scholarly journals Real-World Practice Patterns with Carfilzomib in Patients with Relapsed and Refractory Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5765-5765
Author(s):  
R. Donald Harvey ◽  
Ze Cong ◽  
Winifred Werther ◽  
Jan L. Lethen ◽  
Sagar Lonial
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Dose Escalation ◽  
Real World ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Patient Demographics ◽  
The Third ◽  
Starting Dose ◽  
The Us

Abstract Background: Single-agent carfilzomib (CFZ), a selective proteasome inhibitor, received accelerated approval in the US (July 2012) for the treatment of patients with relapsed and refractory multiple myeloma (MM). The approved dosing schedule is a 2–10 minute intravenous infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. The starting dose is 20 mg/m2 during cycle 1; if well tolerated, it should be escalated to a target dose of 27 mg/m2 during cycles 2 and beyond, as CFZ dose-escalation may be associated with improved responses. To date, adherence to this schedule in a real-world setting has not been evaluated. We present results from a retrospective analysis that assessed the frequency of CFZ dose escalation in routine clinical practice and its association with patient demographics, clinical characteristics, concomitant medications, and duration of therapy (DOT). Methods: This study was a retrospective analysis of clinical practice data with CFZ in the US. Data were obtained from the OSCER electronic medical record (EMR) database, which collates information on patient demographics, clinical characteristics, and treatment from multiple hematology/oncology practices. Patients were included if they were diagnosed after January 1, 2005 and received CFZ between July 20, 2012 and March 1, 2014 after previous exposure to bortezomib and an immunomodulatory agent. In the primary analysis, patients were classified as escalators if they received an increased dose of CFZ within 29 days (start of cycle 2) of initiation and non-escalators if they did not receive an increased dose of CFZ within 29 days. The Kaplan-Meier method with death as a competing risk and end of follow-up as right censored was used to compare DOT between escalators and non-escalators. To test the sensitivity of the analysis to the criteria for classifying patients by presence of dose escalation, calculations were repeated with patients classified as escalators if they received an increased dose of CFZ by the third cycle of treatment and non-escalators if they did not receive an increased dose of CFZ by the third cycle. Results: A total of 281 patients in the OSCER EMR database met inclusion criteria. Data regarding dose escalation within 29 days or 3 cycles of starting treatment with CFZ was obtained for 244 and 153 patients, respectively; the majority (75%) were treated in practices in the southern region of the US. Fifty-five percent of patients received an increased dose of CFZ within 29 days of initiating treatment and 80% received an increased dose by the third cycle. Demographics (age and sex) and clinical characteristics (Eastern Cooperative Oncology Group performance status and presence of renal failure or chronic kidney disease) were similar between escalators and non-escalators (p>0.08). Although a greater proportion of non-escalators received granulocyte-colony stimulating factors (G-CSF) compared with escalators (<29 days: 16% vs 4%, respectively; <3 cycles: 19% vs 10%), a significant proportion of patients who did not receive G-CSF were also non-escalators (<29 days: 42%; <3 cycles: 18%). The median DOT was significantly higher in patients who were escalated within 29 days compared with patients who were not (160 vs 114 days, respectively; p=0.02; Fig. 1). Patients who were escalated within 3 cycles had a trend for increased median DOT compared to those who were not (184 vs 163 days, respectively; p=0.07; Fig. 2). Among patients who did not receive G-CSF, escalators had a longer DOT compared with non-escalators, consistent with results in the overall population. Conclusion: A non-trivial proportion of patients (20%) who received CFZ were not dose-escalated by the third cycle of treatment. The demographics and clinical characteristics examined did not appear to distinguish escalators from non-escalators, and concomitant use of G-CSF did not fully explain why some patients were not escalated. As escalators had a longer DOT compared with non-escalators, there may be consequent differences in disease progression outcomes between escalators and non-escalators. Further investigation of demographics and disease characteristics (e.g. high-risk disease) in escalators and non-escalators is needed to understand the reasons behind the practice of continuing the starting dose, but not escalating, in those patients who do not receive target doses of CFZ, and what effect this practice has on disease progression outcomes. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Harvey: Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Research Funding; Acetylon: Research Funding; Amgen: Research Funding. Cong:Onyx Pharmaceuticals: Employment. Werther:Onyx Pharmaceuticals: Employment, Equity Ownership. Lethen:Amgen. Inc.: Employment. Lonial:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

scholarly journals Clinical Course of High-Risk Multiple Myeloma Patients in Korea: A Multicenter Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-14
Author(s):  
Kihyun Kim ◽  
Jin Seok Kim ◽  
Sung-Soo Yoon ◽  
Dok-Hyun Yoon ◽  
HyeonSeok Eom ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Real World ◽  
Research Funding ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Clinical Course ◽  
Working Party ◽  
Cytogenetic Abnormality ◽  
Cytogenetic Abnormalities

Introduction: Increased understanding of the pathophysiology of multiple myeloma (MM) and the introduction of new drugs has led to considerable survival improvements in recent years. The International Myeloma Working Group consensus recently updated the definition for high-risk MM based on cytogenetic abnormalities. Moreover, the recent introduction of new therapeutic agents and the revision of insurance reimbursement policies have changed the clinical characteristics of MM patients in Korea. Yet, current epidemiology and the clinical characteristics of MM patients in Korea have not been fully investigated. Therefore, we aimed to understand the characteristics and management of Korean MM patients in a real-world setting by analyzing patients with high-risk cytogenetic abnormalities in the Korean Myeloma Registry. Methods: This is a retrospective observational study using the Korean Myeloma Registry, the web-based multicenter patient registry system established by the Korean Multiple Myeloma Working Party. Patients who are newly diagnosed with MM from 2010 to 2017 with at least one high-risk cytogenetic abnormality [t(4;14), t(14;16), or del(17p)] were included. Primarily, patients were classified by cytogenetic abnormality into three groups: Group 1, t(4;14) or t(14;16); Group 2, del(17p); and Group 3, t(4;14)/del(17p) or t(14;16)/del(17p). These patients were also stratified by the revised International Scoring System (R-ISS) and transplantation history for detailed analysis. We also used the number of cytogenetic abnormalities in an explanatory analysis; in this case, we included gain(1q). Progression-free survival (PFS) and overall survival (OS) were estimated, and the Hazard Ratio with the log-rank test was used for statistical comparison. Results: 391 out of 2170 MM patients from seven hospitals were identified as high-risk patients (men, 49.6%; median age, 63 years old). Median PFS for all patients was 18.9 months (95% CI 17.27-20.33), and the median OS was 44.6 months (95% CI 36.5-60.1). PFS (P&lt;0.001) and OS (P=0.012) between the cytogenetic abnormality groups were significantly different after stratification by transplant history. Patients with t(4;14)/del(17p) or t(14;16)/del(17p) amongst transplant recipients showed the worst outcome, with median PFS 15.5 (95% CI 8.7-20.5) months and median OS 35.6 (95% CI 14.9-N/A) months. Without stratification, there were no significant between-group differences in PFS and OS. OS was also significantly different between cytogenetic abnormality groups stratified by the revised International Staging System (R-ISS) (P=0.003). The lowest median OS durations were 16.9 months (95% CI 6.5-33.6) for del(17p) with R-ISS III, and 21.7 months (95% CI 9.3-N/A) for t(4;14)/del(17p) or t(14;16)/del(17p) with R-ISS III. Patients with higher R-ISS staging in the presence of del(17p) showed worse survival outcomes. Finally, PFS and OS were significantly inversely correlated with the number of cytogenetic abnormalities (P&lt;0.001). Conclusion: In real-world data from the Korean Myeloma Registry, we were able to observe the association of poor prognosis of MM patients with the number of cytogenetic abnormalities (PFS and OS) and R-ISS (OS). Moreover, we were also able to find the association of cytogenetic abnormality del(17p) and poor prognosis in MM patients. Lastly, we believe that this study provides the characteristics and management of MM patients needed to understand the real-world clinical course of high-risk MM patients in South Korea. Disclosures Kim: Amgen, BMS, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Yoon:Novartis: Consultancy, Honoraria; Janssen: Consultancy; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; YuhanPharma: Research Funding; Kyowahako Kirin: Research Funding; Amgen: Consultancy, Honoraria. Yoon:Celltrion: Honoraria; Samyang: Research Funding; Amgen, Chongkundang, Celgene, Astrazeneca: Consultancy. Lee:AMGEN: Current Employment.

Abstract 220: Early Assessment of Real-world Utilization and Dosing of Sacubitril/Valsartan in the US

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Chun-Lan Chang ◽  
Xue Song ◽  
Tina Willson ◽  
Carol Duffy
Keyword(s):  
Real World ◽  
Maintenance Dose ◽  
Healthcare Providers ◽  
Dose Titration ◽  
Dose Increase ◽  
Early Assessment ◽  
Reduced Ejection Fraction ◽  
Starting Dose ◽  
The Us ◽  
Medicare Patients

Background: Based on the PARADIGM-HF trial, sacubitril/valsartan was approved for the treatment of patients with heart failure and reduced ejection fraction. This study provides an early view of its real-world utilization and dosing in the US before recent guideline updates. Methods: Adult patients with >=1 sacubitril/valsartan claim in 7/7/2015 - 3/31/2016 were selected from a large national claims dataset; their 1st sacubitril/valsartan claim was the index date. Data was required for >=24 months pre-index and >=3 months post-index. Dose at index and the maximum dose achieved post-index were obtained. Dose up-titration, defined as 1st appearance of a sacubitril/valsartan claim with a dose increase from the index strength, and the time to 1st dose increase were reported. Results: Among 981 qualified patients with a mean follow-up of 185 (SD ±81) days, 25% commenced sacubitril/valsartan on the suggested prescribing information (PI) starting dose of 49/51 mg b.i.d.; 58% started on 24/26 mg b.i.d.; 4% started on an even lower dose, and 13% indexed at the target maintenance dose of 97/103 b.i.d.. The target maintenance dose of 97/103 mg b.i.d. was achieved in 30% of patients. For those 856 patients indexing on <=49/51/ mg b.i.d., 58% had no dose up-titration post-index; 31% took >4 weeks to have up-titration initiated and 11% initiated up-titration within 4 weeks. Only 25% of Medicare patients compared to 35% of Commercial patients achieved the target dose of 97/103mg b.i.d.. (Table 1) Conclusion: Most patients commenced sacubitril/valsartan at lower doses than recommended in the PI and were poorly optimized, with the majority of patients having no upward dose titration. Approximately 13% actually indexed at the target maintenance dose. The reasons for these findings need further exploration. Healthcare providers should consider following the appropriate starting doses, with timely dose adjustment of sacubitril/valsartan as recommended in the PI to ensure patients receive the full clinical benefit of this medication as demonstrated in the PARADIGM-HF trial.

Real-world treatment patterns and outcomes of triple-exposed multiple myeloma patients treated in community oncology practices in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18727-e18727
Author(s):  
Robert Smith ◽  
Mei Xue ◽  
Natalie Dorrow ◽  
Prateesh Varughese ◽  
Cosima Hogea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Real World ◽  
Proteasome Inhibitors ◽  
Office Visit ◽  
The United States ◽  
Subsequent Treatment ◽  
Treatment Patterns ◽  
Duration Of Therapy ◽  
The Us

e18727 Background: Treatment for multiple myeloma (MM) over the past decade has significantly improved survival. In particular, 3 drug classes have altered the treatment paradigm for MM patients: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies (anti-CD38s). Despite these advances, the majority of patients with MM will become refractory to PIs, IMiDs, and anti-CD38s, and limited evidence indicates these patients have poor outcomes. A retrospective study in the US showed that 275 patients treated at 14 academic institutions with prior exposure to a PI, IMiD, and anti-CD38 had median overall survival of 9.2 months. The aim of this study was to evaluate real-world treatment patterns and outcomes (duration of therapy and overall survival) of patients who had been treated with a PI, IMiD, and anti-CD38 in community practices in the US. Methods: This retrospective observational study was conducted using the Integra Connect (IC) database. The IC database includes electronic health data from structured and unstructured fields from 12 community practices on the East and West Coast of the US. Adult patients with ≥2 ICD-9/ICD-10 codes for MM on at least 2 separate dates, who received MM treatment between Jan 1, 2016, and Dec 31, 2019, with treatment history that included at least one PI, one IMiD, and one anti-CD38 (triple exposed), and initiated a subsequent line of therapy (s-LOT) after becoming triple exposed, were included. Duration of length of s-LOT was defined as number of days from start of s-LOT to last-day supply of s-LOT. Overall survival was defined as the length of time from start of s-LOT through death or the date of the last office visit. Results: A total of 501 patients were included in this analysis. The median age of patients was 64.9 years; 50% were male; 50% had commercial insurance. 82.8% of patients had ECOG 0 or 1 at diagnosis and had received a median of 3 prior lines of therapy (LOTs) before initiating s-LOT. Prior to initiating s-LOT, 91% had been exposed to bortezomib, 81% to carfilzomib, 94% to lenalidomide, 82% to pomalidomide, and 100% to daratumumab. In s-LOT, 95% received treatment that included same drug or same drug class (30% received bortezomib, 48% carfilzomib, 31% lenalidomide, 47% pomalidomide, and 31% daratumumab). The median duration of s-LOT was 78 days and median survival was 10.3 months (308 days) from initiation of s-LOT. Conclusions: For triple-class exposed patients, there is a lack of consensus on the most efficacious approach to subsequent treatment. The present study shows a significant amount of retreatment with previously used agents or classes among these patients with short duration of therapy and poor survival. As has been previously noted, new strategies and agents targeting novel aspects of MM are needed to improve outcomes for these patients. Disclosures: This study (213286) was sponsored by GlaxoSmithKline.

scholarly journals Individualized Dosing of Hydroxyurea for Children with Sickle Cell Anemia Using a Population Pharmacokinetic-Based Model: The TREAT Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3652-3652 ◽  
Author(s):  
Patrick T. McGann ◽  
Min Dong ◽  
Anu Marahatta ◽  
Thad A. Howard ◽  
Tomoyuki Mizuno ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Research Funding ◽  
Sampling Strategy ◽  
Sparse Sampling ◽  
Primary Objective ◽  
Time Points ◽  
Individualized Dosing ◽  
Starting Dose ◽  
Population Pk ◽  
Sampling Approach

Abstract Background: Hydroxyurea is the primary disease modifying therapy for patients with sickle cell anemia (SCA). The clinical and laboratory benefits of hydroxyurea are the greatest when escalated to the maximum tolerated dose (MTD). The process of dose escalation to MTD requires expertise and can be tedious, often taking 6-12 months to titrate to the optimal dose. In addition, due in part to inter-patient variability in hydroxyurea pharmacokinetics (PK), the MTD varies among patients with a range of 15-35 mg/kg/day. We utilized a population PK model in combination with Bayesian estimation and a sparse sampling strategy, to individualize dosing of children starting hydroxyurea treatment. Methods: The Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154) is a prospective study of hydroxyurea for children with SCA. The primary objective is to develop and evaluate a population PK-based model to predict hydroxyurea MTD through an individualized dosing strategy. A sparse sampling approach was developed to allow practical sampling from young children with SCA. The sampling strategy includes administering a single oral 20 mg/kg dose followed by collection of small quantities of blood (~100uL) at three post-dosing time points (15-20 minutes, 50-60 minutes, and ~3 hours). Baseline labs (including liver and renal function) are typically collected by venipuncture, while the other two samples are drawn by fingerstick or heelstick. Plasma hydroxyurea concentrations are measured using HPLC using an internal standard of methylurea. Using the population PK model with Bayesian estimation and hydroxyurea concentrations measured at the three specified time points, hydroxyurea exposure is estimated using specialized therapeutic drug monitoring software (MWPharm, Mediware, Prague, Czech Republic). Using the area under the curve (AUC0-inf) estimated by the model, we calculate a starting dose that is predicted to achieve an AUC of 115 ug*h/mL, which was the mean AUC value at MTD for a large cohort of children from a previous study (Dong M et al. Br J Clin Pharmacol 2016). The primary objective is to select a starting dose that is close to actual MTD, to reduce the time to maximum therapeutic effect and need for dose modifications before achieving MTD. Results: From December 2014 through June 2016, 20 children taking taking hydroxyurea for the first time were enrolled in TREAT. Seventeen of the 20 participants had all 3 post-treatment PK samples collected and processed to allow calculation of an individualized PK-based dose, while 3 had difficulties in sampling or processing that prevented a safe PK-guided dose recommendation. These 3 participants were started at the standard hydroxyurea dose of 20 mg/kg/day. The Table summarizes baseline characteristics for the initial study population, notable for a very young starting age with 13/20 (65%) less than two years of age. Twelve children with PK-based initial dosing have been treated with hydroxyurea for at least six months. Despite the young starting age, after six months of hydroxyurea, children have documented increases in total Hb (1.4+/-1.9 g/dL), HbF (11.3+/-6.4%), and MCV (15+/-8 fL) and decreases in absolute reticulocyte count (-217+/-128 x 109/L) and absolute neutrophil count (-1.0+/-1.9 x 109/L). In 9 of 12 participants, the PK-guided initial dose remained the best clinical dose at six months without significant dose changes except for minor adjustments for weight. Two patients required a single dose escalation due to inadequate marrow suppression, while one required a dose hold and decrease due to neutropenia during and following a viral infection. Conclusions: These data demonstrate that a sparse sampling approach, requiring only 3 blood samples over 3 hours, is able to accurately estimate hydroxyurea exposure in children with SCA. Hydroxyurea exposure, as defined by AUC, was similar with this sparse sampling approach as previous studies that relied upon a more standard and prolonged PK sampling approach. This population PK model is then able to predict a safe starting dose of hydroxyurea that approximates the actual MTD, with clinically significant improvements in laboratory parameters following six months of therapy. This individualized PK-guided dosing regimen should simplify hydroxyurea dosing and reduce the time interval to reach MTD and maximal clinical benefits. Table Table. Disclosures Kalfa: Baxter/Baxalta/Shire: Research Funding. Quinn:Silver Lake Research Corporation: Consultancy; Amgen: Research Funding; Eli Lilly: Research Funding. Ware:Nova Laboratories: Consultancy; Addmedica: Research Funding; Global Blood Therapeutics: Consultancy; Bayer Pharmaceuticals: Consultancy; Biomedomics: Research Funding; Bristol Myers Squibb: Research Funding.

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