scholarly journals Treatment Patterns and Outcomes of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMA) in the United States (US)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-16
Author(s):  
Timothy S. Pardee ◽  
Jessica Oschwald ◽  
Esprit Ma ◽  
Tao Xu ◽  
Melissa Montez ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Community Setting ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
The Past ◽  
The Us

Introduction: AML is an aggressive disease with poor prognosis that predominantly affects older adults. Due to advanced age and associated comorbidities, many patients are not fit for intensive induction chemotherapy. Monotherapy with HMAs such as azacitidine (AZA) or decitabine (DEC) is often still considered as standard of care for these patients, despite mixed evidence from studies regarding the benefit of HMAs alone (Duchmann & Itzykson. Int J Hematol 2019). The aim of the current study is to evaluate patient characteristics, treatment patterns and outcomes of patients with AML treated with HMA monotherapy as first line (1L) in clinical practice in the US. Methods: This is a retrospective observational study of the Flatiron Health database; a nationwide, longitudinal, demographically and geographically diverse database representing more than 2.4 million patients with cancer in the US. The database contains de-identified data derived from electronic health records from over 280 cancer clinics, which are predominantly community oncology practices. Patients ≥18 years, diagnosed with AML between 1/1/2014 and 3/30/2020 (excluding acute promyelocytic leukemia and clinical trial enrollment), and who received HMAs as 1L treatment ≤30 days from AML diagnosis were evaluated. Descriptive analyses were conducted on patient characteristics and treatment patterns. Kaplan-Meier analyses were used to estimate time to last administration (TTLA; from initiation to last observed administration before death, end of follow-up or a gap of 60 days) and median overall survival (OS). Results: A total of 2589 patients with an AML diagnosis were included for analysis, where 574 (22%) were treated with 1L HMAs (AZA: n=341 [59%]; DEC: n=233 [41%]). The median age of 1L HMA patients was 79 years with 63% male. Most patients were treated in the community setting (n=511 [89%]; median age: 79 years); those treated in academic centers were slightly younger (n=63 [11%]; median age: 77 years). Characteristics for non-antecedent hematological disorder (AHD)-AML (n=327) and AHD-AML (n=247) patients are presented in Table 1. Median TTLA with 1L HMA was 77 days with a median of 3 cycles of both AZA and DEC. Of the 168 patients who received second-line (2L) therapy, 82% (n=138) received another low-intensity therapy or combination (of which only 14 received targeted therapies) (Figure 1). Overall, 44% of 1L HMA patients (n=254) had evidence of molecular testing before 1L treatment initiation (this was more common in later years). Of the 228 patients tested for FLT3, 30 (13%) were FLT3 positive; 7 (23%) FLT3-positive patients were treated with 2L or third-line (3L) FLT3-targeted therapies (gilteritinib, midostaurin or sorafenib). Of the 152 patients tested for IDH1/2, 35 (23%) were IDH1/2 positive; 5 (14%) IDH1/2-positive patients were treated with 2L or 3L targeted agents (enasidenib or ivosidenib). A median OS of 6.3 months (95% CI: 5.5-7.5) was observed in the overall 1L HMA cohort. Median OS in 1L HMA patients did not differ with respect to different types of AML (non-AHD-AML: 6.6 [95% CI: 5.5-7.9] months; AHD-AML: 6.0 [95% CI: 4.8-7.5] months, p=0.34) or practice setting (community: 6.0 [95% CI: 5.3-7.0] months; academic: 8.3 [95% CI: 6.9-13.3] months, p=0.14). One-year OS was 31.4% and 30.1% for non-AHD-AML and AHD-AML patients, respectively. Patients treated in the community setting had numerically lower 1-year OS (29.7% [95% CI: 25.8-34.3]) than those treated in the academic setting (39.5% [95% CI: 28.6-54.6]), which reflects the higher rates of 2L treatment in academic practice, though this analysis is unadjusted. Conclusions: This new database enabled a detailed analysis of 1L HMA-treated patients with newly diagnosed AML in routine clinical practice predominantly in the community setting. 1L HMA patients have poor survival outcomes (median OS 6.3 months) which are comparable to other real-world data from SEER-Medicare (Zeidan et al. Blood Adv 2020; median OS 7-8 months; median age: 77 years); but shorter than the median OS of 9-10 months observed in 1L HMA-treated AML patients in clinical trials (DiNardo et al. EHA 2020). Limitations of the study included limited conduct of bone marrow biopsies for response and lack of transfusion data. The observed survival outcomes highlight the importance of further treatment advances to address the unmet need in older patients with AML ineligible for intensive induction chemotherapy. Disclosures Pardee: Rafael: Research Funding; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Pharmacyclics: Speakers Bureau; Rafael Pharmaceuticals: Consultancy; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy; Genentech, Inc.: Consultancy; Karyopharm: Research Funding. Oschwald:Roche Products Limited: Current Employment. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Montez:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ramsingh:Genentech, Inc.: Current Employment; NEKTAR: Current equity holder in publicly-traded company; Exelixis: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Hong:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Choi:AbbVie: Current Employment, Current equity holder in publicly-traded company. Flahavan:Roche Products Ltd.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. OffLabel Disclosure: Discussion will include the use of decitabine for the treatment of AML.

scholarly journals Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4086-4086
Author(s):  
Anthony R. Mato ◽  
Arliene Ravelo ◽  
Tu My To ◽  
Robert Schuldt ◽  
Juliana M.L. Biondo
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
Treatment Regimens ◽  
The Past ◽  
Oral Agents ◽  
The Us ◽  
Testing Patterns ◽  
Over Time

Abstract Background: There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration. Here, we assessed the evolution of molecular testing patterns, treatment patterns, and clinical outcomes over time in patients receiving 1L CLL treatment in a real-world US database. Methods: This was a retrospective cohort study using the Flatiron Health database, a longitudinal database comprising de-identified, patient-level, structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. Patients aged 18 years and older who were diagnosed with CLL and initiated 1L treatment between December 2015 and December 2020 were selected. Participants who took part in a clinical trial in any line of therapy, or who had any other primary cancer diagnosis, were excluded. Baseline characteristics, including testing patterns, at initiation of 1L treatment were assessed using descriptive statistics. Treatment patterns and outcomes, such as time to next treatment or death (TTNTD), were analyzed. Kaplan-Meier analysis was used to estimate TTNTD. Results: Among 3654 patients with treatment-naive CLL who were selected from the de-identified database, the mean age at 1L treatment initiation was 70 years (range, 29-85); 64.3% of patients were male; 72.1% were White, 8.2% Black, 3.9% Hispanic/Latino, 1.0% Asian, and 14.9% were of other ethnicity/race. Approximately one-third (34.7%) of patients had Rai stage 0-I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage. Testing patterns: The majority of identified patients (3202/3654; 87.6%) had undergone cytogenetic testing, fluorescence in situ hybridization, or IGHV mutation testing. Compared with 2015-2016, testing rates were higher in 2019-2020 for chromosome 17p deletion (del(17p); 36.1% vs 45.7%, respectively; p<0.001) and for IGHV mutation status (84.7% vs 89.2%, respectively; p=0.003). Overall, 11.0% of patients had del(17p). Of those tested for IGHV (1472/3654; 40.3%), 58.3% had unmutated IGHV. Treatment patterns: The 10 most commonly used 1L CLL treatments, which overall represented 91.8% of all 1L treatments, and their evolution over time, are reported in Table 1. Of the patients receiving these top 10 1L treatment regimens overall, 45.7% received regimens including novel targeted oral agents, 33.4% received chemo-immunotherapy (CIT), and 19.7% received anti-CD20 monotherapy. Evaluation of each 2-year period shows that treatment patterns for the top 10 1L treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015-2016) to 63.8% (2019-2020) (p<0.001), while use of CIT and chemotherapy decreased over time (Table 2). Approximately 30.0% (1088/3654) of 1L-treated patients went on to receive second-line treatments. Outcomes: Median TTNTD was 34.4 months for all patients receiving 1L CLL treatment, and 36.5 months for patients who received the 10 most common 1L treatments across the 6-year study period (n=3360). Median TTNTD was 47.0 months for patients who received novel targeted oral agents and 41.5 months for patients who received CIT (unadjusted p=0.16). When evaluating outcomes in patients with high-risk cytogenetics, median TTNTD was 29.1 months for patients with del(17p) and 37.2 months for those with unmutated IGHV, but was longer in those patients who received treatment with novel targeted oral agents (median TTNTD of 43.9 and 46.7 months, respectively; Table 3). Conclusions: This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups. Following on from this, a comparative study of TTNTD for novel oral agents versus CIT, and analyses of outcomes of different sequencing of therapies, will be conducted. Figure 1 Figure 1. Disclosures Mato: Nurix: Research Funding; Johnson and Johnson: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; MSKCC: Current Employment; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ravelo: Genentech, Inc.: Current Employment; Roche Holdings: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. To: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Schuldt: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Biondo: Genentech, Inc.: Current Employment; Roche: Current holder of individual stocks in a privately-held company.

scholarly journals Real-World Effectiveness of First-Line (1L) Dasatinib Versus 1L Imatinib in Newly Diagnosed Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Andrew J Klink ◽  
Scott Justin Keating ◽  
John Brokars ◽  
Arianna Kee ◽  
Ronda Copher ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Research Funding ◽  
Patient Characteristics ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Risk Patients ◽  
Advisory Role

Introduction: The safety and efficacy of 1L dasatinib and 1L imatinib was established in the pivotal DASISION and IRIS trials; however, limited real-world evidence exists for the comparative effectiveness of these agents among US patients with CP-CML treated in routine clinical practice. As such, real-world data are needed to assess the outcomes of imatinib- and dasatinib-treated patients in a pragmatic setting. Additionally, recent data suggest that second generation tyrosine kinase inhibitors (TKIs), including dasatinib, may be beneficial in certain CP-CML populations, which may be underrepresented in clinical trials (e.g., high risk, elderly, or high body mass index [BMI]). This study examined the real-world clinical response rates and time to response associated with 1L dasatinib or 1L imatinib among patients with CP-CML, as well as in subgroups defined by Sokal risk, age, and BMI. Methods: A retrospective, observational, US multi-site cohort study was conducted among adults with newly diagnosed Philadelphia chromosome-positive CP-CML treated with 1L dasatinib or 1L imatinib between January 2014 and September 2018. Patients had at least 1 year of follow-up after 1L initiation and did not have another malignancy or treatment as part of any clinical trial for CML. Oncologists collected data from eligible patient charts, including patient characteristics, treatment details, response to dasatinib or imatinib, and survival. Response was classified as major molecular response (MMR) and deep molecular response (DMR: 4.5-log reduction in BCR-ABL1 transcript levels) by physician report. Patient characteristics and outcomes were summarized using descriptive statistics for dasatinib and imatinib; results were reported in aggregate and stratified by Sokal risk (low and intermediate/high), age (< 65 and ≥ 65 years old), and BMI (low/normal [< 25 kg/m2] and high [≥ 25 kg/m2]). Comparisons were made by chi-square or Fisher's exact test for categorical variables, t-test or Wilcoxon test for continuous variables, log-rank test for overall survival (OS), and Cox proportional hazard models using Fine and Gray's method to account for competing risks in estimating differences in time to response across groups. Results: Among the patients treated with 1L dasatinib (n = 309) and 1L imatinib (n = 304), median follow-up time was 27.4 and 28.9 months, respectively. Most patients initiated dasatinib at 100 mg (82%) or imatinib at 400 mg (95%). Dose reductions were more common among dasatinib patients vs imatinib (15% vs 7%, P < 0.01), though fewer dasatinib-treated patients discontinued for any reason (15% vs 28%, P < 0.01). Higher rates of MMR were seen in dasatinib vs imatinib patients (79% vs 65%, P < 0.01) and median time to MMR was shorter with dasatinib vs imatinib (11.9 vs 14.7 months, P < 0.01). Similarly, higher rates of DMR were seen among dasatinib vs imatinib patients (44% vs 25%, P < 0.01) along with a shorter median time to DMR with dasatinib vs imatinib (30.3 vs 66.1 months, P < 0.01). Among patients with intermediate/high Sokal risk, as well as those < 65 years old, rates of MMR and DMR were higher and achieved earlier with dasatinib vs imatinib (all P < 0.01) (Table). Low-risk patients treated with dasatinib had higher rates of DMR vs imatinib (60% vs 32%, P = 0.01). Among patients ≥ 65 years old, rates of MMR and DMR were numerically higher with dasatinib vs imatinib, though differences were not significant at α = 0.05. Across both BMI strata, rates of MMR and DMR were higher with 1L dasatinib vs 1L imatinib (all P < 0.05). In the overall population, dasatinib patients had superior OS compared to those treated with imatinib (98% vs 89%, P < 0.01). Conclusions: In real-world clinical practice, a greater proportion of patients with CP-CML treated with 1L dasatinib achieved MMR and DMR and also achieved these responses earlier vs 1L imatinib. These clinically meaningful improvements were also observed across patient subgroups stratified by Sokal risk, age, and BMI. These findings from real-world US data were consistent with DASISION, demonstrating that dasatinib yields better outcomes among patients with CP-CML, with the novel findings of improved OS and improved outcomes in certain subgroups, including a higher rate of DMR among low-risk patients. Disclosures Klink: Cardinal Health: Current Employment, Current equity holder in publicly-traded company. Keating:Bristol Myers Squibb: Current Employment. Brokars:Bristol Myers Squibb: Current Employment. Kee:Bristol Myers Squibb: Current Employment. Copher:Bristol Myers Squibb: Current Employment. Stwalley:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Feinberg:Cardinal Health: Current Employment. Jabbour:Takeda: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding.

scholarly journals Treatment Patterns and Outcomes of Multiple Myeloma (MM) with Chromosome Translocation (11;14) in United States (US) Routine Clinical Practice

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-43
Author(s):  
Shebli Atrash ◽  
Evelyn M. Flahavan ◽  
Tao Xu ◽  
Esprit Ma ◽  
Sudeep Karve ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Community Setting ◽  
B Cell Lymphoma ◽  
Chromosome Translocation ◽  
Routine Clinical Practice ◽  
Chromosome 1 ◽  
Test Results ◽  
Publicly Traded ◽  
The Us

Introduction: MM is an incurable disease with risk categorizations by cytogenetic abnormalities. Prognostic implications of chromosome translocation t(11;14)+ are important to inform development of biomarker-targeted therapies such as the B-cell lymphoma-2 (BCL-2) pathway inhibitors. This study aims to evaluate MM treatment (Tx) patterns and outcomes of t(11;14)+ compared with other cytogenetic cohorts in US routine clinical practice. Methods: A retrospective observational cohort study of the Flatiron Health database, which comprises de-identified electronic health record-derived patient (pt)-level data from over 280 community and academic cancer clinics in the US. Pts aged ≥18 years who received a first-line (1L) induction Tx within ≤60 days of MM diagnosis from 1/1/2011 to 1/31/2020, and were not enrolled in a clinical trial were identified at the start of each Tx line (index date) and followed up (f/u) until 1/31/2020. Only cytogenetic results by fluorescence in situ hybridization (FISH) were used to stratify the cohort into: t(11;14)+; standard risk, excluding t(11;14)+ (SR); and high risk, (HR; del 17p, t(4;14), t(14;16), t(14;20), chromosome 1 abnormalities as a proxy for 1q gain; and t(11;14) where it co-occurs). Descriptive analyses of pt characteristics and Tx were conducted. Kaplan-Meier analyses were used to evaluate median time to next treatment (TTNT) and overall survival (OS) with log-rank test for significance. The cohort was stratified by age ≤70/>70 years (yrs) as a proxy for transplant eligibility. Results: Of 10,703 pts with MM in the database, 5982, 3059 and 1595 pts were eligible for 1L, second-line (2L), and third-line (3L) analysis, of which 76%, 84%, and 86%, respectively, had FISH test results before Tx initiation. 14% of pts with FISH test results were t(11;14)+, ~55% SR and ~35% HR. Included pts were predominately male (55%), ~90% treated in the community setting and ~16% African-American. Pts in the 3L cohort were younger at diagnosis with a median age (interquartile range) of 67 (59 ̶ 74) yrs compared with 69 (61 ̶ 76) yrs in both 1L and 2L. The 1L Tx pattern was consistent across cytogenetic cohorts with bortezomib (V), lenalidomide (R), dexamethasone (d) as the most common Tx (>42%). Together, VRd, Rd, Vd, and cyclophosphamide (Cy) in combination with Vd represented ≥90% of 1L Tx (Figure 1). Across 2L cytogenetic cohorts, the most common Tx regimens (≥25%) were VRd and Rd. The use of regimens containing carfilzomib (K) and daratumumab (D) was emerging in 2L: KRd in 8% of t(11;14)+ and HR and 5% in SR; Kd 5% in all groups; DRd in 4% of t(11;14)+ and 3% in SR and HR (Figure 1). 3L Tx pattern was fragmented with different Tx regimens. Rd was the most common 3L Tx option: 9% in t(11;14)+, 10% in SR and 7% in HR (Figure 1). Across all lines of Tx, t(11;14)+ had similar Tx outcomes to SR, and HR had poorest outcomes (Table 1). Pts TTNT shortened as they advanced to later lines of Tx (Table 1). Although TTNT did not differ by age across lines of Tx, OS was superior in pts <70 yrs across all 3 cytogenetic risk cohorts, especially in 1L where transplant in those ≤70 yrs vs >70 yrs at diagnosis was 44% vs 11% for t(11;14)+, 47% vs 10% for SR and 49% vs 9% for HR. Conclusions: This study identified cytogenetic subgroups across 1L to 3L in a predominately community setting in the US. MM t(11;14)+ pts had similar 1L and 2L Tx patterns to SR and HR. Across all lines of Tx, the outcomes of t(11;14)+ and SR pts were comparable and better than HR pts. TTNT was reduced as pts advanced to later lines of Tx. Pts continuing to 3L Tx were younger at diagnosis, but there was not a clear-cut standard of care. While TTNT did not differ by age across lines of Tx, OS was superior in pts <70 yrs across all 3 cytogenetic risk cohorts. This study sets the benchmark for novel treatment options, such as BCL-2 pathway inhibitors, primarily wherever available biomarker-driven therapy is considered appropriate. Disclosures Atrash: Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria; BMS, Jansen oncology, Sanofi: Speakers Bureau; Amgen, GSK, Karyopharm.: Research Funding. Flahavan:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Roche Products Ltd.: Current Employment. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Karve:AbbVie: Current Employment, Current equity holder in publicly-traded company. Hong:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Jirau-Lucca:Genentech, Inc.: Current Employment; AbbVie: Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company; Celgene: Divested equity in a private or publicly-traded company in the past 24 months. Nixon:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Ailawadhi:Takeda: Honoraria; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding; Amgen: Research Funding; Celgene: Honoraria; Janssen: Research Funding.

scholarly journals Treatment Patterns, Adverse Events, and Economic Burden in a Privately Insured Population of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3557-3557 ◽  
Author(s):  
Shaum Kabadi ◽  
Ravi K Goyal ◽  
Saurabh P Nagar ◽  
James A Kaye ◽  
Keith L Davis ◽  
...  
Keyword(s):  
Health Care ◽  
Adverse Events ◽  
Systemic Therapy ◽  
Research Funding ◽  
The United States ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
The Us ◽  
Privately Insured

Abstract Introduction: Contemporary data describing treatment patterns, adverse events (AEs) and outcomes in CLL patients in clinical practice is lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health care resource use (HCRU), and costs in patients with newly diagnosed CLL. Methods: Using a nationally representative population of privately insured patients in the US, adult patients with CLL were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to 4 lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. Results: Of all patients meeting the selection criteria (n=7,639; median age, 66 years), 18% (n=1,379) received a systemic therapy during study follow-up. The most common systemic therapy regimens, regardless of therapy line, were bendamustine/rituximab (BR) (32%), rituximab monotherapy (24% [including maintenance]), ibrutinib monotherapy (15%), and fludarabine/cyclophosphamide/ rituximab (FCR) (14%). Of these, BR was the most common LOT-1 regimen (28.1%), while ibrutinib was the most common regimen in LOT-2 (20.8%) and in LOT-3 (25.5%). Use of idelalisib was limited to 1.6% of all patients receiving systemic therapy; however, an increasing trend was observed as patients moved from first to fourth LOT (<1% in LOT-1, 3.1% in LOT-2, 4.7% in LOT-3, and 8.6% in LOT-4). AEs identified during the most common treatments for CLL are presented by treatment regimen in Table 1. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD=$15,757) and $5,185 (SD=$9,935), respectively. Figure 1 depicts mean monthly costs by care setting and number of AEs, among all patients. Mean (SD) monthly all-cause costs during the post-index date follow-up were $905 ($1,865) among those with no AEs, $1,655 ($5,364) among those with 1-2 AEs, $2,883 ($8,483) among those with 3-5 AEs, and $6,032 ($13,290) among those with ≥6 AEs. Conclusions: This population-based study yielded recent real-world evidence on treatment patterns, AEs, HCRU, and costs in patients enrolled in health plans in the US. Immunochemotherapy, particularly BR, remained the preferred frontline therapy for CLL, whereas ibrutinib was the preferred therapy in LOT-2 and LOT-3, during the study period. This study demonstrates that the AE burden associated with current treatment alternatives for CLL is substantial, and the management of AEs occurring during treatments may have a significant impact on the overall health care costs. Disclosures Kabadi: AstraZeneca: Employment. Goyal:RTI Health Solutions: Employment, Research Funding. Nagar:RTI Health Solutions: Employment, Research Funding. Kaye:RTI Health Solutions: Employment, Research Funding. Davis:RTI Health Solutions: Employment, Research Funding. Mato:Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Sunesis: Honoraria, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Honoraria; Acerta: Research Funding; Prime Oncology: Speakers Bureau; Regeneron: Research Funding.

scholarly journals Comparison of Denosumab Versus Intravenous (IV) Bisphosphonate Use for Hypercalcemia in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-16
Author(s):  
Matthew M Lei ◽  
Erica Tavares ◽  
Uvette Lou ◽  
Evan Buzgo ◽  
Noopur S. Raje ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Dysfunction ◽  
Board Of Directors ◽  
Research Funding ◽  
Additional Dose ◽  
Newly Diagnosed ◽  
Median Dose ◽  
Publicly Traded ◽  
Advisory Committees ◽  
The Past

Background Hypercalcemia (HC) is a frequent complication of multiple myeloma (MM) occurring in 20-30% of patients. This is often associated with renal dysfunction and both features are important myeloma defining events resulting in significant morbidity and mortality. Denosumab, a fully human monoclonal antibody that inhibits RANKL, has been evaluated in the prevention of skeletal related events in patients with newly diagnosed MM, as well as the treatment of bisphosphonate-refractory HC of malignancy (HCM). Cases of denosumab for HCM in MM patients with renal dysfunction have been described. Both denosumab and IV bisphosphonates (IVB) represent treatment options for HC in MM. We describe a comparison of patients with MM with HC who received denosumab vs IVBs. Methods We retrospectively identified patients age ≥18 with a diagnosis of MM with HC (corrected serum calcium level [CSC] &gt;10.5 mg/dL). Patients were included if they received either denosumab or IVB (zoledronic acid [ZA] or pamidronate), between April 2016 and June 2020. The primary endpoint was complete response (CR), defined as normalization of CSC to less than 10.5 mg/dL. Secondary endpoints included HC relapse (CSC &gt;10.5 mg/dL) and safety. Hypocalcemia was graded per CTCAE v5. Acute kidney injury (AKI) was defined using KGIDO criteria. Patients were followed-up for 56 days. Bivariate analyses were performed. Results A total of 40 patients were included with 18 in the denosumab group and 22 in the IVB group, of whom 15 (68%) received ZA and 7 (32%) received pamidronate. Baseline characteristics are described in Table 1. Patients with newly diagnosed MM composed 33% and 55% of the denosumab and IVB groups, respectively. All patients in the denosumab group received 120 mg except one who received 60 mg, while in the IVB group, dose reductions occurred in 5/15 patients who received ZA (median dose, 4 mg; range, 3.3-4) and 4/7 patients who received pamidronate (median dose, 60 mg; range, 30-90). Most patients received HC treatment as an inpatient (58% inpatient vs. 42% outpatient). A minority of patients had received IVBs in the past 90 days. The mean CSC was 12.5 mg/dL (standard deviation [SD], 1.40) and 13.3 mg/dL (SD, 2.39) in the denosumab and IVB groups, respectively. Baseline serum creatinine (SCr) was higher and creatinine clearance (CrCl) was lower in the denosumab group (median SCr, 2.06 vs. 1.24 mg/dL, p=0.048; median CrCl, 33 vs. 48 mL/min, p=0.048). The CR rate by day 3-4 was 92% and 94% in the denosumab and IVB groups, respectively (p=NS). HC relapse occurred in 2 (12%) and 6 (29%) patients in the denosumab and IVB groups, respectively (p=0.257). Incidence of grade 1 hypocalcemia was similar between groups; however, incidence of grade ≥2 hypocalcemia was higher in the denosumab group. Incidence of new AKI was 28% (5/18) in the denosumab group 23% (5/22) in the IVB group (p=0.71). No patients in the denosumab group received an additional dose of denosumab within 14 days of initial dose. Three patients in the IVB group received an additional dose of an IVB within 14 days of initial dose. One patient, who was in the denosumab group, had refractory hypercalcemia and had not achieved CR at day 56. Conclusions We describe our experience with denosumab and IVB for the management of HC in patients with MM. The CR rate at 3-4 days was similar with either agent in our MM only population that was not bisphosphonate refractory. A higher incidence of grade 2 hypocalcemia was noted in the denosumab group. Conclusions on renal safety are limited by the small sample size and that patients in the denosumab group had a higher SCr on presentation. Denosumab and IVB represent acceptable agents for the management of HC in MM patients with further investigation necessary in those with renal dysfunction. Disclosures Lei: Fresenius Kabi USA: Consultancy; Trapelo Health: Consultancy; Bluebird Bio: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Clovis Oncology: Current equity holder in publicly-traded company; Blueprint Medicines: Divested equity in a private or publicly-traded company in the past 24 months. Lou:Fresenius Kabi USA: Consultancy. Raje:Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy. Yee:Karyopharm: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. We describe the use of denosumab for hypercalcemia of malignancy in a multiple myeloma only patient population that is not bisphosphonate refractory. The use of denosumab for these patients was part of normal clinical practice in adherence to institutional policies and guidelines.

scholarly journals Real World Evidence in Relapsed/Refractory Classical Hodgkin Lymphoma Patients Who Are Ineligible for Stem Cell Transplant in the United States (US)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2268-2268
Author(s):  
Joseph Feliciano ◽  
Nate Way ◽  
Gerald Engley ◽  
Nilanjan Ghosh
Keyword(s):  
Real World ◽  
Systemic Therapy ◽  
Research Funding ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Cell Transplant ◽  
Real World Evidence ◽  
The Us ◽  
Line Of Therapy

Abstract Introduction: Treatment of relapsed or refractory classical Hodgkin lymphoma (R/R cHL) in patients considered ineligible for stem cell transplant (SCT) in the United States (US) has evolved since 2011. It is important to understand the current treatment landscape and the outcomes associated with current standards of care as new treatment options have been introduced. This analysis provides recent real-world evidence on patient characteristics, treatment patterns, and outcomes in R/R cHL patients in the US who are initially considered ineligible for SCT and are treated with or without brentuximab vedotin (BV). Methods: Hematologists and oncologists (N=205) from the US retrospectively identified patients diagnosed with R/R cHL who received at least two lines of therapy and received their most recent line of therapy between January 2014 and May 2018. The physicians were responsible for abstracting data and completing response forms for variables of interest. The current analysis focused on patients who were considered ineligible for SCT by their physician: descriptive statistics on patient demographics/clinical characteristics, treatment patterns, and outcomes by line of therapy; bivariate analyses (chi-square) comparing treatment modalities by line of therapy. Results: Physicians retrospectively identified 297 patients that they considered ineligible for SCT. Mean (SD) age at initial cHL diagnosis was 53.0 (18.5), most patients were male (69.4%) and Caucasian (61.3%). The most common cHL subtype at diagnosis was nodular sclerosis HL (40.4%), and patients had either Stage I/II (45.8%) or Stage III/IV (54.2%) cHL at initial diagnosis. Median follow-up time for the cohort included here was 15.96 months from initiation of 1L treatment. The majority of the cohort (N = 297) received systemic therapy alone (84.5%) compared to those who received systemic therapy in combination with radiation therapy (RT) (15.5%) in 1L. 1L systemic regimens included regimens that contained ABVD alone or ABVD in combination with other regimens (69.4%). Of those who used ABVD alone or in combination with another regimen (N = 206), 24.8% used a PET adapted approach and deescalated to AVD (N = 51) and 11% escalated to be BEACOPP (N = 18). Other systemic regimens included AVD (10.1%), BEACOPP (7.4%) and ICE (5.7 %). The majority of patients achieved a complete response (CR) or partial remission (PR) after 1L therapy (41.4%, 38% respectively) while 34.1% (N = 61) failed to achieve remission or progressed while on therapy. The most common systemic regimens in 2L (N = 293) were BV monotherapy or in combination with bendamustine (34.6%), salvage regimens [including ICE, DHAP, ESHAP or gemcitabine based combinations] (33%), re-challenge with a previous 1L regimen (19.5%), and PD-1 inhibitors (10.8%). Very few patients received systemic therapy in combination with RT (6.7%) in 2L.The most common systemic regimens used in 3L (N = 21) for the selected cohort of patients not eligible for SCT were BV monotherapy (28.6%) and PD-1 inhibitors (33.3%). Median (range) number of cycles in 2L and 3L was four (1-18) and two (1-14), respectively. Treatment outcomes were variable for patients in 2L and 3L. In 2L, 27.6% achieved a CR, 25.6% achieved a PR, while 24.2% and 15.8% were refractory or progressed on treatment. There were no CRs reported in 3L (N = 21). 26 patients died in 2L and 3L combined. Conclusion/Summary: Given the rapid evolution of therapies used to treat R/R cHL, these findings fill a crucial data gap in real-world evidence on patient characteristics, treatment patterns, and outcomes of patients deemed SCT ineligible in the US. Disclosures Feliciano: Seattle Genetics: Employment. Way:Kantar Health: Employment; Seattle Genetics: Research Funding. Engley:Seattle Genetics: Employment. Ghosh:Juno: Consultancy, Research Funding; SGN: Consultancy, Research Funding, Speakers Bureau; PCYC: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy; Spectrum: Consultancy; Gilead: Consultancy, Speakers Bureau; Pharmacyclics, an Abbvie Company: Consultancy, Research Funding, Speakers Bureau; Genentech: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Abbvie: Consultancy, Speakers Bureau; Forty seven Inc: Research Funding; TG Therapeutics: Honoraria, Research Funding.

scholarly journals Treatment Patterns Among Newly Diagnosed Multiple Myeloma Patients in the United States Veteran Population (2010-2015)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5952-5952
Author(s):  
Kejal Parikh ◽  
Shivani Pandya ◽  
Safiya Abouzaid ◽  
Onur Baser ◽  
Lin Xie ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Treatment Patterns ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Chemotherapy Agent ◽  
The Us ◽  
Equity Ownership

Abstract Background: Despite a relatively higher incidence in the veteran population, there are few real-world claims-based analyses to describe Multiple Myeloma (MM) treatment patterns among this patient population (Landgren O, Blood, 2006). This study aimed to assess treatment patterns among newly diagnosed MM (ndMM) patients using the US Veteran Health Administration (VHA) data. Methods: This retrospective study identified adult patients with ≥2 claims for MM (ICD-9-CM code: 203.0x) 30 days apart and ≥1 treatment during identification period (1OCT2011-31MAR2015) from the VHA dataset. The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless patients died within 6 months (follow up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant (ASCT)), and no evidence of ASCT in the follow up period. A subsequent COT (COT2) was defined as the earliest occurrence of: the addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or a dose increase from maintenance to relapse therapy. Dexamethasone/prednisone[d] which were assumed to be included regardless of whether or not they were observed during the study period did not impact the ongoing COT. Treatment patterns during the follow-up period were initially examined among patients treated with novel (lenalidomide [R] and/or bortezomib [V] with or without chemotherapy agents) and non-novel therapies (≥1 chemotherapy agent, steroid monotherapy) and then compared among those initiating Rd and Vd. Time to next treatment (TTNT) was defined as the duration from initiation of COT1 plus any gaps before COT2. Kaplan Meier and Cox regression analyses were performed to evaluate TTNT and assess the impact of various predictors on TTNT among patients initiating Rd and Vd. Results: Of 1,183 patients that met the inclusion criteria, 55.4% (n=655) were treated with novel therapies and 44.6% (n=528) with non-novel therapies. Among patients treated with novel therapy, the majority initiated Rd (47.8%; n=313) as COT1 followed by Vd (31.2%; n=204), Vd with cyclophosphamide (11.5%; n=75), RVd (6.6%; n=43), Vd with a chemotherapy agent (2.4%; n=16) and Rd with a chemotherapy agent (0.6%; n=4).Rd initiators were significantly older (75.1 vs 70.6 years, p=0.0002) and a higher percentage was white (69.7% vs 47.0%; p<0.0001) than Vd treated patients. While the Charlson Comorbidities Index score did not differ between the two groups (3.6 vs 4.0, p=0.0583), a significantly higher percentage of patients treated with Vd had some comorbidities including hepatitis and renal disease. Among patients with laboratory tests, patients treated initially with Vd had lower hemoglobin (10.8 vs 11.4 g/dl, p=0.0012) and higher serum creatinine (2.3 vs 1.4 mg/dl, p<0.0001) during the pre-index period. The overall average treatment duration in COT1 was significantly longer among patients treated with Rd vs Vd (10.9 vs 7.0 months, p<0.0001). Among patients who were still on active COT1, the mean duration in COT1 was longer among patients treated with Rd than Vd (18.7 vs 13.3 months, p=0.0061). A significantly higher percentage of patients treated with Vd progressed to COT2 (52.5%, vs 26.2% p<0.0001) as compared to Rd. Among patients who progressed to COT2, those treated with Vd had a shorter TTNT compared to Rd (Mean: 9.3 vs 12.8 months, p=0.0049). After adjusting for baseline demographic and clinical factors using Cox regression, TTNT remained significantly shorter for Vd vs those treated with Rd (HR: 2.67, 95% CI: 1.9-3.7, p <0.0001). Conclusion: Slightly over half of MM patients in the US Veteran population were treated with a regimen containing novel therapies; Rd and Vd were the most commonly observed among these. Patients treated initially with Vd had a significantly shorter TTNT compared to those treated with Rd. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on Vd. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Baser:Celgene: Research Funding. Xie:Celgene: Research Funding. Patel:Celgene: Consultancy.

scholarly journals Real-World Clinical Management of Patients with Congenital Hemophilia and Inhibitors: Interim Analysis of the FEIBA Global Outcome Study (FEIBA GO)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Cedric Hermans ◽  
Claude Négrier ◽  
Pål A Holme ◽  
Carmen Escuriola ◽  
Ana R Cid ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Interim Analysis ◽  
Research Funding ◽  
Hemophilia A ◽  
Outcome Study ◽  
Publicly Traded ◽  
On Demand ◽  
The Past

Introduction and Objective: Development of inhibitory antibodies is a major complication of factor replacement therapy in patients with congenital hemophilia A or B. The FEIBA Global Outcome study (FEIBA GO) assessed the long-term safety and real-world effectiveness of activated prothrombin complex concentrate (aPCC; Baxalta US Inc, a Takeda company, Lexington, MA, USA) as prophylaxis or on-demand treatment in patients with congenital hemophilia A or B with inhibitors (PwHI) across different clinical settings. Methods: FEIBA GO (EUPAS6691) is a post-authorization, prospective, observational, multicenter cohort study. Male PwHI diagnosed before study entry and prescribed treatment with aPCC as part of routine clinical practice were followed over 4 years; treatment regimens were prescribed at the physician's discretion. Ethics approval and patient consent were obtained. These data report on an interim analysis (data cutoff, May 16, 2019) on the annualized bleeding rate (ABR) calculated per patient-year of follow-up and aPCC consumption in patients receiving aPCC prophylaxis. Results: Enrollment was started on September 3, 2014 and completed on December 31, 2017. Fifty-one enrolled PwHI have received aPCC prophylaxis (n=37) or on-demand (n=14) treatment from 26 sites in 11 countries (hemophilia A: n=50, hemophilia B: n=1; median [range] age at baseline: 17 [2-71] years). As of May 2019, mean±SD (median, range) ABR was 7.2±8.2 (5.7, 0-30) per patient-year for the 14 patients with ≥2 to &lt;4 years' study follow-up (mean±SD: 3.0±0.6 years). In the 3 patients with ≥4 years of study follow-up (mean±SD: 4.0±0.03 years), mean±SD (median, range) ABR was 14.7±25.3 (0.2, 0-44) per patient-year. Patients received a variety of prophylaxis regimens; data on dosages per infusion and number of weekly infusions administered are provided in the Table. Conclusions: This interim analysis describes the real-world use and effectiveness of aPCC prophylaxis and supports previous data on the prevention of bleeding events in PwHI. The data also highlight the variety of dosing regimens reflecting the real-world use of aPCC prophylaxis in clinical practice. Although patient numbers were small, these data suggest that increased weekly doses are used in patients with more severe bleeding phenotypes. Figure 1 Disclosures Hermans: Kedrion:Speakers Bureau;Octapharma:Consultancy, Speakers Bureau;Roche:Consultancy, Speakers Bureau;Pfizer:Consultancy, Research Funding, Speakers Bureau;Novo Nordisk:Consultancy, Speakers Bureau;LFB:Consultancy, Speakers Bureau;Shire, a Takeda company:Consultancy, Research Funding, Speakers Bureau;Sobi:Consultancy, Research Funding, Speakers Bureau;Bayer:Consultancy, Research Funding, Speakers Bureau;EAHAD:Other;WFH:Other;CSL Behring:Consultancy, Speakers Bureau;CAF-DCF:Consultancy, Speakers Bureau;Biogen:Consultancy, Speakers Bureau.Négrier:CSL Behring, Octapharma, Shire/Takeda, Sobi:Research Funding;CSL, F. Hoffmann-La Roche Ltd, Sobi:Other: Travel support;Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark:Consultancy.Holme:Sobi:Honoraria, Research Funding;Bayer:Honoraria, Research Funding;CSL Behring:Honoraria;Novo Nordisk:Honoraria;Octapharma:Research Funding;Pfizer:Honoraria, Research Funding;Shire, a Takeda company:Honoraria, Research Funding.Escuriola:Grifols:Honoraria;CSL Behring:Consultancy, Honoraria, Research Funding;Biotest:Honoraria, Research Funding;Biomarin:Honoraria;Bayer:Honoraria;Kedrion:Honoraria;Shire, a Takeda company:Honoraria;Octapharma:Consultancy, Honoraria, Research Funding;Novo Nordisk:Consultancy, Honoraria;Roche:Honoraria;Sobi:Honoraria, Research Funding.Cid:Roche:Consultancy, Honoraria;Sobi:Consultancy, Honoraria;Novo Nordisk:Honoraria;Shire, a Takeda company:Honoraria.Kemenyash:Takeda Pharmaceutical International AG:Current Employment, Current equity holder in publicly-traded company.Botha:Takeda Pharmaceutical International AG:Current Employment, Current equity holder in publicly-traded company.Cano-Garcia:Sanofi Genzyme:Current Employment, Current equity holder in publicly-traded company;Shire, a Takeda company:Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months.Windyga:Sanofi:Honoraria, Research Funding;Alexion:Honoraria, Research Funding;Alnylam:Honoraria, Research Funding;Baxalta/Shire, a Takeda company:Honoraria, Research Funding;Bayer:Honoraria, Research Funding;Siemens:Honoraria, Research Funding;Sobi:Honoraria, Research Funding;Werfen:Honoraria, Research Funding;CSL Behring:Honoraria, Research Funding;Ferring Pharmaceuticals:Honoraria, Research Funding;Novo Nordisk:Honoraria, Research Funding;Octapharma:Honoraria, Research Funding;Rigel Pharmaceuticals:Honoraria, Research Funding;Roche:Honoraria, Research Funding.

scholarly journals Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4657-4657
Author(s):  
Kristin M. Zimmerman Savill ◽  
Ajeet Gajra ◽  
Kwanza Price ◽  
Jonathan K. Kish ◽  
Cherrishe Brown-Bickerstaff ◽  
...  
Keyword(s):  
Data Collection ◽  
Board Of Directors ◽  
Systemic Therapy ◽  
Research Funding ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
Independent Contractor ◽  
Advisory Committees

Abstract Introduction: Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, dysplasia in ≥ 1 cell line, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia. Treatment goals for MDS classified as lower-risk (LR-MDS) include transfusion independence, improvement in hemoglobin (Hb) levels, and maintenance of or improvement in quality of life. Erythropoiesis-stimulating agents (ESAs) are the first-line (1L) treatment for anemia in most patients with LR-MDS lacking del(5q), but a proportion of patients do not respond to ESA treatment, or experience progression of anemia despite ESA treatment. The objective of this real-world analysis was to describe patient characteristics, treatment patterns (including ESA use), and outcomes in patients with LR-MDS. Methods: A retrospective, observational, US multisite, cohort study was conducted among adult patients initially diagnosed with LR-MDS between January 1, 2017 and June 25, 2020. Eligible patients had ≥ 1 year of follow-up after diagnosis (unless the patient died during this time) and did not receive luspatercept or any MDS treatment as part of a randomized, controlled trial. Community oncologists abstracted data from medical records, and descriptive statistics were used to summarize patient characteristics, treatment patterns, and outcomes. Data presented are from an interim analysis of an ongoing study; the last date of data collection for this analysis was July 6, 2021. Results: Among 125 eligible patients with LR-MDS, median follow-up time was 16 months, and 83% of patients were still alive at the time of data collection. In the 8 weeks prior to diagnosis, 54% of patients did not receive any red blood cell (RBC) or platelet transfusions, while 42% and 4% had low or moderate transfusion burden, respectively. Overall, 75% of patients were negative for del(5q), and 80% of patients were negative for ring sideroblasts (RS). At diagnosis of LR-MDS, serum erythropoietin levels were &lt; 200 U/L in 49% of patients, ≥ 200 U/L in 25%, and unknown in 26%. In terms of disease management, 35% of patients did not receive any systemic therapy or transfusions, 14% received RBC and/or platelet transfusions, but no systemic therapy for MDS, and 50% were reported to have received ≤ 2 lines of systemic therapy following LR-MDS diagnosis (Table). Of the 42% of patients who received an ESA, 70% received an ESA for MDS as a single agent (SA) only, 15% as combination therapy only, and 8% as both SA and combination therapy. A further 8% received SA ESA followed by a non-ESA-based regimen. Among 45 patients who received SA ESA as 1L treatment, 18% went on to receive a hypomethylating agent (HMA) or immunomodulatory imide drug as an SA, or ESA combined with HMA or a granulocyte or granulocyte-macrophage colony-stimulating factor (G-CSF/GM-CSF) in a subsequent line. Among patients who received an ESA, 72% were still on ESA-based therapy at the time of data collection. Abstracting physicians reported that 17% of patients who received an ESA failed ESA treatment. Among these patients, physicians' determination of ESA failure was based on the National Comprehensive Cancer Network guidelines/International Working Group 2006 response criteria for 78% of patients, and on physicians' own clinical judgement for 22%. At data collection, ESA was still being administered to 22% of patients considered to have failed ESA treatment. Finally, 34% of those who received an ESA also received RBC transfusion(s) during ESA-based treatment and therefore were not transfusion independent for the entire duration of ESA-based treatment (Table). Conclusions: Results from this real-world cohort study indicate that over a third of patients with LR-MDS have been managed using watchful waiting only, with no systemic treatment or transfusions received; among those patients who received treatment, most received an ESA. Nearly one-fifth of patients in this study treated with an ESA were considered to have failed ESA treatment by abstracting physicians, though this proportion is likely to be higher with extended follow-up; 2 of 9 patients who failed ESA treatment were still receiving an ESA. Further research including longer follow-up is warranted to understand how patients with LR-MDS respond to different treatment regimens. Figure 1 Figure 1. Disclosures Zimmerman Savill: Cardinal Health: Current Employment; Roche/Genentech: Ended employment in the past 24 months. Gajra: Cardinal Health: Current Employment, Current equity holder in publicly-traded company. Price: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kish: Cardinal Health: Current Employment, Current equity holder in publicly-traded company, Research Funding. Brown-Bickerstaff: Cardinal Health: Current Employment. Falkenstein: Cardinal Health: Current Employment. Miller: Cardinal Health: Current Employment. Laney: Cardinal Health: Current Employment. Mukherjee: Acceleron: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research/Independent Contractor, Research Funding; McGraw Hill: Honoraria, Other: Editor of Hematology Oncology Board Review (ongoing); Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research/Independent Contractor, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; AAMDS in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria; Eusa Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Teaching and Speaking; Jazz Pharmaceuticals: Research Funding; Bristol-Myers Squibb Co.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BioPharm: Consultancy; Partnership for Health Analytic Research: Honoraria; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Treatment Patterns and Outcomes Among Patients with Relapsed/Refractory Follicular Lymphoma Treated in Routine Clinical Practice in the US with Three or More Lines of Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4080-4080
Author(s):  
Jamie T. Ta ◽  
Stella Arndorfer ◽  
Cristina Julian ◽  
Mei Wu ◽  
Dominic Lai ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Real World ◽  
Treatment Initiation ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
The Past ◽  
Community Oncology ◽  
The Us ◽  
Early Progression

Abstract Background: Follicular lymphoma (FL) is an indolent, yet incurable disease, and patients often require several lines of therapy throughout their lifetime (Batlevi et al. Blood Cancer J 2020); however, there are limited real-world data available regarding the treatment of a contemporary cohort of patients with relapsed/refractory (R/R) FL. The objective of this study was to assess real-world treatment patterns and outcomes among patients receiving third- and later-line (3L+) therapies for FL in the US. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. During the study period, de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. We selected patients aged ≥18 years with an initial FL diagnosis between January 2011 and January 2021, who had received at least 3 lines of therapy for FL (follow-up ended March 2021). Exclusion criteria included: evidence of clinical trial participation during the study period, high-grade (3b) FL at diagnosis, transformation to an aggressive lymphoma any time before 3L FL treatment, or other anticancer therapies or stem cell transplant 12 months before first-line (1L) FL treatment. Patient demographic and clinical characteristics were assessed using descriptive statistics. Treatment patterns and time to next anti-lymphoma treatment or death (TTNTD) were reported. Median TTNTD was estimated using Kaplan-Meier methods. Results: Of 2,990 patients receiving treatment for FL during the study period, 157 patients who received at least 3 lines of therapy for FL were included. Median age at time of 3L FL treatment initiation was 70 years, and 48.4% (n=76) of patients were male. At initial FL diagnosis, 79.6% (n=125) had low-grade (1-2) FL, 78.3% (n=123) had advanced stage (III/IV) FL, and 68.6% (n=48) of the 70 patients with available Follicular Lymphoma International Prognostic Index (FLIPI) scores had high-risk FLIPI (≥3). Overall, 68.2% of patients had evidence suggestive of early progression of disease within 24 months of 1L FL treatment. The majority of patients were treated at community oncology practices (n=140 [89.2%]). Median time to 3L treatment initiation from diagnosis was 35.6 months, and median follow-up after 3L treatment was 15.4 months. Fifty-two (33.1%) patients received a subsequent fourth-line therapy. The most common 3L treatment regimens received were rituximab (R) monotherapy (n=32 [20.4%]), R plus bendamustine (n=26 [16.6%]), R plus lenalidomide (n=18 [11.5%]), obinutuzumab monotherapy (n=14 [8.9%]), and idelalisib (n=13 [8.3%]; Table). Median TTNTD after 3L treatment was 14.1 months (95% confidence interval: 10-23.6; Figure). Conclusions: Our study provides an update on the heterogeneous treatment landscape for R/R FL in the US for patients receiving 3L+ therapy in real-world clinical practice, the majority of whom were treated in community oncology practices. Many patients requiring 3L+ FL treatment had clinical characteristics predictive of poor prognosis, as evidenced by the high proportion of patients who had evidence of early progression and high-risk FLIPI at diagnosis. Treatment outcomes following 3L therapy remain poor, and approximately one-third of patients required additional treatment beyond 3L. Limitations of this analysis include those inherent to real-world observational databases and the relatively short follow-up of patients with indolent FL in the Flatiron Health database, particularly following 3L FL treatment. Future studies with additional follow-up are warranted. Nevertheless, these findings highlight the ongoing unmet need for novel, effective treatments in this setting in order to improve patient outcomes. Figure 1 Figure 1. Disclosures Ta: Genentech, Inc.: Current Employment. Arndorfer: Genesis Research: Consultancy, Current Employment. Julian: Genentech, Inc.: Current Employment, Current holder of stock options in a privately-held company. Wu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Lai: Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Shapouri: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.

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