Clinical Experience Of Lenalidomide Plus Low Dose Dexamethasone As First-Line Therapy For Multiple Myeloma At a Large County Hospital Caring For An Indigent Population

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5399-5399
Author(s):  
Yehuda E. Deutsch ◽  
Daniel J Dammrich ◽  
Jesus C Fabregas ◽  
Agustin Pimentel ◽  
Alexandra Stefanovic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Real World ◽  
Patient Population ◽  
County Hospital ◽  
Published Data ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background There is ample data for the response rates and clinical outcomes for patients with newly diagnosed multiple myeloma (MM) treated with first-line lenalidomide and dexamethasone (LEN/DEX). Phase II and III studies have reported objective response rates (ORR) in the range of 70-90%.  However, extrapolating from clinical trials to ‘real world' clinical practice is sometimes difficult. This is particularly so when it comes to large city hospital systems such as Jackson Memorial Hospital (JMH) in Miami, Florida. JMH is the third-largest public hospital and third-largest teaching hospital in the United States. Patients are primarily uninsured or insured through Medicaid. Additionally, one might surmise, that for a medication like LEN- with a relatively narrow therapeutic index, high cost, and cumbersome prescribing/dispensing requirements- outcomes in the ‘real world' might be inferior to those cited in clinical study. We endeavored to explore such outcomes in JMH to determine whether the benefits of this high cost drug in this setting are concordant with published data. Methods We conducted a retrospective analysis of all patients enrolled into the Celgene patient assistance program and prescribed LEN from January 1, 2010 through July 30, 2013 at JMH. We identified 96 patients enrolled into this program, 35 patients received LEN/DEX as first-line therapy for MM and are evaluable for this analysis. The primary end-point for analysis was response at 4 months. Results Medical records of 35 patients were reviewed. The mean age was 59 (46-75), majority of patients were female (60%), and 29% were black. Consistent with our patient population, 71.4% of patients were Hispanic, 44% were uninsured, and 64% had Medicaid. IgG (60%) was the most common heavy chain involved while 3 patients had light chain disease only. The majority of patients (88.6%) had stage III disease by the Durie-Salmon criteria, and 37.1% had ISS stage III disease. Cytogenetic studies were evaluable in 30 patients: 66.7% were standard-risk, 30% intermediate-risk and 3.3 % high-risk according to mSMART risk classification. At 4-month follow-up, 26 (74.3%) patients had an OR: 6 (17.1%) patients had CR, 7 (20%) had VGPR, and 13 (37.1%) had PR. 6 (17.1%) patients had progressive disease, change in therapy, or were lost to follow-up. There were no documented deep venous thromboses, a known risk of LEN therapy. Only 8 patients (23%) underwent autologous stem cell transplant following primary therapy. Conclusion Responses with upfront LEN/DEX in MM at JMH, were relatively similar to published data in large clinical studies. This provides support for the extrapolation of data from well supported clinical trials at fully-resourced medical institutions, for an oral chemotherapy drug with significant potential toxicities and logistical barriers, to a primarily Medicaid patient population in a county hospital. Disclosures: No relevant conflicts of interest to declare.

Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 825-825
Author(s):  
Dmitriy Zamarin ◽  
Manisha Bhutani ◽  
Danielle Chimento ◽  
Sergio Giralt ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Soft Tissue ◽  
First Line ◽  
Post Transplant ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group A ◽  
One Year ◽  
Group B

Abstract Abstract 825 BACKGROUND: Autologous stem cell transplantation (ASCT) is a widely used therapeutic option in first line treatment of multiple myeloma (MM). However, many patients eventually relapse. While precise knowledge of relapse and progression (R/PD) patterns would be important to generate evidence based surveillance recommendations after ASCT, such data is limited in the literature, especially in the era following the introduction of the free light chain assay. The purpose of this study is to examine the patterns of post-ASCT relapse and to derive evidence based recommendations for optimal surveillance of patients. METHODS: We performed a retrospective analysis on 258 patients with MM who underwent ASCT within one year of diagnosis at MSKCC between 2000 and 2010, as part of first line therapy. We used the IMWG standard criteria for serologic and clinical R/PD. We first determined for all patients the date of serologic R/PD. Patients identified as having serologic R/PD were further examined to determine whether clinical (anemia, renal failure, hypercalcemia, development of soft tissue lesions), radiologic (skeletal survey) or urinary R/PD had anteceded serologic R/PD. Several groups of patients were derived and further analyzed in terms of relapse patterns and adequacy of follow up. RESULTS: Among 258 patients, 173 were determined to have serologic R/PD at a median of 19.2 months post-transplant. Among these patients, on the dates of their serologic R/PD, 17 (9.8%) had concurrent overt symptomatic evidence of clinical/radiologic R/PD (Group A symptomatic R/PD), while 156 (90.2%) were found to have isolated asymptomatic serologic R/PD without apparent evidence of concomitant clinical/radiologic R/PD (Group B asymptomatic R/PD). Group A included patients with distinct and sometimes coinciding clinical characteristics (poor risk cytogenetics with aggressive disease (n=3), leptomeningeal relapse (n=1), soft tissue relapse (n=4) and acute severe anemia at relapse (n=3)); patients with IgA gammopathy (n=5); and patients considered to have inadequate serologic follow up intervals (range of follow up interval between date of serologic R/PD and prior serologic testing 149 to 245 days) (n=6). Upon further examination of group B, 44 patients had radiologic imaging at the time of serologic R/PD (within 4 weeks following the date of serologic R/PD). Fourteen among them (32%) had evidence of new bone lesions. Among all 173 patients with serologic R/PD, 83 patients had a skeletal survey within one year prior to the date of serologic R/PD. Only 3 (3.6%) had evidence of radiologic R/PD anteceding serologic R/PD. All 3 patients were considered to have had inadequate serologic follow up interval (Range 208 to 252 days). Abnormal urine immunofixation (UIF) anteceded serologic R/PD in 5 out of 41 (12%) patients tested who had achieved CR post transplant. In these patients the abnormal UIF anteceded the serologic R/PD by a mean of 2.4 months. Abnormal UPEP anteceded serologic R/PD by 1.9 months in only 1 out of 40 (2.5%) patients tested who had achieved less than CR post transplant. CONCLUSIONS: Based on the results of this analysis, several conclusions can be drawn: 1) The vast majority of R/PD in patients with MM are asymptomatic R/PD detected first by serologic studies. A small percentage of patients (those with aggressive cytogenetics, specific relapse types including soft tissue, severe cytopenia, and IgA gammopathy) will have symptomatic R/PD with overt concomitant evidence of clinical and/or radiologic R/PD at the time of serologic R/PD; 2) Among patients who have apparent asymptomatic R/PD, a significant percentage will have evidence of skeletal lesions and therefore imaging should be recommended in these patients; 3) In the absence of serological R/PD, routine surveillance screening with yearly skeletal surveys cannot be recommended based on this analysis since this test was not useful in any of the analyzable patients in whom it was obtained; 4) Aside from few patients in CR whose relapse may be detected earlier by UIF (with probably no clinical benefit), all patients with multiple myeloma whose disease progresses will have serologic R/PD at the time of progression and follow up limited to serologic testing may well be sufficient for monitoring patients with MM post transplant. Disclosures: No relevant conflicts of interest to declare.

Late Relapse in Hodgkin Lymphoma (HL): A Retrospective Analysis of Patients Enrolled on Clinical Trials at the Istituto Nazionale Tumori of Milan (INT-MI)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2697-2697 ◽  
Author(s):  
Simonetta Viviani ◽  
Alberto Mussetti ◽  
Oreste Di Bartolo ◽  
Antonello Cabras ◽  
Pinuccia Valagussa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Retrospective Analysis ◽  
Salvage Therapy ◽  
Prognostic Score ◽  
Late Relapse ◽  
First Line ◽  
First Line Therapy ◽  
Conventional Dose ◽  
Line Therapy

Abstract Background The majority of relapses in HL occur within the first three years from end of first-line treatment. Late relapses, occurring after more than five years, are rare events and there is no consensus on the optimal treatment. Aims of study The aim of our retrospective analysis was to assess the proportion of relapses occuring > 5 years in patients enrolled on clinical trials at INT-MI between 1974 and 2007, to evaluate prognostic factors, treatment outcome and survival. Patients and Methods From 1974 to 2007, 1089 consecutive HL patients, previously untreated with chemotherapy (CT), were enrolled on clinical trials at the INT-MI; 959 patients in complete remission (CR) after first-line CT or combined modality treatment were included in this study. In all patients who relapsed >5 years from end of frontline treatment a second biopsy was performed to prove HL histology at relapse. Failure-free survival (FFS) was calculated from the date of late relapse until documented relapse from CR after salvage therapy, disease progression during or within 3 months from end of salvage therapy, or death, whichever came first. Overall survival (OS) was calculated from the date of late relapse to last follow-up visit or death. Results A total of 31 complete responders after first-line therapy relapsed after > 5 years. Median time from end of first-line therapy to relapse was 115 months (range, 63-299). Main patient characteristics at late relapse were as follows: males: 71%; median age: 48 years (range, 20-67); classical histology: 81%; stage III/IV: 55%; B Symptoms: 48%; extranodal disease: 26%; > 3 involved sites: 52%; bulky disease: 13%; GHSG prognostic score ³ 1: 52%; MSKCC prognostic score ³ 1: 61%. Conventional dose salvage chemotherapy (CT) was delivered to 64.5% of patients: 9 patients were retreated with the same regimen employed as front-line therapy (MOPP alternated with ABVD), 5 were retreated with ABVD alone, 6 received non cross-resistant regimens. High-dose chemotherapy (HDCT) with hematopoietic stem cell reinfusion (ASCT) was delivered to 35.5% of patients. With a median follow-up of 9 years, 10-year FFS was 57% (95% Confidence Interval CI: 33-75) and OS was 64% (95% CI: 41-80). In univariate analysis only age > 48 years was associated with an inferior FFS [44 % (95% CI:18-68) vs 92% (95% CI:54-99), p=<0.001] and OS [40% (95%CI:16-65) vs 100% , p=0.03]. There was no significant difference in the outcome of patients treated with HDCT+ASCT compared to those treated with conventional dose CT [FFS 75% (95%CI: 30-93) vs 63% (95%CI: 36-82), p=0.78; OS 71% (95%CI: 26-92) vs 64% (95%CI: 34-83),p=0.21]. Conclusions: This retrospective cohort of patients with late relapse HL is to date one of the largest case series and with the longest follow up. Besides the rarity of these cases, late relapse of HL appears to have a good prognosis. Classical prognostic scores for relapsed HL have no role in this setting. In the subgroup analyses, being older than 48 years conveys a worse prognosis. HDCT and ASCT does not appear to confer an important survival advantage over conventional dose CT. Figure 1. Figure 1. Disclosures Viviani: Takeda Italia SpA: Consultancy; Teva Italia SpA: Consultancy; Italfarmaco SpA: Consultancy; Takeda International: Consultancy. Corradini:Celgene: Consultancy; Novartis: Consultancy.

scholarly journals Real-World Treatment Patterns and Outcomes Among Patients with Hairy Cell Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2125-2125
Author(s):  
Sudeep Karve ◽  
Victoria Divino ◽  
Andrew Gaughan ◽  
Mitch DeKoven ◽  
Guozhi Gao ◽  
...  
Keyword(s):  
Health Plan ◽  
Real World ◽  
Index Date ◽  
Treatment Patterns ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background and Objective : Hairy cell leukemia (HCL) is a rare condition and accounts for ~2% of all leukemia cases in the US. NCCN guidelines recommend first-line agents including pentostatin and cladribine among patients with HCL. However, a paucity of data exists with regard to real-world treatment patterns among patients with HCL. Current study evaluates treatment patterns and associated clinical outcomes among patients with HCL using a large US administrative claims database. Methods : This retrospective observational study was conducted using the IMS Health PharMetrics Plus Health Plan Claims Database (2006-2014), which includes over 150 million unique health plan members across the US and is nationally representative of the commercially-insured US population. Data includes date stamped medical and pharmacy records along with information on health plan enrollment. Individuals with at least 2 medical claims with a diagnosis for HCL (identified using ICD-9-CM cod: 202.4x) were selected and the first observed claim defined the "index date." Patients <18 years of age at index date or with other malignancies during 6 months (the "pre-index period") prior to index date were excluded. Patients were required at least 90 days of continuous enrollment (the variable "follow-up period") in the health plan post index date with exception of patients who died within 3 months of diagnosis. Patients were followed until death (recorded on inpatient discharge disposition), end of enrollment or end of database, whichever occurred earlier. Study measures including patient demographic and baseline clinical characteristics, line of therapy (LOT), treatment patterns, relapse (receipt of same or new regimen in subsequent LOT following a gap of 365 days) and refractory disease (receipt of same or new regimen where the gap of two adjacent LOTs was <365 days) and post-treatment complications were assessed during the follow-up period. All analyses were descriptive in nature. Results : The study cohort included 749 patients after applying the selection criteria (mean follow-up from diagnosis 32 months). At diagnosis, the mean age (standard deviation) of the study cohort was 56 (10) years and majority of patients were male (77%). Mean baseline comorbidity burden (assessed using Charlson Comorbidity Index score) was 0.8 (1.1) with hypertension (24%) and aplastic anemia (22%) being the two most common co-morbidities. Only 38% (n=282) of patients received first-line chemotherapy post diagnosis. Majority initiated first-line cladribine (76%) as a single agent, while 9% had evidence of single agent pentostatin. Mean time to initiation of first-line therapy from diagnosis was 132 (294) days and average time on first-line therapy was 34 (104) days. Among patients with first-line therapy 14% received second-line therapy and rituximab (53%) and cladribine (21%) were frequently observed second-line agents. Post first-line therapy, mean time to initiation of second-line therapy was 303 (406) days. Among second-line initiators, 76% had refractory disease and 24% had relapsed following first-line. Neutropenia and fever were frequently reported complications while on chemotherapy. Conclusion : The real-world chemotherapy utilization patterns observed in this study are consistent with the NCCN guidelines with cladribine and pentostatin being the agents of choice for first-line therapy. Following diagnosis, more than one-third of patients initiated chemotherapy and only a small proportion of these received second-line chemotherapy suggesting durable response with first-line therapy. Limited follow-up post first-line therapy may have impacted the proportion of patients initiating second-line therapy as well as categorization of refractory and relapse disease. Disclosures Karve: AstraZeneca: Employment. Divino:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gaughan:AstraZeneca: Employment. DeKoven:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gao:MedImmune: Employment. Lanasa:MedImmune: Employment.

scholarly journals Aspirin Use and Survival in Multiple Myeloma Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3250-3250 ◽  
Author(s):  
Catherine R. Marinac ◽  
Graham A Colditz ◽  
Bernard Rosner ◽  
Irene M. Ghobrial ◽  
Brenda M Birmann
Keyword(s):  
Multiple Myeloma ◽  
Clinical Data ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
First Line ◽  
Use Patterns ◽  
First Line Therapy ◽  
Line Therapy ◽  
Overall Mortality

Abstract Background: Multiple myeloma (MM) is a lethal malignancy with 5- and 10-year survival rates of 46.7% and 20.6%, respectively. Marked advancements in treatment have improved survival within the last decade but are expensive and do not achieve cure. It is known that inflammation is important in MM pathogenesis, and regular aspirin use has been shown to confer a reduced risk of incident MM. However, the influence of aspirin on survival after diagnosis of MM is unknown. We investigated this question prospectively in two large cohorts. Methods: We identified 567 men and women diagnosed with MM between 1980 and 2012 in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). Participants in both cohorts reported aspirin intake biennially on follow-up questionnaires beginning in 1986 in HPFS and 1980 in NHS. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for MM-specific and overall mortality through 2015 according to aspirin use patterns. We also examined differences in MM clinical characteristics by aspirin use patterns in a subset of participants with available clinical data. Results: After a median follow-up of 40 months, there were 135 total deaths (76%) and 107 MM−specific deaths (60%) among 177 participants who used aspirin after MM diagnosis, compared with 222 total deaths (90%) and 195 MM−specific deaths (79%) among 247 participants who did not use aspirin. Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for MM−specific mortality of 0.55 (95% confidence interval [CI], 0.41, 0.73) and for overall mortality of 0.58 (95% CI, 0.45, 0.75), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, pre-diagnosis aspirin use, and number of comorbidities. We also observed evidence of a dose response association between postdiagnosis aspirin quantity for both MM-specific and overall mortality (P-trend <0.01). The association between postdiagnosis aspirin use and MM-specific and overall mortality were not materially different in models that excluded deaths that occurred within 12 months of completing the postdiagnosis aspirin assessment. We could not adjust for first line therapy, but adjustment for year of diagnosis may partially control for first line therapy in these cohorts. In a subsample (n=225) of participants with clinical data available, we did not observe statistically significant differences in the clinically presenting features of MM by post diagnosis aspirin use. We also did not observe statistically significant associations between pre-diagnosis quantity or duration of aspirin use and MM-specific or overall mortality. Conclusions: Although lack of adjustment for clinical parameters is a limitation, the findings suggest that aspirin use after MM diagnosis is associated with a lower risk of MM−specific and overall mortality. Disclosures Ghobrial: Celgene: Consultancy; BMS: Consultancy; Janssen: Consultancy; Takeda: Consultancy.

Progression of Follicular Lymphoma within 24 Months of First Treatment (POD -24) As a Predictor of Overall Survival - a Single Center Retrospective Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1534-1534
Author(s):  
Guy Bitansky ◽  
Elena Vasilev ◽  
Maya Zlotnick ◽  
Elena Ribakovsky ◽  
Ohad Benjamini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Real World ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Early Progression ◽  
Progression Of Disease ◽  
Routine Imaging

Background: Follicular lymphoma (FL) is the most common indolent lymphoma in the western world with a median survival approaching 20 years. However, the course of the disease is extremely heterogeneous and therefore, at diagnosis it is difficult to predict survival. Roughly 20% of patients experience rapid progression of disease post first line treatment. Progression of disease within 24 months of first treatment (POD24) was previously identified a robust predictor of reduced overall survival (OS) (Casulo et al., JCO, 2015). Aims: We aimed to validate POD24 as a predictor of poor OS in a real-world cohort of patients, which was not uniformly treated, including patients that were initially treated with radiation or observed at least 6 months prior to first line therapy. Methods: We thoroughly reviewed 635 patient's records that were diagnosed between 1987 and 2018. Patients with FL grade 3B or de-novo transformation, as well as those that were never treated, treated prior to the rituximab era or had missing relevant clinical data were excluded. POD24 was defined as time from first therapy (systemic or radiation therapy) to first documented progression (either clinical or by imaging). Overall Survival was defined as time from diagnosis to either last follow-up or death. Progression Free Survival (PFS) was defined as the time from first treatment to first documented progression, death or last follow-up. Survival was analyzed with Kaplan-Meier method and comparison of survivals was done with Log-Rank test. Multivariate analysis was conducted with Cox regression. Results: A total of 317 patients met the study inclusion criteria and were included in our analysis. Median age was 57 (23-87), 162 (51%) were male and 155(49%) female .Median follow-up was 7.5 years (0.24-24.4). FLIPI (available in n=149) was high in 41 (27%) patients, intermediate in 37 (25%) and low in 71 (48%). Eighty seven patients (27.4%) received radiation as their first treatment and 86 (27%) were initially observed. Systemic therapy regimens included alkylator based regimens (n=152, RCHOP-88), bendamustine based (45), fludarabine Based (32), and Rituximab alone (2). Maintenance therapy administration was documented in 119 patients. Progression was documented in 133 (42%) patients, and transformation in 34 (11%). Thirty four patients (11%) deceased. Median OS was not reached in our study cohort, and median PFS was 109 months (CI:68-150). Early progression (POD24) was captured in 68 (21.5%) patients. The OS of those patients was significantly lower than those whom did not progress within 24 months of first therapy (figure 1A, p&lt;0.0001). High FLIPI score also predicted lower OS (p=0.001). In multivariate analysis both factors remained significant (POD24 p=0.013, FLIPI p=0.023). In the group of patients that were initially observed (86), 18 had early progression after first treatment. In this group, OS did not differ between the patients that had POD24 vs those who did not (p=0.095). The same was true for patients that had radiation as their first line therapy (p=0.36). The impact of POD24 on OS was observed in patients that were treated with alkylator based regimens (p=0.02) as well as with bendamustine based regimens (p=0.028). In the Fludarabine treated patients no significant difference in OS was observed in the different POD24 groups, probably due to small sample size. Interestingly, POD24 did not predict inferior OS in 69 patients in whom progression was diagnosed by routine imaging (PET/CT or CT) (Figure 1B). However, it was borderline predictive (p=0.1) when progression was clinically diagnosed (n=38). Conclusions: Our real-world analysis validated the importance of POD24 as predictor of OS in patients who were treated at diagnosis with alkylator or bendamustine based regimens. POD24 did not predict survival in patients treated with radiation or in those initially observed, a result that may reflect their superior outcome. Notably, POD24 did not predict OS in patients that were diagnosed with progression by routine imaging. As we, and others use imaging studies frequently in the follow-up of FL patients, especially in first two years after therapy, the scenario of positive findings in imaging is relatively frequent. Our data suggest that random findings in imaging that do not have clinical expression may not predict inferior outcome which is of major clinical implications. Disclosures No relevant conflicts of interest to declare.

Deletion 17p in Unselected Newly Diagnosed Symptomatic Patients with Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5081-5081
Author(s):  
Efstathios Kastritis ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Elevated Serum ◽  
Initial Therapy ◽  
Novel Agents ◽  
Newly Diagnosed ◽  
First Line ◽  
Poor Outcome ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 5081 Multiple myeloma is characterized by significant genetic heterogeneity. Cytogenetic abnormalities are almost always present and specific cytogenetic features may be associated with poor outcome. Deletion of the short arm of the chromosome 17, involving the p53 locus, has been associated with poor outcome of the disease and the frequency of this abnormality increases in more advanced phases of the disease. Novel drugs may overcome, to a certain degree, the poor prognosis that is associated with certain cytogenetic abnormalities, but recent data indicate that neither bortezomib nor thalidomide or lenalidomide may overcome the deleterious effect of del17p either in newly diagnosed or in patients with relapsed disease. These data come from selected patients who have been treated within the context of clinical trials, most of which included intensified treatment such as single or double transplants. In order to assess the prognostic importance of del 17p in unselected patients with multiple myeloma, most of which received upfront novel agents, we analyzed 168 consecutive previously untreated patients, who were treated in a single center (Department of Clinical Therapeutics, University of Athens, Greece) who had available data on del17p, assessed by standard FISH methodology. Some of these patients were included in clinical trials, however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also included in the analysis, thus, being more representative of the general myeloma population. IMWG criteria were used for the assessment of response, progression-free (PFS) and overall survival (OS). Twenty-five (15%) of patients had del17p detected at initial diagnosis. The baseline clinical characteristics and conventional prognostic factors of patients with and without del17p were not significantly different. First line therapy was based on novel agents (thalidomide, bortezomib or lenalidomide) in 91% of patients and was similar for patients with or without del17p (p=0.887). Response to first line therapy was also similar (83% for those with del 17p versus 78% for those without, p=0.529). The quality of responses (CR, VGPR & PR) was also similar. Sixty percent of patients with a del17p and 39% of those without del17p have relapsed or progressed after initial therapy. The median progression free survival for patients with and without del17p was 18.5 versus 22.5 months respectively (p=0.065). In multivariate analysis, del17p was associated independently with shorter PFS (HR: 1.77, 95% CI: 1.021–3.07, p=0.042). Other factor that were independently associated with shorter PFS included age>65 years (p<0.001), ISS stage (p=0.028), low platelet counts (<130×109/L; p=0.032) and elevated serum LDH ≥300 IU/L (p<0.001). The median survival was significantly shorter for patients with del17p (29.5 versus 51 months, p=0.007). When we adjusted for other prognostic factors, including treatment with novel versus conventional agents, then the presence of del17 was independently associated with shorter survival (HR: 2.29, 95% CI: 1.15–4.6, p=0.019). Other factors associated with shorter survival included age >65 years (p=0.005), ISS-3 disease (p=0.038), low platelet counts (<130×109/L; p=0.005) and elevated serum LDH ≥300 IU/L (p=0.001). Importantly, median survival after first disease relapse for patients with del17p was 14 months while for patients without del17p was 42 months (p=0.01), despite the fact that in almost all patients novel agents were used as salvage treatment. In conclusion del17p remains an independent prognostic factor associated with poor survival in unselected patients with newly diagnosed MM, even when novel agents are used as initial therapy. Patients with del17p have very poor outcome after relapse, even with the use of novel agents as salvage therapy. Our data indicate that novel treatment and innovative strategies should be considered for these patients and that patients with del17p should be considered for participation in clinical trials of novel agents as soon as they relapse, since currently available treatment options offer limited benefit in these high risk patients. Disclosures: No relevant conflicts of interest to declare.

Updated Report of T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy for Upfront Use In Symptomatic Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3050-3050
Author(s):  
Tomer M Mark ◽  
Jennifer O'Loughlin ◽  
Morton Coleman ◽  
David Jayabalan ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Dexamethasone Therapy

Abstract Abstract 3050 Background: We hypothesized that the addition of thalidomide to BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) may improve the anti-myeloma activity of the combination while not adding to overall regimen toxicity, given the different side effect profiles of thalidomide and lenalidomide. We now report an update of the phase 2 trial of T-BiRD (thalidomide/Thalomid®, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) therapy for use in up-front treatment of symptomatic multiple myeloma (MM). Methods: Twenty-six patients with newly-diagnosed symptomatic MM were enrolled in a single-institution trial of T-BiRD. The T-BiRD regimen consists of clarithromycin 500mg twice daily, dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle, and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide is given at a dose of 50mg daily for the first week and thereafter at 100mg daily. All subjects had thromboprophylaxis with aspirin, 162 mg once weekly, 81mg on subsequent days throughout all treatment. Serum protein electrophoresis/immunofixation as well as free light chain determinations were done monthly. Bone marrow biopsy and skeletal imaging were done to confirm disease progression or complete response (CR). Results: Twenty-five patients had completed at least one cycle of T-BiRD and were evaluable. The median number of T-BiRD cycles was 5 (range 1–12). Response to T-BiRD, audited at time of autologous stem cell transplantation (ASCT) or other planned change in therapy, was: 1 (4%) progression of disease (PD), 4 (16%) stable disease (SD), 10 (40%) partial response (PR), 8 (32%) very good PR (VGPR), 1 (4%) complete response (CR), and 1 (4%) with unconfirmed CR, giving a overall response rate (ORR; 3PR) of 80% and a 3VGPR rate of 40%. Nine subjects subsequently underwent ASCT as part of a first line of therapy with T-BiRD induction. These subjects had an ORR of 100% to first-line therapy, with 2 maintaining PR (22%) 5 achieving VGPR (56%), and 2 achieving CR (22%). At three years of follow-up, median progression free survival (PFS) and event free survival (EFS) was not reached for first line therapy (median PFS and EFS censoring at time of ASCT were 65 and 53 weeks, respectively). Median overall survival (OS) was not reached; at 3-year follow-up, 2 patients had died of progressive myeloma, giving an overall survival rate of 92%. A total of 12 subjects (48%) experienced an adverse event (AE), 5 (20%) being study-drug related (RAE). Eight subjects (32%) withdrew from the study: 2 had grade 2 skin rash prior to initiation of full-dose thalidomide (RAE), 1 patient had grade 4 skin rash (Stevens-Johnsons syndrome, SJS) during cycle 1 (RAE), 1 had a TIA in cycle 2, 1 developed renal failure in cycle 1, 1 developed chest pain in cycle 3. Other toxicities include 1 patient with Grade 2 steroid myopathy (RAE), 1 patient with DVT of the leg (RAE), and 1 patient with atrial fibrillation. 2 subjects developed pneumonia (causitive organism not identified). 1 subject died of progressive myeloma prior to completion of 1 cycle. Conclusions: T-BiRD has promising activity as an induction regimen as part of first-line therapy for MM, with prolonged responses; however, toxicity limited extended use. T-BiRD does not appear to be superior to BiRD in ORR, likely due to shorter average time of regimen exposure (median 5 cycles of T-BiRD versus 13 cycles of BiRD). These data continue to support the role of lenalidomide-based regimens in the upfront treatment of MM. Disclosures: Mark: Celgene Corp: Speakers Bureau. Off Label Use: Lenalidomide - upfront use in myeloma. Coleman:Celgene Corp: Speakers Bureau. Zafar:Celgene Corp: Speakers Bureau. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Niesvizky:Celgene Corp: Consultancy, Speakers Bureau.

Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 536-536 ◽  
Author(s):  
Michele Cavo ◽  
Claudia Cellini ◽  
Elena Zamagni ◽  
Patrizia Tosi ◽  
Delia Cangini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
The Impact

Abstract The “Bologna 96” clinical trial was designed in an attempt to prospectively compare a single autologous transplantation (Tx-1) versus double autologous transplantation (Tx-2) as part of first-line therapy for patients with symptomatic multiple myeloma (MM) and less than 60 years of age. Tx-1 was given to support melphalan 200 mg/m2 (MEL-200); Tx-2 was given to support a first course of MEL-200 followed, within 3 to 6 months, by melphalan 120 mg/m2 + busulfan 12 mg/kg. In both arms of the study, autologous transplantation was preceded by 4 courses of VAD and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide 7 g/m2. An analysis was performed using an intent-to-treat approach on 228 patients who were randomly assigned to Tx-1 (n=115 patients, median follow-up of living patients: 45 months) or Tx-2 (n=113 patients, median follow-up of living patients: 54 months). In comparison with Tx-1, Tx-2 prolonged event-free survival (EFS) of 12 months (P=0.001) and time to progression (TTP) of 17 months (P=0.0001). Six-year projected probability of survival (OS) was 44% for Tx-1 and 63% for Tx-2 (P=0.3). The probability of attaining stringently defined complete remission (CR) or near complete remission (nCR) was 35% for Tx-1 and 48% for Tx-2; the sample size analyzed was not powered to detect a statistically significant difference between the two groups. Among patients randomized to Tx-1, attainment of CR or nCR was an essential prerequisite for extended OS (P=0.0001), EFS (P=0.000002) and TTP (P=0.000007). At the opposite, the benefits of double autologous transplantation were the greatest among patients who failed at least nCR. In particular, patients who did not attain CR or nCR after the first autologous transplantation and by study randomization received a second transplantation had a significantly longer duration of OS (P=0.01), EFS (P=0.000006) and TTP (P=0.000001) than patients who had the same response status but were assigned to receive a single autologous transplantation. Compared to Tx-1, Tx-2 significantly extended OS (P=0.04), EFS (P=0.000006) and TTP (P=0.000001) also among patients who failed Cr or nCR after receiving the entire treatment program to whom they were assigned (Tx-1 or Tx-2). At the opposite, for patients who were in CR or nCR after the first transplantation, there was no significant benefit from receiving a second autologous transplantation. In conclusion, data from the present analysis show that in comparison with a single autologous transplantation, i) double transplantation significantly prolonged EFS and TTP among younger (< 60 years) patients with previously untreated MM; ii) double autologous transplantation was of particular benefit for patients who failed at least nCR. Mature data derived from the final analysis of the study must be awaited before definite conclusions can be given concerning the impact of double autologous transplantation on the outcome of patients with MM. Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.Cavo); Ministero dell’Università e Ricerca Scientifica, progetto FIRB, RBAU012E9A_001 (M. Cavo); and Fondazione Carisbo.

A Phase II Study of Bortezomib (Velcade ®), Cyclophosphamide (Cytoxan®), Thalidomide (Thalomid®) and Dexamethasone as First-Line Therapy for Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 94-94 ◽  
Author(s):  
William Bensinger ◽  
Sundar Jagannath ◽  
Robert Vescio ◽  
Elber S. Camacho ◽  
Jeffrey Lee Wolf ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Phase Ii ◽  
Induction Therapy ◽  
Response Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Cell Harvest

Abstract Background: This phase II trial evaluated the response rate of sequential bortezomib (VELCADE®), cyclophosphamide (Cytoxan®), and dexamethasone ([VCD]; 3 cycles) followed by bortezomib, thalidomide (Thalomid®), and dexamethasone ([VTD]; 3 cycles) as first-line therapy for patients with multiple myeloma. The primary endpoints were overall response, achievement of „d very good partial response (VGPR), as well as assessment of safety and tolerability. Methods: Patients with newly diagnosed, untreated symptomatic myeloma were eligible. Treatment consisted of three 21-day cycles of bortezomib 1.3mg/m2 days 1, 4, 8, and 11, cyclophosphamide 300mg/m2 IV days 1 and 8 and dexamethasone 40mg p.o. or IV days 1, 2, 4, 5, 8, 9, 11, 12; followed by three 21-day cycles of bortezomib 1.0mg/m2 days 1, 4, 8, and 11; thalidomide 100 mg p.o. daily and dexamethasone same as cycles 1–3. Patients received thrombosis prophylaxis with ASA 325mg daily during cycles 4–6. Upon completion of the 6 cycles, patients proceeded to autologous stem cell harvest, transplant and/or maintenance therapy. Responses were defined as a decrease in serum and/or urine monoclonal (M) protein by 50% or greater. VGPR and other responses were as per the International Response Criteria. Results: This report provides results for all 44 eligible patients: median age 59 years; 68% male; 61% Stage III (D/S); documented ISS Stage II/III 59%; IgG 66%, IgA 17%; 17% light chain only. To date the first 30 patients are fully evaluable for response with 28-day post therapy follow up. The overall response rate (ORR; ≥PR) is 90% with 18/30 (60%) achieving CR + VGPR (CR 33%); 9/30 (30%) PR and 3/30 (10%) stable disease or not evaluable. Overall, both components of the sequential regimen were very well tolerated. One patient had a ruptured colonic diverticulum possibly related to dexamethasone, but recovered well and achieved VGPR on trial. There have been 49 therapy attributed toxicity events which have required drug/schedule adjustments. Of these, 9 events were Gd 3/4: 3 attributed to cyclophosphamide, 3 to dexamethasone, 2 attributed to bortezomib and 1 to thalidomide. DVT occurred in one patient who was at high risk because of prior bilateral hip surgery. Fourteen patients have proceeded to successful stem cell harvest and autologous transplant. Post transplant follow up as well as response information for all 44 patients will be presented. Conclusion: This bortezomib/cyclophosphamide/dexamethasone (VCD) based combination induction therapy followed by VTD is a promising addition to the treatment armamentarium for previously untreated patients. The response rates: ORR 90%; □ VGPR (60%) and CR (33%) are extremely encouraging and improve over our bortezomib/dexamethasone 2-drug experience which produced 90% □ PR and 38% □ VGPR. This very well tolerated new regimen is potentially an important step forward in induction therapy with presentation of more mature data. Supported by the Aptium Oncology Research Network and a research grant from Millennium Pharmaceuticals, Inc.

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