scholarly journals Effect of High Intensity Chemotherapy Vs Targeted Therapy on Survival in AML Patients Aged 60-75

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4125-4125
Author(s):  
Kieran D Sahasrabudhe ◽  
Melanie T Rebechi ◽  
Ying Huang ◽  
Greg K. Behbehani ◽  
Bhavana Bhatnagar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Targeted Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Treatment Intensity ◽  
Intensive Chemotherapy ◽  
Blood Cell Count ◽  
Advisory Committees ◽  
Disease Characteristics

Abstract Introduction The FDA has recently approved several oral targeted therapies for Acute Myeloid Leukemia (AML). These therapies have been approved in patients with relapsed/refractory disease and as frontline therapy in patients ineligible for intensive induction chemotherapy. These agents are also being increasingly utilized as frontline therapy in patients of all ages and fitness levels on clinical trials and through off label prescribing. The decision to use intensive chemotherapy vs targeted therapy is particularly relevant in patients aged 60-75 due to the heterogeneous nature of this population with respect to disease characteristics, performance status, and comorbidities. However, the relative survival impact of intensive chemotherapy vs targeted therapy in this patient population has not been extensively studied. We conducted a retrospective analysis to compare survival outcomes of these treatment approaches and to determine the relative impact of treatment intensity compared to other variables that are known to affect survival in AML patients. Methods In this single-center, retrospective study, patients aged 60-75 diagnosed with AML from 2016-2020 were included if they received treatment with high intensity chemotherapy (HiC), low intensity targeted therapy (LITT), or both during the course of treatment and prior to transplant. HiC was defined as a regimen containing cytarabine + an anthracycline given on a "7+3" based schedule. Patients treated with liposomal cytarabine-daunorubicin were excluded. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or in combination with a hypomethylating agent. Between-group analysis was conducted for patients who had received HiC at any point during treatment (any HiC) vs patients who had not (LITT only). Overall Survival (OS) was analyzed by Kaplan-Meier method with log-rank test used for between-group comparisons. Cox regression model was used to associate risk factors with OS. Univariable models were first fit, then a multivariable model was built using backward selection. Transplant status was included as a time-dependent variable. Results A total of 141 patients were included, 80 received any HiC and 61 received LITT only. Compared with the any HiC group, patients in the LITT only group demonstrated older age, a higher percentage of secondary AML, a lower percentage of FLT3 ITD mutations, a higher percentage of IDH1 and IDH2 mutations, a lower white blood cell count, and a trend toward higher ELN risk classification at baseline (Table 1). Median OS was significantly longer in the any HiC group (21.8 months vs 13.6 months). A significantly higher percentage of patients receiving any HiC underwent allogeneic stem cell transplantation, but post-transplant OS was not significantly different between the two groups (Table 2). On univariable analysis, receipt of HiC, lower ELN risk classification, and receipt of transplant were all significantly associated with superior OS. Age, performance status, secondary AML, and white blood cell count at diagnosis notably did not have a significant association with OS in this cohort. On multivariable analysis, treatment intensity was no longer found to have an independently significant impact on survival after accounting for ELN risk (hazard ratio (HR) for unfavorable 3.02, p<0.01) and receipt of transplant (HR 0.25, p<0.01) (Table 3). Discussion The results of this study show that baseline disease characteristics and receipt of transplant were the most important predictors of survival in this cohort of AML patients aged 60-75. These factors were notably more impactful than treatment intensity and chronological age. These findings support the use of transplant in this patient population regardless of treatment intensity, especially in those with higher risk disease. Limiting factors in this study include the retrospective design and relatively small sample size. Ultimately, larger trials with more patients will be needed to confirm these findings including prospective, randomized trials comparing intensive chemotherapy to lower intensity targeted therapy in patients who are transplant-eligible at baseline. Figure 1 Figure 1. Disclosures Bhatnagar: Novartis: Honoraria; Pfizer: Honoraria; Kite: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Astellas: Honoraria; Cell Therapeutics: Honoraria, Research Funding. Blachly: INNATE: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; KITE: Consultancy, Honoraria. Borate: Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Mims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Vasu: Seattle Genetics: Other: travel support; Boehringer Ingelheim: Other: Travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Walker: Novartis: Other: clinical trial support; Geron: Other: clinical trial support; Newave: Other: clinical trial support.

scholarly journals Additional Cytotoxic Chemotherapy Is Unlikely to Eliminate Measurable Residual Acute Myeloid Leukemia (AML)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 260-260 ◽  
Author(s):  
Jacob Appelbaum ◽  
Anisha Loeb ◽  
Kelda Gardner ◽  
Carole M. Shaw ◽  
Paul C. Hendrie ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Cox Models ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Additional Chemotherapy

Background: Measurable residual disease (MRD) following intensive induction chemotherapy for AML is associated with a high risk of relapse and shortened survival even after allogeneic hematopoietic stem cell transplantation (HSCT). Thus, it may be advisable to give additional chemotherapy to reduce or eradicate MRD prior to HSCT. However, this may expose patients to additional toxicity and delay HSCT. We used our institutional database to examine how often additional chemotherapy eliminated MRD and compared survival among patients with MRD according to whether they next received additional chemotherapy or allogeneic HSCT. Methods: We reviewed 1272 remission induction attempts in 917 patients at our institution from 2008-2016. We identified 217 patients in CR/CRi with MRD (<5% abnormal blasts, assessed by multiparameter flow cytometry) generally after one course of therapy. Four patients were excluded due to ambiguous reporting or the presence of an additional concurrent hematologic neoplasm. Baseline clinical variables were used to calculate the treatment related mortality score, TRM (Walter et al. JCO 2011; 29(33):4417-4424). Comparisons used chi square tests for categorical and rank sum tests for continuous variables. Survival was evaluated using the Kaplan Meier method. Univariate Cox models found that performance status (HR 1.7, 95% CI 1.4-2.2) but not presentation WBC, cytogenetic risk, sex, or secondary AML were associated with significant hazard ratios. Kaplan-Meier analysis was used to examine the effect of treatment strategy on survival. Results: The median follow-up time was 31.1 months, the median survival following 1-2 cycles of remission induction was 11 months (95%CI 9.1 - 12.42). Next therapies were HSCT in 80 patients, additional chemotherapy in 49 patients (28 intensive; 10 less intensive, e.g. azacitidine; 11 novel agents) and none in 84 patients. In the patients who received additional chemotherapy, MRD was eliminated in 10/49 patients (20.4%, 95% CI 10.2 - 34.4%, CR = 7 pts, CRp = 3 pts): 0/21 following novel agents or low intensity therapy and 10/28 following intensive therapy (36%; 19-56%). Median survival from initial chemotherapy was similar regardless of whether MRD was eliminated by chemotherapy (12.4 mo) or was not (11.0 mo). Following chemotherapy, 16 patients were subsequently transplanted: 7 of 10 in CR/CRi and 9 with residual AML (6 patients with residual AML received intensive chemotherapy). Survival from the time of initial chemotherapy was longer in the 80 patients who received HSCT as first treatment for MRD than in the 49 who received chemotherapy (top figure panel, median 13.8 mo vs 11.6 mo, p = 0.01). and was not statistically different from the survival times of the 16/49 who received HSCT after chemotherapy for MRD, despite the "guarantee time" these 16 enjoyed. From the time of transplantation, survival was shorter among the 16/49 patients who received chemotherapy followed by transplant compared to those transplanted upfront (bottom figure panel median 4.4 vs. 10.4 mo, p = 0.02). There was no difference in survival after transplantation between patients whose MRD was eliminated (n = 7 pts) or not (n = 9) by chemotherapy. Among patients treated with HSCT up front, 23 of 80 (28.8%; 95%CI 19.1-40%) survived longer than 1 year. Univariate Cox models found that performance status at presentation (HR 1.7, 95% CI 1.4-2.2) but not presentation WBC, cytogenetic risk, sex, or secondary AML were associated with significant hazard ratios. Conclusion: Intensive chemotherapy eliminated MRD in only 36% of cases, whereas less intensive or novel therapy was unsuccessful in 21 consecutive cases. Whether preceding chemotherapy eliminated residual MRD had no effect on post-HCT outcome. There was a trend toward improved long-term survival in patients who were transplanted upfront rather than after additional chemotherapy. Overall, the use of additional chemotherapy to eliminate MRD prior to HCT does not seemingly improve HCT outcomes and appears less successful than proceeding directly to HCT. Absent a clinical trial, HCT may be the best treatment of people with MRD+ AML. Our data provide a historical response rate for such trials. Figure Disclosures Gardner: Abbvie: . Percival:Nohla Therapeutics: Research Funding; Pfizer Inc.: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Halpern:Bayer Pharmaceuticals: Research Funding; Pfizer Pharmaceuticals: Research Funding. Scott:Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Speakers Bureau. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy; NCCN: Consultancy. Walter:Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding; Amphivena Therapeutics: Consultancy, Equity Ownership; Agios: Consultancy; Amgen: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding. Becker:AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy; The France Foundation: Honoraria. Jensen:Juno Therapeutics, a Celgene Company: Research Funding; Bluebird Bio: Research Funding.

scholarly journals Clinical Utility of a Multi-Gene Next-Generation Sequencing Myeloid Panel in an Academic Hematology Practice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1408-1408
Author(s):  
Pedro G Vianna ◽  
Richard D. Press ◽  
Henning Stehr ◽  
Fei Yang ◽  
Linda Gojenola ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Board Of Directors ◽  
Research Funding ◽  
Pathogenic Variant ◽  
Advisory Committees ◽  
Management Guidance ◽  
Generation Sequencing

Background Next-generation sequencing (NGS) panels have created an unprecedented opportunity to interrogate a broad array of variants in a multiplex fashion. Few data have demonstrated how NGS testing impacts diagnosis and treatment decisions. In this retrospective analysis, we evaluated the clinical application of NGS myeloid panels (MP) in patients (pts) evaluated by physicians in the Stanford Division of Hematology. Methods The study was approved by the Stanford University IRB. The cohort consisted of 1,015 pts ≥18 years of age (median 66; range 18-96 years; 51% female). A total of 1,213 MPs obtained from peripheral blood (n=568) or bone marrow (n=645) from March 2017 to June 2018 were analyzed at Stanford (n=761) using the 54-gene TruSight® Myeloid Sequencing Panel (Illumina, San Diego, CA) or Oregon Health & Science University (n=452) using the GeneTrails® Hematologic Malignancies 76-Gene Panel. Electronic medical records were reviewed from t-3 to t+9 months from when MPs were obtained to assess physician reasoning for MP acquisition, documentation of results, and how results were clinically applied. We defined three categories of MP acquisition: 1) diagnostic clarification, 2) prognostication and/or management guidance, or 3) minimal residual disease (MRD) monitoring. We analyzed changes in clinical management, including addition of targeted or non-targeted therapeutics, clinical trial eligibility, or other practice recommendations. Results Of the 1,213 MPs, 882 (73%) demonstrated at least one pathogenic/ likely pathogenic variant (median 2; range 1-8). Median turn-around-time was 18 days (range 7-31) and average cost was $2,600. Of all MPs, 462 (38%) were obtained for diagnostic clarification, 732 (60%) for prognostication / management guidance in pts with known myeloid (n=701) or lymphoid (n=31) neoplasms, and 19 (2%) for MRD monitoring, although the assay was not designed for this indication. MPs were ordered to clarify a diagnosis for the following reasons: unexplained cytopenia(s) (n=199), molecular profiling for a suspected hematolymphoid neoplasm (n=156), unexplained -cytosis (n=86), and testing for other lab abnormalities (e.g. elevated serum tryptase, paraproteinemia) (n=18), or signs (e.g. splenomegaly, splenic vein thrombosis)(n=3). A pathogenic/likely pathogenic variant was found in 294 (64%) pts, confirming or establishing the presence of a myeloid (n=266) or lymphoid neoplasm (n=7) or resulting in a diagnosis of CHIP (n=9) or CCUS (n=12) in pts who did not meet 2016 World Health Organization diagnostic criteria for a hematolymphoid neoplasm (Fig. 1). Of the 732 MPs ordered for prognostication/ management guidance, 272 MPs (37%) were obtained in the initial workup of non-APL AML pts. The frequency of favorable (21%), intermediate (55%), and adverse risk (24%) genetics according to the European LeukemiaNet stratification in non-APL AML is shown in Figure 2a, which also denotes the frequency of favorable (9%) or adverse risk (70%) variants in MDS, and adverse risk variants in MF (52%), MDS/MPN (68%), and advanced systemic mastocytosis (44%). Among MPs obtained for prognostication/ management guidance, 163 (22%) led to a modification in clinical practice, divided between 132 (18%) which led the physician to change therapy (e.g. FDA-approved targeted therapy, clinical trial, or FDA-approved therapy, such as hypomethylating agents in MDS) and 31 (4%) resulted in a non-therapeutic change (e.g. expedited HSCT referral or more frequent follow-up)(Fig. 2b). 87 pts with a myeloid neoplasm had 184 repeat MPs for relapsed/refractory disease (n=52), transformation to higher-risk MDS or AML (n=45) or progressive cytopenias (n=87). Among these MPs, 38 (21%) identified a new pathogenic/likely pathogenic variant of which 29% (n=11) led to either a) initiation of targeted therapy with enasidenib in relapsed IDH2+ AML (n=3) or midostaurin for secondary FLT3+ AML from MDS (n=3), or b) consideration for a clinical trial with a splicing modulator for MDS characterized by a splicing variant (n=5). Conclusion In our academic hematology practice, two-thirds of MPs ordered for diagnostic clarification identified a pathogenic/likely pathogenetic variant that helped to confirm or establish a new diagnosis of a hematolymphoid neoplasm, CHIP, or CCUS. In addition, approximately 20% of MPs ordered for prognostication/ management guidance led to a change in clinical practice. Disclosures Gotlib: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicines: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Promedior: Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Allakos: Honoraria, Membership on an entity's Board of Directors or advisory committees; Deceiphera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Novel Cytokine-Mediated Mechanism of Action Identified By Quantitative Seroproteomics in Multiple Myeloma Patients Treated with Tagraxofusp, a Novel CD123-Directed Targeted Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1620-1620
Author(s):  
Arghya Ray ◽  
Clifton C. Mo ◽  
Ting DU ◽  
Arturo Olguin ◽  
Janice Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
New York ◽  
Multiple Myeloma ◽  
Targeted Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Phase 1 ◽  
Fold Change ◽  
Publicly Traded ◽  
Advisory Committees

Abstract Introduction Plasmacytoid dendritic cells (pDCs) express CD123/IL-3Rα and promote tumor growth and immunosuppression in multiple myeloma (MM) (Chauhan et al, Cancer Cell 2009, 16:309-323; Ray et al, Leukemia, 2018, 32:843-846). Tagraxofusp is a novel targeted therapy directed against CD123, and is FDA-approved for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm [BPDCN]). Tagraxofusp can also trigger anti-MM activity by reducing the viability of immunologically defective and tumor-promoting pDCs in MM. Furthermore, tagraxofusp synergistically enhances the anti-MM activity of anti-MM agents bortezomib and pomalidomide. Our preclinical findings led to a recently completed phase 1/2 clinical trial of tagraxofusp with pomalidomide/dexamethasone in relapsed/refractory MM patients (NCT02661022). Results demonstrated preliminary safety and efficacy, with 5 of 9 heavily pretreated patients achieving durable partial response (PR) (ASH 2019). Here, we report the early results of our translational correlative studies using bone marrow (BM), peripheral blood (PB), and serum from the study cohort. Methods Tagraxofusp is a bioengineered targeted therapy directed to CD123 comprised of human IL-3 fused to a truncated diphtheria toxin (DT) payload (Stemline Therapeutics, NY). pDCs and patient MM cells were purified from BM/PB samples after informed consent, and quantified using FACS, as described (Ray et al, Leukemia, 2018). A novel high throughput seroproteomics platform SOMAscan was used to analyze 1,310 protein analytes in serum samples from MM patients (n = 9). SOMAscan data were subjected to meta-analysis to generate heatmaps, followed by hierarchical cluster analysis. SOMAscan results were validated with ELISA using supernatants from MM patient pDCs cultured with or without tagraxofusp. Results Analysis of BM/PB samples from MM patients receiving tagraxofusp therapy showed a distinct reduction in the frequency of viable pDCs [average 2% at screening vs 0.75% post-tagraxofusp; n = 6; p = 0.036]. Of note, pDCs isolated from tagraxofusp-treated patients showed decreased ability to trigger MM cell growth. SOMAscan analysis of patient serum before and after tagraxofusp therapy showed alterations in the levels of 100 proteins [Median Fold Change in expression: 0.39 to 4.5; n = 6; 3 each; p < 0.05]. Importantly, tagraxofusp treatment reduced pDC-related soluble proteins including IFN-α (fold change: 0.8, treated vs untreated; p < 0.05). Pathway analysis further show that treatment affected immune signaling. For example, tagraxofusp decreased the levels of immunosuppressive proteins, soluble CD40L and IL1R2 (0.071-fold and 0.088 fold vs untreated; p = 0.02 and p = 0.013, respectively), promoting immune response. Moreover, analysis of end of treatment samples showed decreased soluble C-reactive protein, affecting the complement cascade after treatment (0.53-fold, p = 0.0173) via the downregulation of several C-C motif soluble chemokines (p < 0.05). Our earlier study showed that pDC-MM interactions triggered secretion of IL-3, which in turn promotes both pDC survival and MM cell growth. Importantly, tagraxofusp in this trial decreased serum IL-3 levels (fold change 0.75, treated vs untreated; p < 0.05). Conclusions In the present study, we validate the target specificity of tagraxofusp against MM pDCs in relapsed and refractory MM patients enrolled in a phase 1/2 clinical trial. A future clinical trial of tagraxofusp in combination with bortezomib and pomalidomide will examine the utility of tagraxofusp to improve outcome in patients with relapsed refractory MM. Disclosures Mo: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy. Olguin: Stemline Therapeutics, New York, NY: Current Employment. Chen: Stemline Therapeutics, New York, NY: Current Employment. Brooks: Stemline Therapeutics: Current Employment. Mughal: Stemline: Current Employment, Current holder of stock options in a privately-held company; Oxford University Press, Informa: Other: financial benefit and/or patents . Richardson: Janssen: Consultancy; Celgene/BMS: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding; AstraZeneca: Consultancy; Takeda: Consultancy, Research Funding; AbbVie: Consultancy; Protocol Intelligence: Consultancy; Regeneron: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Chauhan: Oncopeptides: Consultancy; C4 Therapeutics: Current equity holder in publicly-traded company; Stemline Therapeutics: Consultancy. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Analysis of Elderly Patients (≥70 years old) with Acute Leukemia in the Era of Targeted Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5100-5100
Author(s):  
Alon Rozental ◽  
Shai Shimony ◽  
Pia Raanani ◽  
Ofir Wolach
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Elderly Patients ◽  
Acute Leukemia ◽  
Board Of Directors ◽  
Intensive Therapy ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Entire Cohort

Background Analysis of SEER database shows that the median age of acute myeloid leukemia (AML) patients at diagnosis is 68 years, with ~1/3 of patients older than 75 years. Although acute lymphoblastic leukemia (ALL) is mainly a disease of the younger population, ~12% of patients are older than 65 years old at diagnosis. Elderly patients suffer from increased toxicity compared to younger patients translating into a need for reduction in chemotherapy dose intensity as well as a higher rate of early death. Elderly patients, 70 years of age and older, receiving intensive chemotherapy have an extremely poor outcome with reported median overall survival (OS) of approximately 4 months in ALL and 6-12 months in AML. Within the last couple of years a flurry of targeted therapies has been introduced into clinical practice and new treatment opportunities for older patients have become available. We sought to investigate the pattern of targeted therapy utilization and clinical trial enrollment in the older patients with acute leukemia in our center. Methods A single center retrospective analysis of patients aged ≥ 70 years with newly diagnosed acute leukemia treated at a the hemato-oncology admission unit in a large tertiary center between 4/2011 and 4/2019. Results 52 patients [AML (n=44 including 3 acute promyelocytic leukemia), ALL (n=5), mixed phenotype acute leukemia (n=2) and blastic plasmacytoid dendritic cell neoplasm (n=1)] were included in the analysis. 44% of the entire cohort received novel approaches with 26.9% of patients enrolled in clinical trials and 30.7% receiving targeted therapy in the off-trial setting (in all lines of therapies). Due to the small cohort of non-AML patients, we present herein in detail the results of the non-APL AML patients only (Table 1). Most of the AML patients had high-risk features such as therapy related AML (n=12), AML with myelodysplastic-related changes (n=9). Adverse risk cytogenetics was observed in 13 patients. 17 patients (41%) received intensive chemotherapy, mainly the "3+7" induction regimen with daunorubicin 60mg/m2/day. 58.6% were considered ineligible for intensive chemotherapy due to age and comorbidities, third of those patients were enrolled into clinical trials, and two-thirds received either Azacitidine alone, LDAC alone, or in combination with venetoclax. The most used targeted agent was venetoclax (combined with either azacytidine or LDAC) which was given to 12 patients (all lines of therapies) achieving 1-year OS of 50%. The complete remission (CR) rate for patients receiving intensive chemotherapy was 41% and the 1-year OS was 47.1% with a median OS of 10.3 months compared to 37.5% CR and a median OS of 3.7 months for patients receiving non-intensive therapy (95% CI, 1.4-6, p=0.072, Figure 1a). Patients who received either targeted therapy or were enrolled upfront into a clinical trial had a 1-year OS of 44.4%. Four patients, median age of 73.5 years (70.7-73.7 years), underwent hematopoietic stem-cell transplantation in first remission , receiving non-myeloablative conditioning, with median OS of 75% at 1 year of follow-up. In a subgroup analysis of octogenerians (≥ 80 years old), all 11 patients were diagnosed with AML, and 63% of them had either therapy-related AML or AML with myelodysplastic-related changes. All received non-intensive therapy with 36% receiving either targeted therapy or enrolled into a clinical trial. Interestingly, although the1-year OS of the octogenerians was 36%, those on a clinical trial or receiving targeted therapy had 1-year OS of 91%. For the entire cohort (including non-AML patients), patients who were either enrolled into a clinical trial or received targeted therapy had 1-year OS of 47.8% with a median OS of 10.3 months compared to 37.9% and median OS of 4.2 months 1-year OS for those who did not receive targeted therapy or were not enrolled into a clinical trial (95% CI, 1.8-18.8, p=0.618, Figure 1b). Conclusions Patients over 70 years of age with acute leukemia seem to benefit from the administration of targeted therapy and/or enrollment into clinical trials compared to standard approaches. This holds true also for octogenerians. If this is not feasible, a selected group of carefully chosen patients might benefit from intensive therapy as well. Disclosures Wolach: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker.

scholarly journals Prognostic Significance of Hospitalization Status at Second Cycle of Hypomethylating Agent Induction Therapy in Acute Myeloid Leukemia Patients Ineligible for Intensive Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5102-5102
Author(s):  
Douglas Tremblay ◽  
Rafael Madero-Marroquin ◽  
Guido Lancman ◽  
Alexander Coltoff ◽  
Jonathan Feld ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
De Novo ◽  
Performance Status ◽  
Intensive Chemotherapy ◽  
Therapeutic Approaches ◽  
Exclusion Criteria ◽  
Advisory Committees

Introduction: Hypomethylating agents (HMAs) are used as induction therapy for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. HMA therapy is frequently initiated in the hospital and some patients remain hospitalized through the initiation of cycle 2 (C2). Clinicians are often faced with the decision to administer C2 while the patient is still hospitalized, however, there is a paucity of prognostic information to guide treatment decisions in this common scenario. Methods: We conducted a retrospective review of patients diagnosed with treatment naïve, de novo and secondary AML who were ineligible for induction chemotherapy (at the discretion of the treating physician based on advanced age, comorbidities, or other reasons) at a single, tertiary, referral center. Patients were included if they received induction therapy with an HMA, including azacitidine and decitabine between 7/1/2008 and 7/1/2018. Exclusion criteria included receipt of intensive induction chemotherapy and inadequate electronic medical documentation. Patients were divided into four groups: patients who were discharged after completion of C1 and received C2 as an outpatient (discharged after C1), patients who received C1 and C2 during the same hospitalization (C1-C2 continuous hospitalization), those who received one total cycle (C1 only), and patients who received C1 as an outpatient (C1 outpatient). The groups were analyzed separately for the primary outcome of overall survival (OS), calculated by Kaplan Meier analysis. Results: Out of 105 patients identified who received an HMA, 100 patients were identified who met inclusion/exclusion criteria and their baseline characteristics are shown in Table 1. Most patients had de novo AML (39.0%), although 33.0% and 19.0% of patients had AML secondary to myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), respectively. Additionally, 8 patients (8.0%) had therapy related AML. The majority of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2 at induction. Patients who received C1 as an outpatient had a significantly better performance status than those who did not (p= 0.033) Decitabine was the most common HMA (57.0%) administered and was most often on 5-day schedule. Eight patients (8.0%) were continually hospitalized until C2, 5 because of active medical issues (most often fevers requiring intravenous antibiotics), 2 had physical debility precluding discharge home, and 1 was receiving intrathecal chemotherapy twice weekly for central nervous system involvement of AML. The median OS was 15.6 months (95% CI 2.66-28.6) in patients who received C1 outpatient, 10 months (95% CI 6.67-13.43) in patients discharged after C1, 4 months (95% CI 2.40-6.40) in the C1-C2 continuous hospitalization group, and 1 month (95% CI 0.61-1.30) in those who only received C1 as shown in Figure 1. Patients discharged after C1 had a significantly longer OS compared to the C1-C2 continuous hospitalization group (p=0.003). There was a trend (p=0.054) towards worse survival in patients who received C1 only compared to patients hospitalized continually from C1-C2. Conclusions: Continued hospitalization from C1 to C2 of HMA therapy led to an extremely poor median survival of 4 months in this cohort, compared to 10 months in patients who were able to be discharged after C1 and receive C2 as an outpatient. Patients who only received a single cycle of HMA did not have a significantly different survival as compared to patients who were continually hospitalized from C1 to C2. While this is a small retrospective series, these data suggest that AML patients still requiring hospitalization at time of C2 of HMA therapy should be re-evaluated for alternative therapeutic approaches including hospice given poorer outcomes. Although this grouping selects for patients who are sicker and unable to leave the hospital, there is apparent lack of significant benefit of continued HMA therapy in the majority of patients while inpatient. The impact on hospital length of stay, unnecessary utilization of healthcare resources, and patient's quality of life should also be considered in these cases. Prospective identification of these patients with a poorer prognosis could lead to better alternatives for therapeutic approaches. Disclosures Kremyanskaya: Incyte, Celgene, Constellation, Protagonist.: Research Funding; La Jolla: Consultancy. Navada:Onconova Therapeutics Inc: Research Funding. Mascarenhas:Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Promedior: Research Funding; Roche: Consultancy, Research Funding; Janssen: Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Unexpected Toxicities When Nivolumab Was Given after Allogeneic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1956-1956
Author(s):  
Amy Wang ◽  
Justin Kline ◽  
Wendy Stock ◽  
Satyajit Kosuri ◽  
Andrew S. Artz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Stem Cell ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Checkpoint Inhibitors ◽  
Advisory Committees ◽  
Relapsed Disease

Background:Treatment options are limited for patients (pts) with hematologic malignancies who relapse after allogeneic stem cell transplantation (allo-SCT). We hypothesized that checkpoint inhibitors may offer a novel approach for maintaining remission after allo-SCT. Data from pre-clinical studies have suggested a potential role for PD-1/PD-L1 inhibitors in acute myeloid leukemia (AML) (Zhang et al., Blood 2009), so it is possible that immunomodulation with checkpoint inhibitors could stimulate the donor anti-leukemia immune response and prevent disease relapse. However, the safety of checkpoint blockade early after allografting remains to be established. Methods:We conducted a pilot study to assess the tolerability and efficacy of Nivolumab, a PD-1 inhibitor, as maintenance therapy after allo-SCT (NCT02985554). Pts were eligible if they were post allo-SCT without evidence of relapse or active graft-vs-host disease (GVHD) or history of prior greater than stage I skin acute GVHD. Nivolumab was to be administered intravenously at 1mg/kg every 2 weeks for 4 doses followed by dosing every 12 weeks. Treatment started 4 weeks after routine immunosuppression was discontinued until 2 years after the transplant. The primary objective was to determine the tolerability of Nivolumab on this schedule. Secondary objectives were evaluation of adverse events, relapse, and overall survival. Results:Four pts were enrolled from December 2017 through November 2018. (Table 1)All pts experienced immune-related adverse events (irAE) from Nivolumab, and 2 (50%) pts experienced serious adverse events. (Table 2)One pt developed grade (G) 4 neutropenia soon after the first dose. (Figure 1)The absolute neutrophil count nadired at 20 cells/µL, at which point pegfilgrastim was administered. An interim bone marrow biopsy (BMBx) confirmed no evidence of relapsed disease. Full neutrophil recovery occurred approximately 3 months after the initial dose, and no subsequent toxicities occurred. Another pt developed G3 autoimmune encephalopathy concurrently with G2 transaminitis and G2 thrombocytopenia after one dose of Nivolumab. (Figure 2)Intravenous methylprednisolone (1mg/kg daily for 3 days) and immunoglobulin (2g/kg in 4 divided doses) were administered, followed by a 7-week steroid taper with full resolution of symptoms. Relapsed disease was ruled out by a BMBx. A third pt developed G2 skin rash approximately 10 days after the first dose of Nivolumab. Skin biopsy demonstrated drug hypersensitivity reaction vs GVHD, and the pt was treated with a 3-week prednisone course (starting at 1mg/kg followed by a taper). A mild flare recurred 2 weeks later, which was treated with topical steroids only. However, Nivolumab was not resumed. The fourth pt developed G2 elevated TSH approximately 2 months into therapy and after 4 doses of Nivolumab. Thyroid hormone replacement was initiated with subsequent symptom improvement and normalization of TSH over a 4-month period. As a result of these unexpected severe toxicities, the study was closed to further enrollment, and further Nivolumab administration ceased. Thus far, one pt (#1) relapsed after a total remission duration of 530 days; the remission duration after starting Nivolumab was 318 days. One pt has mild chronic skin GVHD. All 4 patients remain alive with a median overall survival of 2.3 years (range, 1.9-4.7). Conclusions:Even at low doses, the use of Nivolumab as maintenance therapy in the post allo-SCT setting was not tolerable at the current dosing and schedule due to an unexpected number of high grade irAEs. Additional studies of dose and timing after allo-SCT are needed to improve safety and tolerability, in conjunction with correlative studies to better understand the immunomodulatory processes in the post-transplant setting. Disclosures Kline: Merck: Honoraria; Merck: Research Funding. Stock:Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Research to Practice: Honoraria. Artz:Miltenyi: Research Funding. Larson:Agios: Consultancy; Novartis: Honoraria, Other: Contracts for clinical trials; Celgene: Consultancy. Riedell:Novartis: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau. Bishop:CRISPR Therapeutics: 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, Research Funding; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Liu:Arog: Other: PI of clinical trial; BMS: Research Funding; Agios: Honoraria; Novartis: Other: PI of clinical trial; Karyopharm: Research Funding. OffLabel Disclosure: Nivolumab used as maintenance therapy in the post-transplant setting

The Characteristics, Treatment Patterns, and Outcomes of Older Adults with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4463-4463
Author(s):  
Mark A. Fiala ◽  
Tanya M. Wildes ◽  
Mark A. Schroeder ◽  
Armin Ghobadi ◽  
Keith E. Stockerl-Goldstein ◽  
...  
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Advisory Committees ◽  
Improved Outcomes ◽  
Immunomodulatory Drug

Abstract Background: Advances in the treatment for multiple myeloma (MM) have dramatically improved outcomes for younger patients. Older adults, particularly those 80 years of age or older at diagnosis, have seen more modest gains. MM incidence increases with age, and as more of the population is living later into life, the segment of the MM population over 80 will continue to grow. In this study, we sought to better understand the characteristics, treatment, and outcomes of older patients with MM. Methods: We identified all patients diagnosed with MM at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2007-2013 to determine incidence and outcomes. Subset analysis was then performed on patients included in the SEER-Medicare linked database who were enrolled in Medicare Parts A, B, and D to further explore patient characteristics and treatment patterns. Results: The incidence of MM increases over age, peaking after age 80. The annual incidence for those aged 65-69, 70-74, 75-79, 80-84 and 85+ was 24.4, 32.7, 39.5, 42.8 and 36.4 per 100,000, respectively. Based on 2010 US population estimates, approximately 4,500 new cases of MM were diagnosed annually 2007-2013 in patients age 80 or older. In that period, 8,093 cases, approximately 1,150 per year, were reported to SEER. The estimated median overall survival (OS) of these patients was 14 months (95% CI 13.2-14.8). The estimated relative 12 month survival was 58.9% (95% CI 57.4-60.4) compared to their peers without cancer. Of the 8,093 cases of MM reported to SEER during the study period, 2,385 were present in the SEER-Medicare linked dataset. Of these, 225 were identified as smoldering MM using a previously established algorithm (Fiala, et al, JCOCCI, 2018) and excluded leaving 2,160 for the analyses. The median age was 84 (range 80-100) and 55% were female. 81% were white, 13% black or African-American, and 6% another race. At disease presentation, 22% had claims indicating hypercalcemia, 61% renal failure or chronic kidney disease, 59% anemia, and 34% MM bone involvement. The estimated median OS was 13.4 months (95% CI 12.2-15.1). Only 52% of patients had claims indicating they received systemic MM treatment within 6 months post-diagnosis. Nearly all that did received novel agents; 38% received bortezomib-based treatment, 41% immunomodulatory drug (IMID)-based, and 14% both. The others received antineoplastic chemotherapies such as melphalan or cyclophosphamide. Interestingly, bortezomib utilization increased incrementally from 25% of patients treated in 2007 to 62% in 2013 while IMID utilization declined from 67% to 49%. The median OS of those receiving treatment was 21 months (95% CI 18.5-23.1) compared to 6.3 months (95% CI 5.3-7.3) for those who did not (p <0.0001). MM treatment was associated with a 26% decrease in hazard for death (aHR 0.74; 95% CI 0.67-0.82; p < 0.0001) independent of age, race, gender, poverty, comorbidities, and proxy measures of performance status. Outcomes improved for patients in more recent years; the hazard for death decreased by 3% (HR 0.97; 95% CI 0.94-0.99; p = 0.0096) each year 2007-2013. This can be attributed to increasing treatment rates. In 2007, only 41% of patients received treatment compared to 61% in 2013. After controlling for MM treatment, the year of diagnosis was no longer a significant predictor of survival. Conclusions: The outcomes of patients with MM over 80 years old are still relatively poor; nearly half of the patients do not receive systemic treatment and for those who do the median OS is just 21 months. The population over 80, when MM incidence peaks, is projected to triple over the next few decades. It is imperative that we improve our understanding of the needs of this vulnerable subgroup of patients of MM. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

The Tolerability of Combination Therapy with Thalidomide and 5-Azacitidine in Patients with Advanced Myelodysplastic Syndromes (MDS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1749-1749 ◽  
Author(s):  
Melita K Kenealy ◽  
John F Seymour ◽  
Cowan Linda ◽  
Alvin Milner ◽  
Pratyush Giri ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Respiratory Disorder ◽  
Advisory Committees ◽  
Impaired Performance

Abstract Abstract 1749 Poster Board I-775 Introduction Both thalidomide (Thal) and 5-azacitidine (Vidaza; AZA) have single-agent activity in patients (pts) with myelodysplastic syndromes (MDS), but there is limited experience with the combination. The addition of Thal to AZA may improve efficacy, but tolerability of the combination may be limited by side-effects. Patients and Methods This analysis included all evaluable pts on the Ph I/II Australasian Leukaemia and Lymphoma group (ALLG) MDS3 study of Thal and AZA. Pts were eligible if they had any FAB subtype of MDS; those with RA and RARS also required clinically significant cytopenias. Pts were excluded if they had previously received Thal or its derivatives or any demethylating agent. All pts were treated with Thal 50mg/d for the first 28d increasing to 100mg/d for a max of 12 Mo treatment and AZA 75mg/m2/d x7d every 28d until progression or prohibitive toxicity. The protocol specified dose delays or reductions for treatment-related toxicities. Results A total of 80 pts have been enrolled, with 41 treated between 7/08 – 7/09 currently evaluable. Median age is 68.5y (42-81) with 66% male. FAB MDS category was RA 15%, RARS 10%, RAEB 46%, RAEB-t 10% and CMML 17% with IPSS low 12%, intermed-1 37%, intermed-2 34% and high 12%. Median baseline Hb 88g/L (71-127), ANC 1.91×10 9/L (0.06-87.65) and platelets 75 ×10 9/L (10-399). Median time post diagnosis was 9 Mo. Seventeen pts (41%) remain on treatment with AZA alone (n=3) or both agents (n=14) with a median follow-up of 208d (60-297d). For those still on Thal and AZA median exposure to Thal is 209d (60-297d), with a median 7 cycles of AZA (2-9). For those 27 ceased Thal median exposure was 49d (17-220d) and of 24 ceasing AZA, median number cycles was 2 (1-8). Of 27 pts ceasing one (n=3) or both (n=24) agents; 7 withdrew consent, 3 at investigator decision, 4 for toxicity, 6 progressive disease, 1 lack of efficacy, 2 death (1 respiratory failure in setting of PD and WCC>300, 1 sepsis) and 4 unknown. There were 3 additional deaths within 28d of ceasing study therapy (all with PD); 2 due to sepsis and 1 intracranial haemorrhage. No pt experienced peripheral neuropathy Gr3 or worse. During cycle 1 of the first 40 consecutive patients on treatment, there were 18 episodes of Gr3+ non-haematologic toxicity in 13 patients; this was more likely in those with ECOG 2 (67% v 26%, p=0.053), age>65y (39% v 19%, p=0.175) and baseline ANC'0.5 (75% v 21%, p=0.008). Most of these events were infection related (a recognised risk of underlying MDS and of AZA alone); others occurred on only one occasion each (syncope, postop hemorrhage, respiratory disorder, renal failure, abdominal pain, pain, thrombosis and hypokalemia). Conclusions The combination of Thal 50-100mg/d and standard dose AZA is feasible without unexpected toxicity. Infections are common in the first cycle, particularly in pts with baseline neutropenia or impaired performance status. An updated toxicity analysis will be presented. Disclosures Kenealy: Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Seymour:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mills:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Szer:Celgene Pty Ltd: Honoraria, Speakers Bureau.

Variation in Health-Related Quality of Life by ECOG Performance Status and Fatigue Among Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4591-4591 ◽  
Author(s):  
Chris L. Pashos ◽  
Christopher R Flowers ◽  
Mark Weiss ◽  
Nicole Lamanna ◽  
Charles M Farber ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Clinical Practices ◽  
Employment Equity ◽  
Ecog Performance Status ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Ecog Ps ◽  
The Impact

Abstract Abstract 4591 Introduction: Clinicians and investigators appreciate the value of measuring HRQOL for monitoring CLL and the impact of treatments, and commonly use ECOG performance status (PS) and clinician-reported patient fatigue as surrogates for HRQOL in clinical practice. However, limited data exist on the relationships between PS, fatigue, and HRQOL in CLL patients (pts) undergoing treatment in clinical practices. We examined the associations between these measures and 3 psychometrically validated, patient-reported, HRQOL instruments: the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Methods: Data were collected as part of Connect CLL®, a prospective observational registry initiated in March 2010 involving US practices. Data on pt demographics and clinical characteristics were provided by clinicians. HRQOL was self-reported by pts at enrollment using the BFI, EQ-5D, and FACT-Leu. Mean BFI, EQ-5D and FACT-Leu scores were analyzed by ECOG PS and clinician-reported fatigue. Differences in HRQOL scores between sub-cohorts were assessed by ANOVA. Results: HRQOL data were reported by 604 pts enrolled from 10 academic, 148 community, and 3 government centers. Pts were predominantly male (62%) and white (90%); mean age was 70 (standard deviation 11) years. BFI data (scale: 0 [no fatigue] - 10 [worst fatigue]) indicated that on average pts report that global fatigue, fatigue severity and fatigue-related interference worsen by ECOG severity (Table 1) and are statistically associated with clinician-reported fatigue (Table 2). Mean EQ-5D overall HRQOL as measured by a Visual Analogue Scale (VAS) from 0 (worst) to 100 (best) worsens by ECOG severity and is significantly worse in pts with fatigue. Mean EQ-5D domain scores (scale: 1 [no problem], 2 [some problems], 3 [incapacity]) indicated that pain/discomfort, mobility and usual activities increase in severity as ECOG worsens and in pts with fatigue. FACT-Leu domains except social/family were statistically worse with worse ECOG PS and in pts with fatigue. Conclusions: Initial results from Connect CLL® indicate that HRQOL worsens with worsening ECOG PS, especially in physical / functioning domains, pain/discomfort, and mobility, and worsens across multiple domains among pts whose physicians reported fatigue. Future analyses should be conducted on how HRQOL, PS and fatigue may change over time with changes in CLL, and how they are influenced by therapies. These results may serve as baseline reference. Disclosures: Pashos: Celgene: Membership on an entity's Board of Directors or advisory committees. Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Weiss:Celgene: Membership on an entity's Board of Directors or advisory committees. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees. Farber:Celgene: Membership on an entity's Board of Directors or advisory committees. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Consultancy, Research Funding; Amgen: Research Funding. Lerner:Celgene: Membership on an entity's Board of Directors or advisory committees. Kay:Celgene: Membership on an entity's Board of Directors or advisory committees. Sharman:Celgene: Membership on an entity's Board of Directors or advisory committees. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees. Flinn:Celgene: Membership on an entity's Board of Directors or advisory committees. Kozloff:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Kahn:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Keating:Celgene: Membership on an entity's Board of Directors or advisory committees.

Long Term Treatment and Prevention Of Recurrent VTE In Cancer Patients: Results Of The Canadian Proact Survey

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5581-5581
Author(s):  
Normand Blais ◽  
Charles A. Butts ◽  
Mark A. Crowther ◽  
Nanette Cox-Kennett ◽  
Josée Martineau
Keyword(s):  
Clinical Trial ◽  
Board Of Directors ◽  
Research Funding ◽  
Term Treatment ◽  
Advisory Committees ◽  
Extended Treatment ◽  
Treatment And Prevention ◽  
Long Term Treatment ◽  
Recurrent Vte

Abstract Introduction Cancer associated thrombosis (CAT) is the second leading cause of death in cancer patients after death from cancer. Despite multiple available guidelines for CAT management, there remains variability in treatment practices. In order to gain insight on this variability in Canada, a survey was conducted to identify the perceived importance of managing CAT, identify differences in the pharmacological management of CAT, highlight the main barriers to optimal extended treatment and prevention of recurrent venous thromboembolism (VTE), outline challenges associated with long term treatment adherence, and identify predictors of patient non-adherence. Methods A survey was designed targeting physicians involved in the management of CAT. The questionnaire included queries on physician practice, 37 items related to beliefs and attitudes about extended treatment for prevention of recurrence of VTE, and a 30-item patient-specific profile. Results Responses were obtained from 21 professionals from four Canadian provinces (Nova Scotia, Quebec, Ontario, and Alberta); 76% were hematologists and/or oncologists, 14% were internists and 10% were pharmacists. Community and academic centers were well represented. Specific management profiles were obtained for 131 patients. Most care givers felt that VTE recurrence was an important issue deserving extended therapy for most patients. Although more than 90% believed bleeding and recurrent VTE risk should influence the length of treatment, only 62% believe that VTE recurrence risk should modify the type of treatment and 52% were concerned of the risk of bleeding with long term therapy (≥6 months). 71% of respondents believed patients’ lack of awareness of the risk of recurrent VTE reduces adherence to anticoagulant therapy for extended treatment of VTE. Although 100% of respondents detailed giving verbal patient counseling, only 19% provided written information to patients. 95% stated they assessed compliance verbally; less than 20% used more objective measures (pharmacy records, laboratory monitoring). Participants admitted to using results of clinical trials (95%) more than clinical guidelines (48%) as most felt that the published guidelines contained conflicting recommendations. The main drivers of treatment choice were clinical evidence, efficacy, and personal experience. No respondents indicated they preferred to use oral anticoagulants for extended therapy of CAT and 43% believed that LMWHs should not be used interchangeably. Most (95%) stated they follow-up with patients directly to reassess therapy after 3-6 months of treatment. The patient profile information showed the median age of patients was 62 years and 60% were female. Lung cancer, colon cancer, breast cancer, and lymphoma were the most common tumor sites and accounted for 50% of described cases. Cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) were evenly represented and 82% were symptomatic. Most events were temporally related to cancer therapy (69%), presence of a central venous catheter (18%), and recent surgery (17%). Less than 5% of these cases presented with a contraindication to anticoagulation therapy (severe thrombocytopenia, active bleeding) at CAT diagnosis. Most patients were treated in the outpatient setting. Nonetheless, hospitalization was required in 33% of cases with an average patient stay of 10.8 days. Hospitalized patients were preferentially treated with LMWH (84%) and usually stayed on the same regimen upon discharge (8.3 ± 6.4 months). Long term treatment was largely managed with LMWHs (most frequently dalteparin – 80% of all treated patients) while few were managed with vitamin K antagonists (6%) or novel direct antithrombotics (2%). Anticoagulant therapy for outpatients was prescribed for 9.0 ± 7.7 months after the most recent VTE episode. Conclusion In Canada, CAT is believed to be an important complication of cancer. Extended therapy is indicated for most patients with CAT.  Although bleeding risk is perceived as an important reason to modify therapy, contraindications to LMWHs were rare in the reported cases. Uptake of outpatient therapy of CAT is widespread in this country, yet hospitalization is still frequently required at diagnosis and is associated with prolonged inpatient stays. Even if non-adherence to antithrombotic therapy was believed to be rare among patients with CAT, this was rarely rigorously monitored. Disclosures: Blais: Pfizer: Consultancy; Sanofi: Consultancy; Leo: Consultancy. Butts:Pfizer: Consultancy, Honoraria, Speakers Bureau. Crowther:Pfizer: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees. Cox-Kennett:Pfizer: honorarium as a speaker Other. Martineau:Pfizer: honorarium as a speaker Other; Boehringer: honorarium as a speaker, honorarium as a speaker Other; Bayer: honorarium as a speaker, honorarium as a speaker Other; Sanofi: honorarium as a speaker and participated in clinical trial, honorarium as a speaker and participated in clinical trial Other; BMS: honorarium as a speaker Other.

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