Prevalence of Comorbidities Relevant to the Choice of Second-Generation (2-G) Tyrosine Kinase Inhibitor (TKI) for the Treatment of Chronic Myeloid Leukemia (CML) in the United States Using Real-World Claims Databases

Abstract Introduction: NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia recommend taking certain comorbidities into consideration when selecting a 2-G TKI. Based on toxicity profiles, dasatinib or bosutinib is preferred for patients (pts) with heart disease, arrhythmias, pancreatitis, and/or hyperglycemia; nilotinib or bosutinib is preferred for pts with a history of lung disease and/or who are at risk for pleural effusion. The prevalence of these relevant comorbidities in pts with CML was reported to be high in the US managed care setting, particularly in pts aged ≥ 65 years (Jabbour et al. CLML 2015), supporting the NCCN Guidelines® recommendations. To better understand the patterns of 2-G TKI selection in the first-line setting, this study was designed to assess the prevalence of relevant comorbid conditions in pts newly diagnosed with CML and treated with dasatinib or nilotinib using US real-world databases. Methods: Data for pts diagnosed with CML between 4/1/2013 and 3/31/2016 were extracted from the Truven Health Analytics Commercial and Medicare MarketScan Research databases, and data for pts diagnosed with CML between 4/1/2013 and 12/31/2016 were extracted from the Clinformatics Commercial and Medicare Claims databases. Eligible pts were adults treated with a TKI (imatinib, dasatinib, nilotinib) within 6 months after initial CML diagnosis who had continuous enrollment data for 6 months prior to CML diagnosis and 12 months after TKI initiation. The first TKI prescription was defined as the index date. Comorbidities of interest as stated in the NCCN Guidelines® (heart disease, arrhythmia, diabetes, pancreatitis, lung disease, and pleural effusion) were assessed within 6 months before initiation of a TKI. Results: A total of 649 pts and 471 pts were identified from the MarketScan and Clinformatics databases, respectively. Within these totals, 118 pts were identified from the MarketScan Medicare database, and 223 pts were identified from the Clinformatics Medicare database. The median age of pts from MarketScan was 55 years (dasatinib and nilotinib: 54 years), with 83% aged < 65 years (dasatinib: 86%; nilotinib: 85%). The median age of pts from Clinformatics was 63 years (dasatinib: 64 years; nilotinib: 62 years), with 54% aged < 65 years (dasatinib: 53%; nilotinib: 62%). Men comprised 57% (dasatinib: 58%; nilotinib: 55%) and 55% (dasatinib: 51%; nilotinib: 59%) of the population from MarketScan and Clinformatics, respectively. Forty-four percent of pts from MarketScan and 57% of pts from Clinformatics had at least 1 comorbidity of interest, as classified by the National Comprehensive Cancer Network® (NCCN®) (Table). For pts identified from the Medicare databases (typically aged > 65 years), 69% from MarketScan and 74% from Clinformatics had at least 1 comorbidity of interest. In the overall MarketScan and Clinformatics databases, respectively, 18% and 24% of pts with at least 1 instance of lung disease and/or pleural effusion were prescribed dasatinib, and 36% and 52% of pts with at least 1 instance of heart disease, arrhythmia, diabetes, and/or pancreatitis were prescribed nilotinib. In the MarketScan and Clinformatics Medicare databases, respectively, 18% and 33% of pts with at least 1 instance of lung disease and/or pleural effusion were prescribed dasatinib, and 61% and 70% of pts with at least 1 instance of heart disease, arrhythmia, diabetes, and/or pancreatitis were prescribed nilotinib. A relatively high proportion of pts treated with nilotinib had relevant comorbidities present at the time of treatment choice. Conclusions: In this large retrospective analysis using 2 US claims databases, up to 57% of pts had comorbidities relevant to the treatment of CML with TKIs. Despite this high incidence of comorbidities and the recommendations in the NCCN Guidelines®, a significant proportion of pts were prescribed a 2-G TKI with a side-effect profile that could exacerbate preexisting comorbid conditions. These data suggest that physicians may not be consistently considering comorbidities when choosing a first-line 2-G TKI for the treatment of pts with CML in the real-world setting. This study did not review the impact of dose adjustments due to relevant comorbidities per the NCCN Guidelines®. To ensure optimal care of pts with CML, increased awareness of the importance of comorbidities when selecting a TKI is needed. Disclosures Jabbour: Novartis: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Abbvie: Research Funding. You:Bristol-Myers Squibb: Employment. Le:Bristol-Myers Squibb: Employment. Brokars:Bristol-Myers Squibb: Employment. Brun:Bristol-Myers Squibb: Employment. Makenbaeva:Bristol-Myers Squibb: Employment.

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Adherence to Chronic Myeloid Leukemia Monitoring and Treatment Guidelines in Canadian Registries

Blood ◽

10.1182/blood.v128.22.3079.3079 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3079-3079

Author(s):

Christopher M Hillis ◽

Lambert Busque ◽

Julie Stakiw ◽

Donna L. Forrest

Keyword(s):

Chronic Myeloid Leukemia ◽

Data Collection ◽

Real World ◽

Myeloid Leukemia ◽

Research Funding ◽

Treatment Guidelines ◽

Imatinib Therapy ◽

Molecular Monitoring ◽

First Line ◽

Time Period

Abstract Background: Registry data in chronic myeloid leukemia (CML) complement clinical trial data, and can help determine how closely real world clinical practice adheres to guidelines. Several reports addressing this issue have suggested adherence to monitoring guidelines varies. However, no Canadian data on this topic has been published to date. To provide insight into this issue, we present data from the British Columbia (BC), Saskatchewan (SK), Ontario (ON) and Quebec (QC) CML registries. Methods: Data on cytogenetic and molecular monitoring were analyzed for CML patients treated with first-line imatinib from 2001-2015 in the BC registry, 2009-2014 in the SK registry and 2001-2014 in the ON registry. From 2006, clinicians in BC and SK were advised to follow the European LeukemiaNet (ELN) monitoring recommendations. Molecular monitoring of BCR-ABL for these provinces was conducted at the BC Cancer Agency Molecular Genetics Laboratory according to standard practices. In ON, clinicians were not advised to follow any particular guidelines and molecular and cytogenetic tests were conducted by the Hamilton Regional Laboratory Medicine Program using contemporary standards. In QC, province-specific guidelines were in place beginning in 2012 (see www.gqr-lmc-nmp.ca for specific guidance). Treatment patterns for patients treated with first-line imatinib from BC, SK and QC were analyzed for the 2001-2015, 2001-2014 and 2002-2012 time periods, respectively. Results: Monitoring data were collected for 234, 58 and 104 patients from BC, SK and ON, respectively. As shown in table 1, adherence to monitoring recommendations in Canada was 70% to 80% at 12 months. Treatment data were available for 234 BC patients, 73 SK patients, and 223 QC patients. Data on adherence to treatment recommendations were available for 58 SK patients diagnosed with CML and treated with first-line imatinib between 2009 and 2014. Of these 58 patients, over a quarter (n=15) experienced treatment failure or failed to meet ELN milestones without a change in therapy. Smaller proportions of patients receiving first-line imatinib therapy in BC and QC remained on imatinib therapy (see table 2). Discussion and Conclusions: These data suggest there is room for improvement with regards to adherence to CML monitoring and treatment recommendations in Canada. However, assessment of adherence to recommendations and inter-provincial comparisons are limited by the fact that monitoring and treatment guidelines have evolved over the data collection time period, as well as by differences in data collection strategies. For instance, in the ON registry, monitoring at the 3-month time point may be lower as testing was not typically conducted at 3 months in ON during the early 2000s. The opposite pattern observed in BC (with higher testing rates at 3 months dropping off by 18 months) may be attributable to the strict time period definition, with more patients receiving testing outside of the 4-week window after 1 year or more on treatment. In spite of these limitations, data collection through these registries continues to improve our understanding of real world CML populations and its management in Canada, as well as to spur initiatives aimed at improving CML care. This study was sponsored by Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by MedPlan Communications Inc. and was funded by Bristol-Myers Squibb. Disclosures Hillis: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria; Celgene: Consultancy. Busque:Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Stakiw:Roche: Research Funding; BMS: Honoraria; Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Jansen: Honoraria, Speakers Bureau. Forrest:BMS: Consultancy, Research Funding; Ariad: Honoraria, Speakers Bureau.

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Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2019-131114 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5571-5571

Author(s):

Jesus D Gonzalez-Lugo ◽

Ana Acuna-Villaorduna ◽

Joshua Heisler ◽

Niyati Goradia ◽

Daniel Cole ◽

...

Keyword(s):

Side Effects ◽

Real World ◽

Research Funding ◽

Treatment Patterns ◽

Line Treatment ◽

Event Free Survival ◽

First Line ◽

Treatment Change ◽

Free Survival ◽

First Line Treatment

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

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Specific Drug Transporter Genotypes Are Significantly Associated with Increased Rates of Major and Complete Molecular Responses In Newly Diagnosed Chronic Myeloid Leukemia Patients Treated with Imatinib – A TOPS Correlative Substudy

Blood ◽

10.1182/blood.v116.21.670.670 ◽

2010 ◽

Vol 116 (21) ◽

pp. 670-670

Author(s):

Simona Soverini ◽

Sabrina Angelini ◽

Eleonora Turrini ◽

Matt Burnett ◽

Gloria Ravegnini ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

Research Funding ◽

Phase Iii ◽

Molecular Response ◽

Newly Diagnosed ◽

First Line ◽

Favorable Alleles ◽

Summary Measures

Abstract Abstract 670 The availability of multiple options for chronic myeloid leukemia (CML) treatment is not paralleled by the availability of biological predictors of outcome allowing to identify patients (pts) who are more likely to benefit from dasatinib or nilotinib rather than imatinib (IM). Pharmacogenetics has proven a potential source of biomarkers given the known influence of polymorphisms in key genes encoding drug transporters and metabolizing enzymes on drug delivery – hence effectiveness. In CML, only two studies had so far explored this field, but both were conducted in heterogeneous populations including pts at different stages of disease, not all receiving IM first-line. We thus aimed to investigate a panel of 20 single nucleotide polymorphisms (SNPs) in ABCB1, ABCG2, SLC22A1, OATP1A2, OCTN1, CYP3A4 and CYP3A5 genes that can be hypothesized to influence IM transport and metabolism in 189 newly diagnosed CML pts enrolled in the TOPS phase III trial (Cortes et al, J Clin Oncol 2010). Pts selection was exclusively based on availability of written informed consent and sufficient amount of archived material. Median age was 46 years; male to female ratio was 103 to 86; 156 (83%) pts were Caucasian and 23 (12%) were Asian; low, intermediate and high Sokal risk pts were 84 (44.4%), 65 (34.4%) and 40 (21.2%), respectively. Baseline demographic/clinical features did not differ significantly from those of the overall population. Treatment outcomes (complete cytogenetic response [CCyR]; major molecular response [MMR] and complete molecular response [CMR]) were compared according to i) each candidate genotype ii) summary measures based on combinations of SNPs in the same gene and iii) summary measures based on combinations of SNPs in functionally related genes (uptake; efflux). CC genotype in OCTN1 had a favorable impact on the achievement of MMR at 12 months (MMR@12m; P = 0.03). With respect to the summary measures, combination of SNPs in the SLC22A1 gene was significantly correlated with MMR@12m (P = 0.03). When considering summary measures of uptake and efflux, the former was found to be associated with both MMR@12m and CMR@12m (P = 0.003 and P = 0.01, respectively). A separate analysis limited to Caucasian pts (n=156) yielded similar results (Table 1). In addition, the analysis in the Caucasian subgroup evidenced a significant association between the CC genotype in ABCB1 rs60023214 and MMR@12m (P = 0.005) (Table 1). Cumulative incidence plots based on the Kaplan-Meier method were also analyzed in the overall population and in Caucasians, with comparable results. Representative plots are shown in Figure 1. There was evidence for difference among MMR cumulative incidence curves for 2 single SNPs and 2 score measures. Presence of the major allele in OCTN1 (CC) and of the minor allele in CYP3A4 rs2740574 (GG) were associated with increased MMR rate (P = 0.028 and P = 0.042, respectively, in the overall population and P = 0.027 and P = 0.038, respectively, in Caucasians). Similarly, an increase in the number of favorable alleles in the SLC22A1 gene was associated with increased MMR rate (P = 0.030 and P = 0.043 in the overall population and in Caucasians, respectively). In addition, the combination of favorable alleles in the genes involved in IM uptake was associated with increased rates of both MMR and CMR (P = 0.004 and P = 0.015, respectively, in the overall population and P = 0.005 and P = 0.009, respectively, in Caucasians). Our results suggest that SNP genotyping might be helpful in selecting pts who are more likely to benefit from first-line use of more potent inhibitors. Further assessment of the SNPs here identified in larger series of pts is warranted. Supported by Novartis Oncology, Clinical Development, TOPS Correlative Studies Network Disclosures: Hughes: Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Research Funding; Ariad: Honoraria. White:Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Saglio:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Rosti:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Hatfield:Novartis: Employment. Martinelli:Novartis: Consultancy, Honoraria; BMS: Honoraria; Pfizer: Consultancy.

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Bosutinib As Therapy for Chronic Phase Chronic Myeloid Leukemia Following Failure with Imatinib Plus Dasatinib and/or Nilotinib: 24-Month Minimum Follow-up Update

Blood ◽

10.1182/blood.v120.21.3785.3785 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3785-3785 ◽

Cited By ~ 1

Author(s):

H. Jean Khoury ◽

Carlo Gambacorti-Passerini ◽

Hagop M. Kantarjian ◽

Dong-Wook Kim ◽

David Marin ◽

...

Keyword(s):

Pleural Effusion ◽

Chronic Myeloid Leukemia ◽

Disease Progression ◽

Median Time ◽

Myeloid Leukemia ◽

Research Funding ◽

Chronic Phase ◽

Cytogenetic Response ◽

Grade 3

Abstract Abstract 3785 Bosutinib (BOS) is an orally active, dual Src/Abl tyrosine kinase inhibitor (TKI). This open-label, phase 1/2 study evaluated BOS in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) following TKI failure. A total of 119 pts aged ≥18 y with prior imatinib (IM) failure plus dasatinib (DAS) resistance (n = 38), DAS intolerance (n = 50), nilotinib (NIL) resistance (n = 27), NIL intolerance (n = 1), or failure of DAS and NIL (n = 3) received BOS starting at 500 mg/d. Median age was 56 y (range, 20–79 y); 45% of pts were male; median time from CML diagnosis was 6.5 y (range, 0.6–18.3 y). Median BOS duration was 8.6 mo (range, 0.2–60.8 mo); 24% of pts are still on treatment. Dose escalation to BOS 600 mg/d occurred in 19% of pts. Time from last pt's first dose to data cutoff was 25 mo (median follow-up duration of 31.4 mo [range, 0.3–66.0 mo]). A confirmed complete hematologic response (CHR) was attained/maintained by 73% of evaluable pts (Table). The Kaplan-Meier (KM) probability of maintaining a CHR at 2 y was 67%. A major cytogenetic response (MCyR) was attained/maintained by 41%, including 32% with a complete cytogenetic response (CCyR). Among evaluable pts without a baseline CCyR, 36% (n = 37/102) achieved a MCyR, including 28 (28%) with a CCyR. The KM probability of maintaining a MCyR at 2 y was 71%. Of 86 pts with baseline mutation status, 40 (47%) pts had 19 unique Bcr-Abl kinase domain mutations, including 7 (8%) pts with T315I. Responses were seen across mutations (75% CHR, 43% MCyR excluding T315I), including those conferring resistance to other TKIs; responses in pts with T315I were low (29% CHR; 14% MCyR). Nine of 37 pts evaluated at baseline and treatment discontinuation had ≥1 new mutation (V299L, n = 4; L248V, n = 2; T315I, n = 2; F359C, n = 1; G250E, n = 1); 8 of 9 pts had discontinued BOS due to disease progression or lack of efficacy. On-treatment transformation to accelerated phase CML occurred in 5 (4%) pts after 16 to 428 d on study; no pt transformed to blast phase CML. KM-estimated on-treatment progression-free survival (PFS) at 2 y was 75%; KM-estimated overall survival (OS) at 2 y was 84% (Table). There were 23 (19%) deaths on study, with 6 deaths occurring ≤30 d after the last BOS dose. Most deaths were due to disease progression (n = 10 [8%]) or an adverse event (AE; n = 10 [8%]; including 1 treatment-related death due to gastrointestinal bleeding). Three deaths were due to unknown cause ≥509 d after the last BOS dose. Non-hematologic treatment-emergent AEs (TEAEs) seen in ≥20% of pts (all grades; grade 3/4) included diarrhea (82%; 8%), nausea (49%; 1%), vomiting (40%; 1%), rash (27%; 3%), headache (26%; 3%), fatigue (24%; 1%), and abdominal pain (20%; 1%). The incidence of individual TEAEs was generally similar across groups regardless of prior TKI exposure. Diarrhea TEAEs were predominantly grade 1/2, first reported early during treatment (median time to first event of 1.5 d [range, 1–210 d]), and transient (median event duration of 2 d [range, 1–524 d]). The incidence of pleural effusion was highest among DAS-intolerant pts (n = 11 [22%], including 3 pts with grade 3 events); for 9 of 11 pts pleural effusion had been indicated as a reason for intolerance to prior DAS. Grade 3/4 laboratory abnormalities reported in ≥10% of pts included thrombocytopenia (25%), neutropenia (19%), lymphopenia (17%), and hypermagnesemia (12%). Dose reductions and interruptions were used to manage AEs in 50% and 66% of pts. A total of 32 (27%) pts discontinued treatment due to an AE, most commonly hematologic events. In conclusion, BOS therapy continues to demonstrate durable efficacy and manageable toxicity after follow-up of ≥24 mo in CP CML following resistance or intolerance to multiple TKIs, with a majority of pts maintaining response at 2 y and few new transformations, deaths, TEAEs, or discontinuations due to AEs since the prior report ∼1 y earlier (Blood 2012;119:4303–12). n (%) IM + DAS-R IM + DAS-I IM + NIL-R IM + DAS ± NILa Total Evaluableb 37 49 25 4 115 CHR 23 (62) 39 (80) 19 (76) 3 (75) 84 (73) Evaluableb 36 44 26 4 110 MCyR 12 (33) 21 (48) 10 (39) 2 (50) 45 (41) CCyR 7 (19) 19 (43) 7 (27) 2 (50) 35 (32) Treated 38 50 27 4 119 PFS at 2 yc 70% 81% 79% 38% 75% OS at 2 yc 77% 85% 92% 75% 84% R, resistant; I, intolerant. a Includes 3 pts with prior exposure to all 3 TKIs and 1 NIL-I pt. KM rates may be unreliable due to the small number of pts in this cohort. b Received ≥1 dose of BOS and had a valid baseline response assessment. c Based on KM estimates Disclosures: Gambacorti-Passerini: Pfizer Inc: Consultancy, Research Funding; Novartis, Bristol Myer Squibb: Consultancy. Kantarjian:Pfizer: Research Funding. Kim:BMS, Novartis, Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marin:Novartis: Research Funding; BMS: Research Funding. Dorlhiac-Llacer:Novartis, Bristol Myer Squibb, Pfizer: Research Funding. Bullorsky:Novartis, BMS: Consultancy, Speakers Bureau. Leip:Pfizer Inc: Employment. Kelly:Pfizer Inc: Employment, Equity Ownership. Turnbull:Pfizer Inc, l3/Inventiv Clinical Solutions: Employment. Besson:Pfizer Inc: Employment. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding.

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Baseline Characteristics Of Patients With Chronic Myeloid Leukemia In a Prospective Observational Study (SIMPLICITY)

Blood ◽

10.1182/blood.v122.21.4026.4026 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4026-4026 ◽

Cited By ~ 1

Author(s):

Jorge E. Cortes ◽

Rüdiger Hehlmann ◽

Carlo Gambacorti-Passerini ◽

Stuart Goldberg ◽

H. Jean Khoury ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Chronic Myeloid Leukemia ◽

Clinical Research ◽

Myeloid Leukemia ◽

Research Funding ◽

Chronic Phase ◽

First Line ◽

Historical Cohort ◽

Prospective Cohorts

Abstract Background Oral BCR-ABL tyrosine kinase inhibitors (TKIs), including imatinib (IM), dasatinib (DAS) and nilotinib (NIL), have improved survival in chronic-phase chronic myeloid leukemia (CP-CML). Few data are available that compare TKIs in daily clinical practice across multiple regions. Methods SIMPLICITY is an ongoing observational cohort study of adult patients with newly diagnosed CP-CML receiving first-line treatment with IM, DAS or NIL in the USA and Europe (Eu) outside of clinical trials (NCT01244750). The primary objective is to assess effectiveness of these TKIs in clinical practice. The study includes three ‘prospective’ cohorts of patients treated with IM, DAS or NIL since 2010 (the study opened after first-line approval of all three TKIs) and a ‘historical’ cohort treated with IM since 2008. Preliminary baseline demographics are presented for prospective cohorts. Results 860 prospective patients (Eu: 32%, USA: 68%) were enrolled through June 20, 2013, receiving IM (n=399), DAS (n=229) or NIL (n=232). Median age at initiation of first-line TKI was 56 years, with significant differences in pairwise comparisons between DAS and IM and NIL and IM (Table). Demographics were consistent across cohorts. Only 30% of patients had Hasford or Sokal scores recorded. ECOG performance status (PS) was available in 54% of patients. The number of baseline comorbidities per patient (mean: 3.2 + 2.7) was balanced across cohorts; 51% of patients presented with ≥3 comorbidities. Patients in the IM cohort had a higher prevalence of gastrointestinal comorbidities (P=.006 and .007 for DAS vs IM and NIL vs IM, respectively), and the NIL cohort had a higher prevalence of musculoskeletal comorbidities than the DAS cohort (P=.015). The proportions of patients with cardiovascular comorbidities were 38%, 36% and 42% in the DAS, NIL and IM cohorts, respectively, consisting primarily of hypertension (31%) and hyperlipidemia (17%) (P>.05 across cohorts). Coronary artery disease was present in 9%, cardiac arrhythmias in 6%, myocardial infarction in 3% and peripheral arterial disease in 2% of patients. The proportion of patients with diabetes was 10%. Clinicians reported effectiveness as the most common reason for TKI selection; familiarity and cost were also cited as reasons for IM selection (P<.001 vs DAS and NIL). Comorbidities were not drivers of TKI selection in this analysis. Conclusions This is the first report from the prospective cohorts of SIMPLICITY. Demographics were consistent across cohorts. Overall, the SIMPLICITY population is older with potentially more comorbidities than patients enrolled in first-line clinical trials with restrictive inclusion criteria (NEJM 2003 348 994; NEJM 2010 362 2260; NEJM 2010 362 2251). Initial TKI selection does not appear to be driven by baseline comorbidity, rather by perceived effectiveness, cost and familiarity. Hasford/Sokal scores were not recorded in the majority of patients prior to starting first-line TKI therapy. Outcomes data are being collected across cohorts that will inform about a multi-region population treated outside clinical trials. Disclosures: Cortes: Ariad: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Teva: Consultancy, Honoraria, Research Funding. Hehlmann:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding. Gambacorti-Passerini:Bristol-Myers Squibb: Consultancy; Pfizer: Honoraria, Research Funding. Goldberg:Bristol-Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Novartis Oncology: Honoraria, Research Funding, Speakers Bureau; Ariad: Honoraria, Research Funding, Speakers Bureau. Khoury:Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Ariad: Honoraria; Teva: Honoraria. Mauro:Novartis Oncology: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Speakers Bureau. Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding. Paquette:Ariad: Consultancy; Incyte: Consultancy, Honoraria; Novartis: Consultancy. Foreman:ICON Clinical Research: Employment, My employer ICON Clinical Research receives research funding from pharmaceutical companies including manufacturers of CML drugs Other. Mohamed:Bristol-Myers Squibb: Employment. Zyczynski:Bristol-Myers Squibb: Employment. Hirji:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment.

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Two-Year Consolidation By Nilotinib Is Associated with Successful Treatment Free Remission in Chronic Myeloid Leukemia with MR4.5: Subgroup Analysis from STAT2 Trial in Japan

Blood ◽

10.1182/blood.v128.22.1889.1889 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1889-1889 ◽

Cited By ~ 7

Author(s):

Naoto Takahashi ◽

Chiaki Nakaseko ◽

Kaichi Nishiwaki ◽

Hisashi Wakita

Keyword(s):

Chronic Myeloid Leukemia ◽

Subgroup Analysis ◽

Myeloid Leukemia ◽

Research Funding ◽

Second Generation ◽

Second Line ◽

First Line ◽

Prior Therapy ◽

Line Therapy ◽

Treatment Free Remission

Abstract Background Nilotinib (NIL) is a second-generation tyrosine kinase inhibitor (TKI) that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). Superior rates of deeper molecular responses (DMR) were achieved with NIL vs. imatinib (IM) in patients newly diagnosed with CML in chronic phase (CML-CP) in the ENESTnd trial. In addition, the ENESTcmr study demonstrated that switching to NIL after a minimum of 2 years on IM led to increased rates of DMR vs. remaining on IM. Switching to NIL treatment for 2 years safely led to MR4,5 (BCR-ABLIS…0.0032%) in 47.5% of patients with major molecular response (MMR) on long-term IM therapy in our STAT1 trial. Recently, treatment free remission (TFR) was proposed as one of the goals in CML treatment. Indeed, prospective trials suggest that IM therapy may be safely and successfully discontinued in 40% of CML patients with MR4.5. STAT2 is the first study to evaluate the efficacy of two-year consolidation by NIL for successful TFR in patients with CML-CP who had achieved MR4.5. Before enrolling in STAT2, some patients were treated by not only IM but also NIL because of MMR but no MR4.5 after IM therapy, and some patients changed over from STAT1 to STAT2. Here, we present the results of the subgroup analysis from STAT2 based on the prior treatments at the time of entry into the study. Methods In the STAT2 trial, patients who achieved MR4.5 on IM front line therapy (subgroup 1; SG1) or NIL second line therapy after IM therapy (subgroup 2; SG2) were eligible and NIL was given twice daily at the dose of 600 mg/day for 2 years in consolidation phase. The primary endpoint of STAT2 was the proportion of patients with successful TFR, defined as no confirmed loss of MR4.5 (2 consecutive IS RQ-PCR tests), within the first 12 months of TFR phase. Thirty-five institutions in STAT study group participated. The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was signed by all patients according to institutional guidelines. The study was approved by all institutional review boards and registered with UMIN-CTR (000005904). Results Between July 2011 and December 2012, 96 patients were enrolled in STAT2. Among 96 patients, 50 patients were treated by IM first line only as prior therapy (SG1). On the other hand, 40 patients were treated by IM first line and NIL second line including 21 patients who changed over from STAT1 to STAT2 because they achieved MR4.5 (SG2). Six patients were excluded in this analysis because second generation TKIs were taken as a first line therapy. Among patients treated by NIL for 2 years in this study, 40/50 (80%; 95% CI, 68.4%-88.7%) in SG1 and 33/40 (82.5%; 95% CI, 69.6%-91.5%) in SG2 entered the TFR phase, respectively. The median age was 54.5 years in SG1 and 56.0 years in SG2. The ratio of men to women was 26:14 in SG1 and 18:15 in SG2. The total duration of TKI treatment was 110 months for the SG1 with a median of 86 months of IM, and 24 months of NIL, and 93 months in SG2 with a median of 62 months of IM, and 31 months of NIL,, respectively. All patients achieved MR4.5 at the time of entry into the study and the median time to MR4.5 was 47 months in SG1 and 60 months in SG2.The proportion of patients who maintained TFR at 12 months after stopping NIL was similar across the 2 subgroups: 25/40 (62.5%; 95% CI, 48.3%-77.3%) in SG1, and 23/33 (69.7%; 95% CI, 54.0%-82.5%) in SG2. The Kaplan-Meier (KM) analysis of TFR survival showed that in the 2 subgroups, the majority of events occurred within the first 6 months after stopping NIL (Figure 1). There were no significant differences between these 2 subgroups. Conclusion After two-year consolidation by NIL of CML-CP patients who achieved MR4.5, the TFR rate was 67.9% (90%CI: 58.2% to 76.6%) at 12 months in the STAT2 trial. In the present analysis looking at the prior TKI exposure, the TFR rate was similar in patients treated with IM first line only or who switched from IM to NIL before entering the study, despite the fact that the treatment duration of switched patients was slightly shorter. These findings suggest that two-year consolidation by NIL is associated with successful TFR in CML with MR4.5 that was achieved with IM alone or after switching to NIL. Figure Kaplan-Meiercurve of TFR survival in the 2 subgroups based onthe prior treatmentsbefore two-year consolidation by NIL, IM first line only as prior therapy (subgroup1) and IM first line and NIL second line (subgroup2). Figure. Kaplan-Meiercurve of TFR survival in the 2 subgroups based onthe prior treatmentsbefore two-year consolidation by NIL, IM first line only as prior therapy (subgroup1) and IM first line and NIL second line (subgroup2). Disclosures Takahashi: PFIZER: Honoraria, Research Funding; BMS: Honoraria; NOVARTIS PHARMA: Honoraria, Research Funding. Nakaseko:BMS: Honoraria, Research Funding; PFIZER: Honoraria, Research Funding; NOVARTIS: Honoraria. Nishiwaki:Novartis PHARMA: Research Funding.

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Novel Targeted Therapies and Their Impact on Survival from Multiple Myeloma (MM) and Chronic Lymphocytic Leukaemia (CLL) in the Real World

Blood ◽

10.1182/blood.v128.22.3546.3546 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3546-3546

Author(s):

Alexandra G Smith ◽

Timothy Bagguley ◽

Eve Roman ◽

Andy C Rawstron ◽

James R Bailey ◽

...

Keyword(s):

Multiple Myeloma ◽

Chronic Lymphocytic Leukaemia ◽

Combination Chemotherapy ◽

Real World ◽

Research Funding ◽

Lymphocytic Leukaemia ◽

Alkylating Agents ◽

First Line ◽

Time Periods ◽

Line Chemotherapy

Abstract Introduction The treatment landscape for many mature B-cell malignancies is evolving rapidly, with patients and clinicians facing increasingly complex choices about therapeutic options that differ in efficacy, toxicity and cost. Accounting for around a quarter of all haematological cancer diagnoses, multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) are two conditions where increases in the number and combinations of potentially life-prolonging therapies has been particularly marked; ranging from the use of single alkylating agents to immunomodulatory drugs and proteasome inhibitors for MM, and combination chemotherapy, immuno-chemotherapy, novel monoclonal antibodies and tyrosine-kinase inhibitors (TKIs) for CLL. Contemporary data enabling the success of such therapeutic changes to be evaluated in the general patient population is, however, lacking. With centralized diagnostics and a unified clinical network covering a catchment population of 4 million, the UK's Haematological Malignancy Research Network (www.hmrn.org) was specifically established to provide timely real-world data to answer such questions; and findings from this unique population-based cohort are reported here. Methods Patients newly diagnosed 2004-13 with MM (n=2084) or CLL (n=1866) were followed-up until January 2016. Demographic, prognostic, first-line treatment and outcome data for the time-periods 2004-07, 2008-10 and 2011-15 were examined using standard statistical methods; relative survival (RS) was estimated using national life tables. Results The median age at diagnosis of MM was 73 years (17% <60 years); 39% of patients presented with an ISS score of III and 25% were asymptomatic (CRAB score 0). In total, 1514 (73%) patients received first-line chemotherapy either at diagnosis or as a consequence of disease progression. Regimens were classified by their main agent, and the therapy changes over the 11-year period are shown in Figure 1a; in 2004-07, 44% of treated patients received single-agent alkylating therapy, in 2008-10 76% were treated with combination immunomodulatory therapy and by 2011-15 this had increased to 92%. The 3-year overall survival (OS) and RS estimates for all patients combined were 45.9% (95% Confidence Interval 43.4-48.4) and 52.0% (49.1-54.8) respectively. Differences in outcome by treatment year are clearly evident (Figure 1b): 3-year RS 2004-07, 46.5% (41.8-51.2); 2008-10, 48.4% (43.5-53.2); and 2011-15, 62.1% (56.8-66.9). The improvement in survival for patients treated in 2011-15 compared to 2004-07 was confirmed by multivariate Cox regression (Hazard Ratio 0.65, 0.56-0.76). With a median diagnostic age of 71 years (18% <60 years); the majority of CLL patients had early-stage disease (BinetStage A, 78%). In total 547 patients were treated with first-line chemotherapy, with the regimen again changing over time (Figure 1c). Patients treated 2004-07 generally received single alkylating agents (56%) or combination chemotherapy (42%), by 2008-10 32% of patients had a monoclonal antibody added to chemotherapy (chemo-immunotherapy), increasing to 72% among those treated 2011-15. The 3-year OS and RS for all treated patients combined were 69.5% (65.3-73.3) and 80.3% (75.5-84.3) respectively. However, there was no incremental statistically significant change in 3-year RS (Figure 1d); 2004-07, 76.4% (65.2-84.4); 2008-10, 78.3% (69.8-84.6); and 2011-15 84% (76.3-89.4); and taking 2004-07 as the reference, the corresponding hazard ratios for the 3 time-periods were 1 (reference), 1.00 (0.78-1.37) and 0.79 (0.58-1.09). The cost implications of the changing treatment landscape are currently being examined, and by December 2016 the findings presented above will include more recently diagnosed patients (2014-15), which is particularly pertinent for CLL, where a step-change may have occurred due to the introduction of TKIs. Conclusions Our analyses confirm that first-line chemotherapy for MM and CLL is changing markedly; highlighting the importance of monitoring the impact of therapeutic change in a real-world setting. The improvement in MM survival currently contrasts with CLL, suggesting that encouraging results from clinical trials may not always translate directly into similar improvements at a population level. Clearly, additional analysis of data from patients diagnosed >2014 are required. Figure 1 Figure 1. Disclosures Smith: Novartis: Research Funding; Janssen-Cilag: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Glycomimetics: Consultancy. Patmore:Roche: Honoraria; Janssen Cilag: Honoraria.

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Peripheral Blood Flow-Cytometry Chronic Myeloid Leukemia Stem Cells Detection and Quantification during Tyrosine Kinase Inhibitors Therapy

Blood ◽

10.1182/blood.v128.22.942.942 ◽

2016 ◽

Vol 128 (22) ◽

pp. 942-942 ◽

Cited By ~ 2

Author(s):

Monica Bocchia ◽

Lara Aprile ◽

Santina Sirianni ◽

Elisabetta Abruzzese ◽

Antonella Gozzini ◽

...

Keyword(s):

Flow Cytometry ◽

Myeloid Leukemia ◽

Research Funding ◽

Kinase Inhibitors ◽

Fish Analysis ◽

Molecular Response ◽

Line Treatment ◽

First Line ◽

Qrt Pcr ◽

First Line Treatment

Abstract Introduction: In chronic myeloid leukemia (CML), tyrosine Kinase Inhibitors (TKIs) treatment is a potentially life-time therapy for the majority of patients (pts), as few of them, only after achieving a deep and stable molecular response, may discontinue TKIs without recurrence of disease. Available data suggest that relapse after TKIs discontinuation is due to the persistence of leukemic stem cells (LSCs) intrinsically resistant to TKIs. Survival of CML LSCs may be the consequence of activation of several pathways BCR-ABL1 independent. qRT-PCR, the most sensitive assay to monitor disease status in CML pts, may be inappropriate to quantify residual quiescent CML LSCs that are transcriptionally silent. Therefore, the possibility to easily quantify LSCs during TKIs treatment is a great opportunity to better understand the behavior of residual LSCs and potentially to identify those pts candidates to safely discontinue TKIs. Recently, Valent et al described that CD34+/CD38-/Lin- CML LSCs specifically co-express dipeptidylpeptidase IV (CD26) and that CD26 is a potential biomarker for the quantification and isolation of CML LSCs, in bone marrow samples of CML patients. Furthermore, Culen et al. quantified CD26+ LSCs bone marrow compartment in 31 CML patients at diagnosis and their number appears to correlate with response to TKIs treatment. In the present study we wanted to explore the feasibility, rate and potential implication of detecting CD26+ LSCs in peripheral blood (PB) from CML pts during TKI treatment. Methods: CML pts during first line treatment with any approved TKIs, referring to several Italian Hematology Centers, entered this non interventional cross sectional study after signing a proper informed consent. During a routine follow up visit, in which pts were checked for molecular response by standard PB qRT-PCR BCR-ABL1 analysis, additional 3 mls of PB were collected in EDTA and sent within 24 hours to Siena Hematology Lab to detect CD34+/CD38-/CD26+ LSCs by multicolor flow cytometry. After red blood cells lysis, cells were incubated with anti CD45 (BD Biosciences), CD34 (581), CD38 (HIT2), CD26 (M-A261) (BD Pharmigen). After washing, acquisition and analysis were performed by FACSCanto II (BD Biosciences, NR Nannini) using DIVA 8 software (BD, Biosciences). CD45+ cells acquired for each sample ranged from 500,000 to 1,000,000. Isotype controls were included in each staining. In 5 pts a FISH analysis of PB sorted CML LSCs population was also performed. Results: to validate our assay we first performed a FISH analysis of both PB sorted CD34+/CD38-/CD26+ and CD34+/CD38-/CD26- in 5 CML patients at 3-6 months after starting treatment, confirming Ph+ cells only in the CD26+ fraction. Afterward, we checked for circulating CML LSCs a total of 202 CML pts in first line treatment with TKIs for a median of 39 months (range 1-175). Type of TKI, length of treatment, molecular response and quantification of LSCs are summarized in Table 1. PB CML LSCs were detectable in 146/202 (72.3%) pts with a median number of CD26+ of 0,0165 cells/µL (range 0,0018-0,66). Kendall rank correlation coefficient used to analyze the relation between the measurable variables showed no correlation between BCR-ABL/ABLIS ratio (median 0,004 range 0-61) and number of residual LSCs (r 0.118 p=0.097). In 56/202 (27.7%) pts CD26+ LSCs were undetectable, yet we found no correlation with the concomitant degree of molecular response. Conclusions: this study represents the first attempt to measure in a large cohort of CML patients residual circulating LSCs during TKIs treatment. In our hands PB LSCs flow-cytometry assay appeared feasible, specific and sensitive and thus suitable for routine monitoring. As expected, the majority of CML patients, even in deep molecular response, still harbor residual LSCs and the number of PB CD26+ did not correlate with the number of BCR-ABL1 copies. This evidence suggests that the molecular response refers to transcriptionally active CML progenitor cells and not to quiescent, TKIs resistant, CML LSCs. Prospective studies evaluating the behavior of PB CML LSCs during different TKIs treatment, as well as studies monitoring PB CD26+ in CML pts that discontinued TKIs treatment are ongoing. Our goal is to rule out the impact, if any, of a "stem cell response" in addition to the standard molecular response in the management of CML patients mainly to identify those pts candidates for a safe TKI discontinuation. Disclosures Bocchia: Janssen: Honoraria; Novartis: Honoraria; Bristol-Myers Squibb: Honoraria. Aprile:Novartis: Honoraria. Castagnetti:Pfizer: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; ARIAD Pharmaceuticals: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Tiribelli:Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau. Breccia:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Rosti:Roche: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

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Quality of life of acute myeloid leukemia patients in a real-world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18525 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18525-e18525

Author(s):

Bhavik J. Pandya ◽

Anna Hadfield ◽

Bruno C. Medeiros ◽

Samuel Wilson ◽

Cat N. Bui ◽

...

Keyword(s):

Quality Of Life ◽

Acute Myeloid Leukemia ◽

Real World ◽

Myeloid Leukemia ◽

Line Treatment ◽

First Line ◽

Real World Setting ◽

First Line Treatment ◽

Acute Myeloid

e18525 Background: There is currently limited data on the quality-of-life (QoL) of patients with acute myeloid leukemia (AML) in the real-world setting. The objective of this analysis was to understand the impact of AML on patients receiving first-line treatment vs those who were relapsed/refractory to first-line treatment and therefore on later lines of therapy. Methods: The Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey involving 61 US hematologists/hemato-oncologists and their consulting AML patients, was conducted between February–May 2015. Physicians provided details on patient demographics and clinical information. Each patient was asked to complete both the EQ-5D-3L and Functional Assessment of Cancer Therapy Leukemia (FACT-Leu). Scores range from −1.09–1 (EQ-5D-3L) and 0–176 (FACT-Leu), where a higher score indicates a better QoL. Data from physician-completed record forms and corresponding patient self-completion forms on a matched sample of 75 patients were analyzed. Results: Of the patients who took part in the survey, 75% (n = 56) were receiving first-line treatment for AML and 25% (n = 19) were relapsed/refractory to first-line treatment and had progressed to later lines of therapy. The first-line patients had a mean age of 56.6 years and an average of 2.1 symptoms whereas the relapsed/refractory patients had a mean age of 56.9 years and an average of 2.4 symptoms, according to the physician. First-line patients may have a directionally better QoL scores than those on later lines of therapy, according to both the EQ-5D (0.75 and 0.71 respectively, P= .51) and the FACT-Leu (103.7 and 92.5 respectively, P= .098) measures. Results from the FACT-Leu-Physical Well-Being sub-domain show that relapsed/refractory patients were significantly more likely than first-line patients to be affected physically by their AML condition (13.0 and 17.6 respectively, P= .005). Conclusions: AML patients who have relapsed or become refractory to first-line treatment report worse QoL than those still on first-line treatments. These observational data shows a need for effective and tolerable treatments that can maintain or improve patients’ QoL, especially for patients with relapsed or refractory disease.

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Real-world prescribing patterns in acute myeloid leukemia in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18524 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18524-e18524 ◽

Cited By ~ 1

Author(s):

Bruno C. Medeiros ◽

Bhavik J. Pandya ◽

Anna Hadfield ◽

Samuel Wilson ◽

Cynthia Mueller ◽

...

Keyword(s):

United States ◽

Acute Myeloid Leukemia ◽

Real World ◽

High Intensity ◽

Myeloid Leukemia ◽

Patient Characteristics ◽

The United States ◽

First Line ◽

Low Intensity ◽

Acute Myeloid

e18524 Background: The effective treatment of patients with acute myeloid leukemia (AML) remains a challenge in clinical practice. This analysis describes the patient characteristics and real-world use of AML treatments in the United States for patients on high- and low-intensity treatment. Methods: Data from the Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey conducted between February–May 2015, were analysed. A total of 61 hematologist/hem-oncologists, across academic, non-academic and office-based practice locations, provided data on 457 AML patients. Patient characteristics were derived from physician-completed patient record forms where each physician was asked to provide treatment details, including the treatment intensity, for each line of therapy. Results: A total of 91% (n = 415) of patients included in this analysis were previously untreated for AML. Patients had a mean age of 60 years and been diagnosed with AML for a median of 5.0 months. At first-line induction therapy, over half (53%; n = 241) of the patients were initiated on a high-intensity treatment, the most common regimen being cytarabine plus anthracycline (61%; n = 147). The remaining 47% (n = 216) of patients received a low-intensity induction therapy such as low dose cytarabine monotherapy (28%, n = 61), azacitidine monotherapy (25%, n = 54), or decitabine monotherapy (21%, n = 45). Over half (55%, n = 62) of patients suited to high intensity treatment went on to receive cytarabine monotherapy during the consolidation phase of their first-line treatment. Conclusions: According to treating physicians, the large majority of patients receive traditional, well-established therapies at first-line induction for AML. Whilst cytarabine combinations dominate the high-intensity treatment setting, the hypomethylating agents, azacitidine and decitabine, are frequently used for those more suited to low-intensity treatment.

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