Response-Adapted Sequential Azacitidine and Induction Chemotherapy in Patients > 60 Years Old with Newly Diagnosed AML Eligible for Chemotherapy (RAS-AZIC): First Data of the Interim Analysis of the DRKS00004519 Study of the East German Study Group (OSHO)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1346-1346
Author(s):  
Haifa Kathrin Al-Ali ◽  
Nadja Jaekel ◽  
Karolin Hubert ◽  
Rainer Krahl ◽  
Mathias Haenel ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Interim Analysis ◽  
Research Funding ◽  
Data Monitoring Committee ◽  
Patient Characteristics ◽  
Primary Objective ◽  
Epigenetic Therapy ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Impact

Abstract The prognosis of AML in patients (pts) >60 years (y) is poor and there is no universally accepted standard approach. After induction chemotherapy (IC), a complete remission (CR+CRi) rate of 56.4% and a mortality of 21% at day (d) 90 are expected (Niederwieser et al, ASH 2012). Azacitidine (AZA) yields a one-year survival (OS) rate of 46.5% in pts >65 y and >30% marrow (BM) blasts (Dombret et al, Blood 2015). Yet, AZA and IC are not mutually exclusive. First results of the interim analysis of the DRKS00004519 (RAS-AZIC) study which evaluates priming with AZA followed by AZA or IC in pts >60 y with AML are presented. Patients and methods: Major inclusion criteria are newly diagnosed AML with marrow blasts >20% by aspiration or biopsy irrespective of WBC count, age >60 y, and eligibility for IC. Secondary AML from an antecedent hematologic disorder and therapy-related AML are not excluded. In the phase I part of the trial, safety of priming with AZA (75 mg/m2/day s.c) for 7 d followed by IC (Mitoxantrone 10 mg/ m2/day d 1-3 and cytarabine 1 g/m2/BID d 1, 3, 5, 7) on d 17 was established through a 3+3 design. In the multicenter phase II part (figure), priming was sequentially followed by AZA or IC based on d 15 BM blasts and d 56 response which were identified as early predictors for long-term response to AZA in AML (Al-Ali et al., Leuk Lymph 2012). The primary objective is overall response (OR) which includes CR, CRi, and PR at d 90 according to the International Working Group criteria (Cheson et al, J Clin Oncol 2003). Safety, OS, and mortality were secondary end points. According to the optimal two-stage design (Simon, Control Clin Trials 1989), an expected OR of 61% at the end of trial was estimated. Thus in a first stage analysis, < 19 of consecutive 40 (47.5%) pts not achieving the primary objective would be considered an indication for inferiority of the protocol treatment compared to standard IC. Hence, an interim analysis of the first stage was planned per protocol while accrual continues to include the first 40 pts who received the maximal tolerated priming dose of AZA. The trial is supervised by an independent Data Monitoring Committee. Adverse events (AEs) are reported according to the NCI CTCAE 4.03. All pts gave written informed consent. Results: Patient characteristics are shown in table 1. Median age is 69 y and median blast count 39%. All pts received priming with AZA. Median BM blasts at d 15 was 27% (range 2.4-88%). To date, data on subsequent therapies are captured in 33 (82.5%) pts. Except for one (withdrew consent on d 27), all pts received protocol assigned treatment based on BM blasts on d 15 [17/32 (53%) continued with AZA, 15/32 (47%) received IC]. Likewise, 26/32 (81%) pts ([2x data not yet available, 2x death (d 34; d 53), and 2x physician's choice] received response-adapted treatment on d 56 [12/26 (46%) started AZA maintenance and 14/26 (55%) received IC]. OR at d 90 for the 26 as yet evaluable pts is 80.7% [CR (61.5%, n=16); CRi (11.5%, n=3); PR (7.7%, n=2). No additional mortality till d 90 was reported. For the entire cohort, 85% of pts are alive after a median follow-up of 6 months. AEs were consistent with the known safety profile of AZA and IC. AEs > grade 3 were reported 83x in 20 (50%) pts being mainly infectious and respiratory complications (60%). As expected, the majority (57%) were reported under IC, followed by 19% and 17% under priming and the 2. AZA cycle respectively. AEs led to postponement of the planned therapy in 6 pts (3x IC on d 17, 2x 2. AZA, 1x IC on d 56). The final assessment of the interim analysis is set in the near future. Conclusions: These data imply that in a heterogeneous disease like AML, integrating epigenetic therapy with chemotherapy in elderly pts in an individualized response-based approach is feasible, induces responses at least comparable to those seen after IC, and is associated with a remarkable low mortality. The definitive response rate and the impact of such an approach on survival will be answered at the end of the trial. Table 1. Patient characteristics (n=40) Median age, range (years) 69 ( 61 - 82) Male/Female (%) 55 / 45 Baseline ECOG (%)0/1/2 21 / 63 / 16 Type of AMLDo novo/secondary (%) 61 /39 Median WBC (range) x 109/L 6.7 (0.7 - 81.8 ) Median bone marrow blasts (aspiration) (range) (%) 39 (13 - 90) Cytogenetics (n=35)Normal/intermediate/unfavourable (%) 54 /23 / 23 FLT3+ (n=34) (%) 9 NPM1 + (n=34) (%) 9 Figure 1. Figure 1. Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Off Label Use: Azacitidine is not approved for the use in patients with AML and blasts > 30% outside clinical trials.

The Impact of Distance to Treatment Center on the Outcome of AML

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4742-4742 ◽  
Author(s):  
Bruno C. Medeiros ◽  
Tamara J. Dunn ◽  
Holbrook E Kohrt ◽  
Steven Coutre ◽  
Jason Gotlib ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Adverse Outcomes ◽  
Treatment Center ◽  
P Value ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Impact

Abstract Abstract 4742 Introduction While the distance patients travel to a treatment center (DTC) adversely impacts survival of patients with trauma, cardiac, or neurological disorders, as well as certain solid tumors, less is known of its influence in acute myeloid leukemia (AML). Care for patients with AML involves frequent emergent and urgent management, often complicating primary therapy provided in distant tertiary referral centers. We therefore hypothesized that increased DTC has a negative impact on outcome. We tested this hypothesis by assessing the effect of DTC on survival of patients with AML receiving care at a single institution. Patients and Methods Within the Stanford Leukemia Database, we identified 884 consecutive adult patients between 1993 and 2009 meeting the following criteria: age >=18, newly diagnosed AML (excluding APL), clinical management at Stanford University Medical Center (SUMC), and verified residence location available for DTC determination. Of these, 571 were deemed fit by the admitting physician to receive myelosuppressive induction chemotherapy. DTC was calculated by straight-line journey distance between home address at the time of diagnosis and treatment center. Results The median age for the entire cohort is 55 years and 322 patients (36%) are older than 60 years of age. Median survival for the entire cohort was 14.0 months. DTC was not univariately associated with outcome as a continuous variable. When testing for a critical DTC threshold impacting outcomes across the entire cohort, we found a significant correlation between longer DTC and adverse outcomes, shorter DTC was associated with lower OS. Patients living within 20 miles of SUMC had a worse median overall survival (10.4 months versus 15.0 months, HR 1.23, corrected p-value 0.02). However, when adjusted for administration of induction chemotherapy (p<0.0001), age at presentation (p<0.0001) and karyotype at diagnosis (CBF vs other; p-value- 0.92), the negative impact of DTC was lost (p=0.08). Conclusion After accounting for confounding factors, DTC has no significant impact on the outcome of newly diagnosed AML patients receiving care at our institution. Unlike non-hematologic malignancies, distance to treatment center likely does not adversely influence outcomes for patients with AML. Disclosures: No relevant conflicts of interest to declare.

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

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

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

scholarly journals Prognostic Impact of Time from Diagnosis to Initial Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3981-3981
Author(s):  
Yoshimasa Kamoda ◽  
Akira Hangaishi ◽  
Hiroki Hayashida ◽  
Yusuke Uchibori ◽  
Hiromitsu Iizuka ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Initial Treatment ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Progressive Disease ◽  
Newly Diagnosed ◽  
Wbc Count ◽  
The Impact ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) has been considered as oncologic emergency and therefore, immediate initiation of chemotherapy is common in clinical practice. On the other hand, waiting until cytogenetic and molecular results return could offer individualized therapies according to the risk stratifications of AML based on cytogenetic or molecular abnormalities. There are few data on the impact of delaying induction chemotherapy on the prognosis of AML. According to one study, time from diagnosis to initial treatment (TDT) of more than 5 days had adverse impact on younger AML patients, but not older patients (Sekeres et al. Blood 2009). Another study showed TDT had no impact on overall survival (OS) at all age (Bertoli et al. Blood 2013). We retrospectively analyzed the impact of TDT on outcome of newly diagnosed AML patients in our institution. Methods: This study included 145 newly diagnosed non-M3 AML patients who were treated with induction chemotherapy in our institution between 2008 and 2017. Patients received various kinds of induction therapy including anthracycline, cytarabine, azacitidine and investigational drugs as initial therapy. Associations of TDT with patient characteristics available at diagnosis and complete remission (CR) rate and OS were examined. Results: The median age was 66 years (range, 18-88) and the median TDT was 1 day (range, 0-91). Cytogenetic risk group was favorable in 13 (9%), intermediate in 93 (64%) and adverse in 39 (27%) according to Medical Research Council cytogenetic classification. NPM1 mutation was detected in 11 of 38 (29%) evaluable patients and FLT3-ITD was in 8 of 45 (18%). Shorter TDT was significantly associated with progressive disease including younger age, poor performance status, de novo AML, elevated white blood cell (WBC) count, elevated percentage of bone marrow blasts, elevated lactate dehydrogenase levels (all P < 0.05). CR rate was 52% and median OS was 431 days. TDT had significant impact on CR rate (P = 0.004) but not OS (P = 0.978). However, after adjustment for age, cytogenetic risk groups and WBC count, the association with both CR rate and OS was not significant (P = 0.581 and P = 0593, respectively). Furthermore, TDT was not associated with early death in univariate analysis (p = 0.186). Conclusion: TDT is significantly associated with progressive disease, but not with outcome in newly diagnosed AML. These results suggest that, except for special situations, delaying initial treatment by a short period of time to wait for the results of laboratory tests may be acceptable, allowing for individual therapies. To verify the prognostic effect of TDT, further investigation in a larger cohort is required. Disclosures: No relevant conflicts of interest to declare. Disclosures Usuki: Ono Pharmaceutical: Speakers Bureau; Novartis: Speakers Bureau; SymBio Pharmaceuticals Limited.: Research Funding; Pfizer Japan: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Boehringer-Ingelheim Japan: Research Funding; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; GlaxoSmithKline K.K.: Research Funding; Janssen Pharmaceutical K.K: Research Funding; Celgene Corporation: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding; Shire Japan: Research Funding; Takeda Pharmaceutical: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Nippon Shinyaku: Speakers Bureau; Mochida Pharmaceutical: Speakers Bureau; MSD K.K.: Speakers Bureau.

scholarly journals Incidence of CDI and Association with Antibiotics in a Cohort of Patients with Newly Diagnosed Acute Myeloid Leukemia Receiving Induction Chemotherapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-42
Author(s):  
Carolin Jakob ◽  
Aurélie Bauquet ◽  
Renaud Buffet ◽  
Maria Vehreschild ◽  
Janne Vehreschild
Keyword(s):  
Internal Medicine ◽  
Induction Chemotherapy ◽  
Research Funding ◽  
Bacterial Infections ◽  
German Society ◽  
University Hospital ◽  
Newly Diagnosed ◽  
Observational Period ◽  
Binary Logistic Regression Model ◽  
Acute Myeloid

Background:Because bacterial infections are a common complication during neutropenia and a major cause for morbidity and mortality, patients with Acute Myeloid Leukaemia (AML) often receive prolonged courses of broad-spectrum antibiotics during induction chemotherapy. This extended exposure to antibiotics deeply disrupts the gut microbiota and may result in its colonization by resistant, opportunistic and potentially pathogenic microbes.Clostridioides difficile (C.difficile)is one such bacteria often found in patients whose microbiota has been strongly disrupted. Aim:The purpose of this study was to measure the incidence ofC. difficileinfection (CDI) in newly diagnosed AML patients who received induction chemotherapy and to evaluate the association between CDI and the use of antibiotics. Methods:We retrospectively studied the medical history of patients treated from 01/2016 to 12/2018 at the Department of Internal Medicine I of the University Hospital Cologne. The observational period was defined as 100 successive days after onset of induction chemotherapy or from onset of induction chemotherapy until microbiological confirmed CDI, or until death, whichever event occurred first. The diagnosis of CDI was confirmed by microbiological findings indicating the presence of toxin-producingC. difficilein stool isolates of symptomatic patients. The associations between therapeutic and prophylactic antibiotics and CDI were determined by use of a multivariable backward-stepwise binary logistic regression model. Findings:133 patients were included in the study. 30 patients developed CDI during the study period. 5 patients had two episodes or more. The incidence rate for CDI per 10,000 patient days in the observational period was 29.9. The incidence rates of CDI for the period after onset of induction chemotherapy reached 10.5% (n=14) at 8 weeks and 18.8% (n=25) at 120 days. In the analysis, we could not identify a specific antibiotic as risk factor for CDI but the result may be biased by the different mean observational periods for the group with and without CDI (the observational period for the group with CDI ends at the day of CDI). Conclusions:CDI is a frequent comorbidity affecting patients with newly diagnosed AML and receiving induction chemotherapy and deserves the attention of the medical teams in charge of the patients for adequate prevention and treatment approaches. Disclosures Bauquet: Da Volterra:Current Employment.Buffet:Da Volterra:Current Employment;Alfa Collaborative Group:Current Employment.Vehreschild:Berlin Chemie:Consultancy, Honoraria;Organobalance:Research Funding, Speakers Bureau;Pfizer:Research Funding, Speakers Bureau;Da Volterra:Research Funding;Seres Therapeutics:Research Funding;Astellas Pharma:Consultancy, Honoraria, Research Funding, Speakers Bureau;3M:Research Funding;Gilead:Research Funding, Speakers Bureau;MSD/Merck:Consultancy, Honoraria, Research Funding, Speakers Bureau;Basilea:Speakers Bureau.Vehreschild:Rigshospitalet Copenhagen:Research Funding;Academy for Infectious Medicine:Honoraria;University Manchester:Honoraria;German Society for Infectious Diseases (DGI):Honoraria;Ärztekammer Nordrhein:Honoraria;University Hospital Aachen:Honoraria;Back Bay Strategies:Honoraria;German Society for Internal Medicine (DGIM):Honoraria;Merck / MSD:Research Funding;Gilead:Research Funding;Pfizer:Research Funding;Astellas Pharma:Research Funding;Basilea:Research Funding;German Centre for Infection Research (DZIF):Research Funding;), German Federal Ministry of Education and Research (BMBF):Research Funding;(PJ-T: DLR):Research Funding;University of Bristol:Research Funding;Merck/MSD:Honoraria;Gilead:Honoraria;Pfizer:Honoraria;Astellas Pharma:Honoraria;Basilea:Honoraria;German Centre for Infection Research (DZIF):Honoraria;University Hospital Freiburg/ Congress and Communication:Honoraria.

scholarly journals The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4359-4359
Author(s):  
Koji Sasaki ◽  
Rashmi Kanagal-Shamanna ◽  
Guillermo Montalban-Bravo ◽  
Rita Assi ◽  
Kiran Naqvi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Risk Of Death ◽  
Genetics Research ◽  
The Impact ◽  
Generation Sequencing

Abstract Introduction: Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy. Methods: From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencing was performed on the bone marrow samples to detect the presence of CHIP-associated mutations defined as DNMT3A, TET2, ASXL1, JAK2 and TP53. Overall survival (OS) was defined as time period from the diagnosis of AML to the date of last follow-up or death. Univariate (UVA) and multivariate Cox proportional hazard regression (MVA) were performed to identify prognostic factors for OS with p value cutoff of 0.020 for the selection of variables for MVA. Landmark analysis at 6 months was performed for the evaluation of the impact of clearance of CHIP, FLT3-ITD, FLT3D835, and NPM1 mutations. Results: We identified 378 patients (74%) with AML with CHIP mutations; 134 patients (26%) with AML without CHIP mutations. The overall median follow-up of 23 months (range, 0.1-49.0). The median age at diagnosis was 70 years (range, 17-92) and 66 years (range, 20-87) in CHIP AML and non-CHIP AML, respectively (p =0.001). Of 371 patients and 127 patients evaluable for cytogenetic in CHIP AML and non-CHIP AML, 124 (33%) and 25 patients (20%) had complex karyotype, respectively (p= 0.004). Of 378 patients with CHIP AML, 183 patients (48%) had TET2 mutations; 113 (30%), TP53; 110 (29%), ASXL1; 109 (29%), DNMT3A; JAK2, 46 (12%). Of 378 patients, single CHIP mutations was observed in 225 patients (60%); double, 33 (9%); triple, 28 (7%); quadruple, 1 (0%). Concurrent FLT3-ITD mutations was detected in 47 patients (13%) and 12 patients (9%) in CHIP AML and non-CHIP AML, respectively (p= 0.287); FLT3-D835, 22 (6%) and 8 (6%), respectively (p= 0.932); NPM1 mutations, 62 (17%) and 13 (10%), respectively (p= 0.057). Of 183 patients with TET2-mutated AML, the median TET2 variant allele frequency (VAF) was 42.9% (range, 2.26-95.32); of 113 with TP53-mutated AML, the median TP53 VAF, 45.9% (range, 1.15-93.74); of 109 with ASXL1-mutated AML, the median ASXL1 VAF was 34.5% (range, 1.17-58.62); of 109 with DNMT3A-mutated AML, the median DNMT3A VAF was 41.8% (range, 1.02-91.66); of 46 with JAK2-mutated AML, the median JAK2 VAF was 54.4% (range, 1.49-98.52). Overall, the median OS was 12 months and 11 months in CHIP AML and non-CHIP AML, respectively (p= 0.564); 16 months and 5 months in TET2-mutated AML and non-TET2-mutated AML, respectively (p <0.001); 4 months and 13 months in TP53-mutated and non-TP53-mutated AML, respectively (p< 0.001); 17 months and 11 months in DNMT3A-mutated and non-DNMT3A-mutated AML, respectively (p= 0.072); 16 months and 11 months in ASXL1-mutated AML and non-ASXL1-mutated AML, respectively (p= 0.067); 11 months and 12 months in JAK2-murated and non-JAK2-mutated AML, respectively (p= 0.123). The presence and number of CHIP mutations were not a prognostic factor for OS by univariate analysis (p=0.565; hazard ratio [HR], 0.929; 95% confidence interval [CI], 0.722-1.194: p= 0.408; hazard ratio, 1.058; 95% confidence interval, 0.926-1.208, respectively). MVA Cox regression identified age (p< 0.001; HR, 1.036; 95% CI, 1.024-1.048), TP53 VAF (p= 0.007; HR, 1.009; 95% CI, 1.002-1.016), NPM1 VAF (p=0.006; HR, 0.980; 95% CI, 0.967-0.994), and complex karyotype (p<0.001; HR, 1.869; 95% CI, 1.332-2.622) as independent prognostic factors for OS. Of 33 patients with CHIP AML who were evaluated for the clearance of VAF by next generation sequencing , landmark analysis at 6 months showed median OS of not reached and 20.3 months in patients with and without CHIP-mutation clearance, respectively (p=0.310). Conclusion: The VAF of TP53 and NPM1 mutations by next generation sequencing can further stratify patients with newly diagnosed AML. Approximately, each increment of TP53 and NPM1 VAF by 1% is independently associated with 1% higher risk of death, and 2% lower risk of death, respectively. The presence of CHIP mutations except TP53 does not affect outcome. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Ravandi:Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Sunesis: Honoraria; Xencor: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria. Kadia:BMS: Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Research Funding. DiNardo:Karyopharm: Honoraria; Agios: Consultancy; Celgene: Honoraria; Medimmune: Honoraria; Bayer: Honoraria; Abbvie: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.

VELCADE/Dexamethasone (Vel/Dex) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): An Interim Analysis of the IFM 2005-01 Randomized Multicenter Phase III Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 56-56 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Gerald Marit ◽  
Denis Caillot ◽  
Philippe Casassus ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Interim Analysis ◽  
Primary Objective ◽  
Phase Iii ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Β2 Microglobulin

Abstract ASCT is considered the standard of care for patients up to 65 years of age with MM. The optimal induction treatment prior to ASCT is still unknown. VAD is a commonly used regimen but is associated with a number of toxicities, administrative inconvenience, and a complete remission (CR) rate of typically less than 10%. Recently the combination thalidomide/Dex was reported to induce a higher overall response rate than Dex alone in newly diagnosed patients, but with significantly more toxicities, especially deep vein thrombosis, and a 4% CR rate (Rajkumar et al, J Clin Oncol 2006;24:431–6). In a phase II trial we have evaluated the combination of Vel 1.3mg/m2 D1, 4, 8, 11 with Dex 40mg/D D1-4, D9-12, for 4 consecutive 21-D cycles (Dex only on D1-4 during cycles 3–4). This combination was well tolerated and yielded a 21% CR/nCR rate with successful stem cell harvest and engraftment (Harousseau et al, Haematologica 2006). In 2005, the IFM initiated a multicenter randomized phase III trial comparing Vel/Dex with VAD as induction treatment of patients with newly diagnosed MM up to the age of 65. The primary objective of the study is the CR (negative immunofixation) plus nCR (CR but positive immunofixation) rate after 4 cycles. A secondary objective is to evaluate the role of consolidation with 2 courses of DCEP (Dex, cyclophosphamide, etoposide, cisplatin). Patients were randomized at diagnosis among 4 arms (A1: 4 cycles of VAD; A2: 4 cycles of VAD + 2 cycles of DCEP; B1: 4 cycles of Vel/Dex; B2: 4 cycles of Vel/Dex + 2 cycles of DCEP); stratification was by cytogenetics and β2 microglobulin. Stem cell collection was performed between cycle 3 and cycle 4 after priming with G-CSF (10μg/kg/D × 6 D). At the end of induction (± DCEP consolidation) treatment, patients received melphalan 200mg/m2 plus ASCT. Enrollment of 480 patients is planned, to detect a 10% higher CR/nCR rate with Vel/Dex (20% vs 10%) with 80% power (two-sided test, significance level 0.05). An interim analysis is planned when 222 patients have been evaluated for response at the end of induction. As of July 2006, 304 patients have been enrolled. Randomization of the 222 patients to be considered for interim analysis was completed on May 19th. Baseline characteristics include: median age 55y; 140M, 82F; β2 microglobulin >3mg/L in 54%; del13 by FISH in 45%. The occurrence of serious adverse events (SAEs) was similar between the VAD and Vel/Dex arms (31% with VAD, 33% with Vel/Dex). The most frequent SAEs were pneumopathy (5.3% VAD, 4.0% Vel/Dex), thrombosis (2.7% VAD, 3.3% Vel/Dex), and peripheral neuropathy (1.3% VAD, 3.3% Vel/Dex). We intend to present results from the interim analysis.

A Phase 2 Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) Plus Rituximab in Newly Diagnosed, Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3957-3957
Author(s):  
Mark Kirschbaum ◽  
Leslie Popplewell ◽  
Maria L Delioukina ◽  
Robert w Chen ◽  
Vinod Pullarkat ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Interim Analysis ◽  
Research Funding ◽  
Hydroxamic Acid ◽  
Marginal Zone ◽  
Newly Diagnosed ◽  
Deacetylase Inhibitor ◽  
Mantle Cell ◽  
Indolent Lymphomas

Abstract Abstract 3957 Background: The indolent (follicular, marginal zone and mantle cell) lymphomas tend to recur with decreasing intervals of remission after standard chemotherapy. New modalities of treatment are necessary. Vorinostat (SAHA) is an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deacetylases. An earlier study of single agent vorinostat showed promising activity in indolent lymphomas, thus a follow up study combining vorinostat with rituxan was performed. Methods: We report the results of the planned interim analysis (first stage) of a two-stage phase II study of oral vorinostat combined with rituximab in patients with newly diagnosed, relapsed or refractory (to chemotherapy and/or rituximab) follicular, marginal zone, or mantle cell lymphoma. Vorinostat is given at 200 mg PO twice daily for 14 consecutive days on a 21 day cycle. Rituximab is given on day one of each cycle. CT scanning and/or FDG-PET are performed after every three cycles, as is marrow biopsy for those with marrow involvement at time of entry into study. Patients may have received up to four prior chemotherapy regimens including tositumomab or ibritumomab; previous transplant is allowed. 17 eligible patients (8 female, 9 male) were accrued during the first stage of accrual. The median age at treatment was 60 years (range 44–71). Histologies represented: mantle cell (MC)-2, marginal zone (MZL)-1, and follicular lymphoma (FL)-14. Treatment was well tolerated. Grade 4 toxicities possibly attributable to study drug include neutropenia (n=1), thrombosis (n=3), and platelet (n=1). Grade 3 possibly related toxicities include fatigue (n=5), hyperglycemia (n=3), dehydration (n=2), and one each of platelets, hypophosphatemia, hypotension, infection, diarrhea, syncope, and thrombosis (nonclinical pulmonary embolism discovered incidentally on CT scan). Results: The overall formal response (CR+PR) rate thus far is 35% (6/17), with a response rate of 43% (6/14) for patients with FL, and no formal responses seen in mantle cell (0/2) or MZL (0/1). By the current Cheson criteria, 5 patients achieved complete remission (CR), and 1 patients achieved partial remission (PR). One patient (FL) with a CR relapsed 14 months after treatment initiation. The remaining 5 responders have not relapsed, at 4, 9, 13, 16 and 21 months. The median PFS has not been reached, and only 1 responder has progressed to date at 9 months (patient with FL). Conclusions: The combination of the histone deacetylase inhibitor vorinostat with rituximab is well tolerated, and shows encouraging activity against relapsed/refractory indolent lymphoma The study has passed interim analysis and will proceed to full accrual of 33 patients. Support: Supported in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. Disclosures: Kirschbaum: Merck: Honoraria, Research Funding. Off Label Use: clinical trial of vorinostat in indolent lymphomas. Pullarkat:Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau.

ENESTnd Update: Nilotinib (NIL) Vs Imatinib (IM) In Patients (pts) With Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) and The Impact Of Early Molecular Response (EMR) and Sokal Risk At Diagnosis On Long-Term Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 92-92 ◽  
Author(s):  
Giuseppe Saglio ◽  
Andreas Hochhaus ◽  
Timothy P. Hughes ◽  
Richard E. Clark ◽  
Hirohisa Nakamae ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Eligibility Criterion ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Vascular Events ◽  
Advisory Committees ◽  
The Impact

Abstract Introduction Frontline NIL continues to show benefit over IM in pts with Philadelphia chromosome-positive (Ph+) CML-CP, with higher rates of major molecular response (MMR; BCR-ABLIS ≤ 0.1%) and MR4.5 (BCR-ABLIS ≤ 0.0032%), lower rates of progression to accelerated phase (AP)/blast crisis (BC) and fewer new BCR-ABL mutations on treatment in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Pts (ENESTnd) trial. Here, we report data with a minimum follow-up (f/u) of 4 y; updated data based on 5 y of f/u will be presented. Methods Adults with newly diagnosed Ph+ CML-CP (N = 846) were randomized to NIL 300 mg twice daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once daily (QD; n = 283). Progression and overall survival (OS) events were collected prospectively during study f/u, including after discontinuation of study treatment. Efficacy in the NIL 300 mg BID and IM arms was evaluated based on achievement of EMR (BCR-ABLIS ≤ 10% at 3 mo). Results At 4 y, ≥ 87% of pts remained on study in each arm and 57%-69% remained on core treatment (Table). Rates of MMR and MR4.5 by 4 y were significantly higher with NIL vs IM. Significantly fewer pts progressed to AP/BC on NIL vs IM (on core treatment: 0.7%, 1.1%, and 4.2%; on study: 3.2%, 2.1%, and 6.7% [NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively]). Of 17 pts across the 3 arms who progressed on core treatment, 11 (65%) had never achieved complete cytogenetic response and none had achieved MR4.5. Fewer mutations have emerged in the NIL arms vs the IM arm; in y 4, mutations emerged in 2 pts (1 pt with T315I on NIL 300 mg BID; 1 pt with F317L on IM). More pts achieved EMR in the NIL 300 mg BID arm vs the IM arm (91% vs 67%). Pts with EMR had significantly higher rates of progression-free survival (PFS) and OS at 4 y vs pts with BCR-ABL > 10% at 3 mo. Among pts with BCR-ABL > 10% at 3 mo, more progressions to AP/BC occurred in the IM arm (n = 14) vs the NIL 300 mg BID arm (n = 2); half of these pts progressed between 3 and 6 mo. In pts with intermediate or high Sokal risk, PFS and OS at 4 y were higher in both NIL arms vs the IM arm. No new safety signals were detected. Selected cardiac and vascular events were more common on NIL vs IM (by 4 y, peripheral arterial occlusive disease [PAOD] in 4 [1.4%], 5 [1.8%], and 0 pts; ischemic heart disease [IHD] in 11 [3.9%], 14 [5.1%,] and 3 [1.1%] pts; and ischemic cerebrovascular events in 3 [1.1%], 5 [1.8%], and 1 [0.4%] pts in the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively). In the NIL 300 mg BID arm, 2 of 11 IHD events occurred between 3 and 4 y (all 4 PAOD events occurred in the first 2 y). In the NIL 400 mg BID arm, 2 of 5 PAOD events and 3 of 14 IHD events occurred between 3 and 4 y. Most pts (7 of 9) with a PAOD event on NIL were at high risk due to a combination of baseline risk factors. Conclusions NIL, a standard-of-care frontline therapy option for newly diagnosed CML-CP pts, affords superior efficacy compared with IM, including higher rates of EMR (which is associated with improved long-term outcomes), higher rates of MR4.5 (a key eligibility criterion for many studies of treatment-free remission), and a lower risk of disease progression. NIL continues to show good tolerability with long-term f/u. While selected cardiac and vascular events (including PAOD) are slightly more frequent on NIL vs IM, no increase in annual incidence of these events over time has been observed. Disclosures: Saglio: ARIAD: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Hochhaus:Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Hughes:Ariad: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CSL: Research Funding. Clark:Pfizer: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau. Nakamae:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau, travel/ accomodations/ meeting expenses Other. Kim:BMS, Novartis,IL-Yang: Honoraria; Pfizer: Consultancy, Research Funding. Etienne:Pfizer: Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Flinn:Novartis: Research Funding. Lipton:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Moiraghi:Bristol Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Fan:Novartis: Employment. Menssen:Novartis: Employment. Kantarjian:Novartis: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; ARIAD: Research Funding. Larson:Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy.

Interim Analysis Of The Mmrf Commpass Trial, a Longitudinal Study In Multiple Myeloma Relating Clinical Outcomes To Genomic and Immunophenotypic Profiles

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 532-532 ◽  
Author(s):  
Jonathan J Keats ◽  
David W Craig ◽  
Winnie Liang ◽  
Yellapantula Venkata ◽  
Ahmet Kurdoglu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Personalized Medicine ◽  
Interim Analysis ◽  
Research Funding ◽  
Residual Disease ◽  
Fusion Gene ◽  
Eligible Patient ◽  
Comprehensive Analysis ◽  
Newly Diagnosed ◽  
Fusion Transcripts

Abstract The Multiple Myeloma Research Foundation (MMRF) CoMMpass trial is the cornerstone of the MMRF Personalized Medicine Initiative. The accrual goal is 1000 patients with newly-diagnosed active multiple with sufficient tumor material for the comprehensive analysis of each tumor genome. Each eligible patient will be followed from initial diagnosis longitudinally for a minimum of 8 years. Additional tumor samples will be collected and comprehensively analyzed when possible for each patient at time of suspect CR, recurrence or progression of disease. The clinical study (NCT0145429) opened in July 2011 and now includes 56 sites in the US and Canada that have enrolled over 300 patients as of Aug. 1, 2013. The frontline treatments permitted in this study include current standard of care therapies containing a proteasome inhibitor, an IMiD or both. The comprehensive analysis of each tumor and matched normal genome involves; Long-Insert Whole Genome Sequencing (WGS) to identify somatic copy number alterations and structural changes, Whole Exome Sequencing (WES) to identify somatic single nucleotide variants and indels, and RNA sequencing (RNAseq) to define transcript expression levels and fusion transcripts. In addition, BRAF pyrosequencing and immunophenotyping analysis are being done in CAP-CLIA certified labs. An extensive, open-access, public clinical and molecular database, the CoMMpass Researcher Gateway (RG) (https://research.themmrf.org), is being developed to facilitate the rapid dissemination of the results and provides the myeloma community with a mechanism to analyze the results. The clinical endpoints and outcomes also include Quality of Life measures and health care resource utilization. An initial interim analysis on the first 178 cases has just been completed and made publicly available through the CoMMpass RG. At the molecular level, BRAF analysis on this serial sample set of newly diagnosed patients identified V600E mutations at rate of 5.7%, confirming our previous observations from a mixture of non-consecutive treated and untreated patient samples in our previous genomic efforts. The flow cytometry panel was designed to provide a comprehensive immunofingerprint of each patient that could be used for minimal residual disease monitoring and to monitor potentially therapeutic options; MS4A1/CD20, CD52, KIT/CD117, and FGFR3. These studies have identified tumors which are 100% positive for these actionable antigens at frequencies of; 16.0% for CD20, 5.7% for CD52, 49.7% for CD117, and 8.5% for FGFR3. Of the 178 cases, 34 were profiled through WGS, WES and RNAseq before this interim analysis. We identified 553 variants (median 19 per patient, range 11-55) were the variant allele detected by WES was also detected by RNAseq, suggesting the variant is potentially biologically relevant. Of these genes, 36 were seen more than once and 7 were identified in three or more patients. This includes NRAS (23.5%), KRAS (14.7%), BRAF (8.8%), DIS3 (8.8%), FAM46C (8.8%), TRAF3 (8.8%), and ZNF100 (8.8%). Interestingly, all three ZNF100 variants show preferential expression of the mutant allele. Within this cohort the only recurrent fusion gene identified is the classic IgH-MMSET fusion transcripts associate with t(4;14). The MMRF CoMMpass is providing unprecedented molecular characterization and correlating clinical datasets that will help define the determinants of response to anti-myeloma agents, reveal new, actionable targets and/or those shared with other cancers and facilitate future clinical trial designs, thus serving as a stepping stone toward personalized medicine for myeloma patients. Disclosures: Auclair: MMRC: Employment. Harrison:MMRC: Employment. Jagannath:Celgene: Honoraria; Millennium: Honoraria. Siegel:Celgene: Honoraria, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria, Speakers Bureau. Vij:Celgene: Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria, Research Funding, Speakers Bureau. Zimmerman:Celgene: Honoraria; Millenium: Honoraria; Onyx: Honoraria. Capone:MMRC: Employment. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.

Meta-Analytic Summary of the Burden of Pain and Fatigue in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5967-5967
Author(s):  
Peter C. Trask ◽  
Mark Atkinson ◽  
Bhumi Trivedi ◽  
Andrew Palsgrove ◽  
William Benton Jones ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity Analysis ◽  
Research Funding ◽  
Meta Analysis ◽  
Clinical Group ◽  
Common Symptom ◽  
Newly Diagnosed ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
The Impact

Abstract Aims: Multiple myeloma (MM) is a hematologic malignancy of plasma cells. Bone disease is a characteristic symptom of MM, and pain is one of its most distressing features. Anemia is also a common symptom and is manifested as fatigue and tiredness among MM patients. We conducted a systematic review and meta-analysis of the EORTC QLQ-C30 pain and fatigue scales in two clinical MM populations (one with newly-diagnosed MM and a second undergoing medical management with re-emergent or advanced myeloma) to more precisely quantify the burden of pain and fatigue in MM. Methods: Studies assessing pain and fatigue in MM were identified through a search of specific terms in the medical-subject headings and keywords in PubMed. Inclusion criteria were English-language studies published between January 1, 1996, and July 1, 2014; diagnosis of MM; and availability of data on pain and/or fatigue as measured by the EORTC QLQ-C30. Full-text articles from germane abstracts were retrieved for eligibility assessment, and 27 articles were selected for inclusion in the analysis. Two groups of peer-reviewed articles were created: one consisting of publications that focused on newly-diagnosed MM and the other consisting of articles involving MM patients with advanced conditions, including those who had a disease recurrence or were receiving autologous bone marrow transplantation. The mean values and standard deviations (SDs) were recorded across all publications irrespective of sex, age, and stage of illness. Of the 27 studies, 17 did not report standard error (SE) or SD values associated with EORTC QLQ-C30 pain and fatigue scales. These missing values were estimated using the overall average of SDs for that scale observed across all studies within the publication group (either newly-diagnosed or recurrent/advanced disease). A sensitivity analysis was conducted to compare the pooled mean and SEs associated with results obtained with and without the SD imputation procedure. The means and SDs from the two sets of publications were entered into Comprehensive Meta-analysis™ with both scales (pain or fatigue) and existing or imputed SDs as grouping variables. The summary means and confidence intervals for each scale by clinical group were computed by weighting the individual studies by sample size and were statistically summarized based on a fixed-effect model. Results: The EORTC QLQ-C30 fatigue and pain scales range from 0-100 with higher scores indicating greater symptoms (i.e., more fatigue and pain). The overall mean across the 27 publications was 47.1 for fatigue and 48.2 for pain for MM patients compared to scores of 25.0 and 16.9 for a general population. The results of the sensitivity analysis indicated that estimation of the SDs for those studies missing the statistic did not have a significant effect on the summary mean estimate. In most cases, the inclusion of additional means with estimated SDs reduced the summary SE estimate associated with the summary mean. Overall, the scores for fatigue and pain across research articles involving newly-diagnosed patients (fatigue=48.5 and pain=49.1) were statistically higher (indicating worse pain and fatigue) than among patients who were recurrent or receiving more aggressive treatments (fatigue=39.9 and pain=38.7). Conclusions: The burden of pain and fatigue in MM is substantial and is different between newly-diagnosed and more advanced MM patients. Pain and fatigue can be easily quantified using standardized health-related quality of life instruments. Pivotal clinical trials in MM need to assess the impact of novel treatments on pain and fatigue. Disclosures Trask: Sanofi: Employment. Atkinson:Sanofi: Research Funding. Trivedi:Sanofi: Research Funding. Palsgrove:Sanofi: Research Funding. Jones:Sanofi: Employment. McHorney:Sanofi: Research Funding.

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