ◽  
Roberta Shcolnik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
New Drugs ◽  
Stage Iii ◽  
High Dose ◽  
Primary Therapy ◽  
First Line ◽  
In The Beginning

Abstract Background Nowadays, the best evidence for symptomatic patients with Multiple Myeloma (MM) is initial induction therapy with more than two drugs that contains bortezomib. If patients are eligible it is established the use of high dose chemotherapy and autologous stem cell transplantation (ASCT). We do not have to prescribe in Brazilian public health service, due to economic reasons, new drugs such as: bortezomib and lenalidomide. On the other hand, it is known that Cyclophosphamide, thalidomide and dexamethasone (CTD) regimen is an effective primary therapy for MM and it is widely used in some countries such as United Kingdom. We have been prescribing for first line therapy CTD regimen in our clinical practice for approximately 4 years. Thus, we performed a retrospective analysis of patients with MM treated with CTD regimen in the Instituto do Câncer do Estado de São Paulo. Here we present response rate, reduction dose rate, toxicity rate and progression free survival (PFS) and overall survival (OS). Patients and Method We studied 71 patients that were submitted as first line treatment CTD, during 2006-2012. This regimen consists: Cyclophosphamide 500mg orally on days 1, 8, 15; Thalidomide 100mg orally on days 1 to 28 and Dexamethasone 40mg orally on days 1 to 5 and 14 to 18, every 30 days. To sensitive and eligible patients, we have submitted them for  ASCT. PFS and OS were calculated by the Kaplan-Meier method. PFS was calculated from the start of treatment until progression or death or last follow-up and OS until death or last follow-up. GraphPad Prism (v5.0) software was used for statistical calculations, and P values < 0.05 were considered to be statistically significant. Results In the 71 patients, 54.2% were male patients, the median age was 57.81 years old (± 7.96). Out of the 71 patients (78.7%), were classified by Durie Salmon staging as IIIA or IIIB and 30% presented stage III for the International Staging System (ISS). Fifty seven (80.2%) were considered eligible for ASCT in the beginning of treatment. Moreover, the evidences of end-organ damage felt related to the plasma cell disorder were: lytic lesions 78.6%; anemia 51.4%, renal failure 20% and hypercalcemia 11.4%. The median of CTD cycles prescribed was 6.44 (± 2.62) and 47.1% were treated in the beginning without adjustment doses. It was evidenced 5.63% deaths related to the treatment. It was observed adjustment doses after 1st cycle in 35.7% of patients due to: peripheral neuropathy 36%, tremor 16%, thrombosis 12%, bradycardia 12% and others 24%. It was observed in 71 patients: 6 (8.45%) stable disease (SD); 4 (5.63%) progressive disease (PD); 26 (36.66%) partial response (PR); 15 (21.1%) very good partial response (VGPR) and 16 (22.53%) complete response (CR), it was not possible to analyze 4 (5.63%) patients due to death. Of total eligible patients to ASCT, 57.62% were submitted for ASCT and in this moment 6.7% have been preparing for ASCT. The median of PFS was 29.2 months (CI 95% 0,22-0,66) and  median of OS was not achieved. It was observed difference in OS between patients with stage III for the ISS: 28,92 months versus (vs) patients with stage I and II median not reached, p = 0.0105. PFS study demonstrated curves that patients responding to CTD at least VGPR (VGPR+CR) presented better median PFS 37.48 months than others patients (PR+PD+SD) 17.93 months, p=0.0018.  Only patients that presented PD and SD response to CTD had a significantly shorter OS median 19.21 months than patients responses at least PR (PR+VGPR+RC) median was not reached, p < 0.0001. Conclusion We conclude that CTD is a feasible regimen where is not possible to prescribe new drugs, with acceptable toxicity. Moreover, patients that presented at least VGPR and at least PR to CTD demonstrated better PFS and OS, respectively. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long Term Survival Analysis of Multiple Myeloma Patients Receiving Induction Therapy+ Autologous STEM CELL Trasplantation, Comparing Velcade-Dexametasone to Alkylating Polichemotherapy As Induction Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5764-5764
Author(s):  
Sara Caceres ◽  
Rocio Cardesa ◽  
Carmen Cabrera ◽  
M. Helena Bañas ◽  
Fatima Ibañez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Autologous Bone Marrow Transplantation ◽  
Young Patients ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
Term Survival ◽  
The Impact

Abstract Introduction: Multiple Myeloma (MM) is an incurable disease. In young patients, autologous bone marrow transplantation (ABMT) remains a cornerstone treatment after induction therapy. Induction therapy has varied during time, from alkylating polychemotherapy (VBAD,VCMP) or VAD chemotherapy (AVAD) to Velcade-Dexametasone based regimens (VD). We present results of follow-up of a large cohort of patients treated with ABMT. We described overall survival (OS; from transplant to death by any cause) and progression free survival (PFS; from transplant to death by any case or progressive disease defined by reappearance by inmunofixation, or duplication of monoclonal peak after ABMT) , and the impact of induction therapy regiments. Patients: 183 patients transplanted from 2002 to 2017. The median age of the patients was 59 years (33-72). Before 2008 all the patients were treated in alkylating based chemotherapy (42 patients). After 2008 patients were treated with VD based regimens (141patients). Only 12 patients received maintenance therapy based in PETHEMA trials 2005 and 2012. No one patient received a planed second transplant; only 32 patients received a second transplant after relapse as consolidation therapy. Results: Median follow-up of patients still alive is 3.65 years (0.15-14.77). Median OS of all patients was 9.12 years (95% confidence interval (CI): 6.28-NR); Median PFS was 3.02 years(95% CI: 2.46-3.76). At 13 years only 2% of patients remains progression free (CI: 0.00-17%). There were significant differences between patients treated before and after VD regimens. The median OS of patients treated with APVAD was significantly shorter compared to VD (6.22 years, CI[3.39-12] vs. NR, CI[6.28-NR], p=0.025) (HR=0.49, p=0.01). Conclusions: VD schemes of induction before ABMT have improved remarkably OS inpatients with Myeloma; nonetheless, plateau is not observed in EFS. Further analysis must address if EFS could represent a strong indicator of OS, mainly due to novel effective salvage therapies after relapse/refractoriness could be a confounding factor. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document