scholarly journals Real-World Use of FLT3-TKIs in R/R FLT3-Mutated AML in the United States

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
David L. Grinblatt ◽  
Bhavik J. Pandya ◽  
Wei Han ◽  
Loretta Sullivan ◽  
Qi Feng ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Board Of Directors ◽  
Real World ◽  
Treatment Duration ◽  
The United States ◽  
Treatment Patterns ◽  
Prescription Data ◽  
Concomitant Chemotherapy ◽  
Advisory Committees ◽  
Specialty Pharmacy

Background: Targeted inhibition of the FLT3 tyrosine kinase is a treatment strategy for patients with relapsed or refractory, FLT3 mutation-positive acute myeloid leukemia (R/R FLT3mut+ AML). While the multikinase inhibitors, sorafenib and midostaurin, were not approved specifically for R/R AML, they are used off-label as treatment. Since FDA approval on 11/28/2018, gilteritinib has become the first globally approved targeted therapy for the treatment of R/R FLT3mut+ AML in adults. This study aims to understand the treatment landscape for R/R FLT3mut+ AML patients following the introduction of a new therapeutic agent. Aim/Objective: To describe the characteristics and treatment patterns of patients initiating FLT3 tyrosine kinase inhibitors (TKIs) for R/R FLT3mut+ AML in the real-world setting. Methods: This US-based retrospective cohort study was conducted using two separate closed-claims databases (MarketScan, 1/1/2007-2/29/2020; IQVIA, 1/1/2006-4/30/2020) and a specialty-pharmacy claims database (ProMetrics, 12/6/2018-3/12/2020). Patients ≥18 years of age, with an AML diagnosis and newly initiated FLT3-TKI (ie, gilteritinib, midostaurin, or sorafenib) therapy for R/R diagnosis or episode ("R/R AML") on or after gilteritinib market availability were eligible for inclusion. Patients were indexed on the first newly initiated FLT3-TKI for R/R AML observed on or after 12/1/2018. Patients' baseline clinical and demographic characteristics, AML-related treatments preceding FLT3-TKI initiation for R/R AML, and concomitant therapies (defined as any AML-related treatment overlapping with FLT3-TKI use after R/R AML) were identified. Because individual patients could have received more than one FLT3-TKI during the study period, treatment sequencing was analyzed by FLT3-TKI-containing regimens. Given the larger sample size available within the ProMetrics Specialty Pharmacy database, gilteritinib dose patterns and treatment duration were analyzed using de-identified dispensed prescription data from a separate gilteritinib-only cohort for greater precision. Descriptive statistics were used to evaluate all study outcomes, except for treatment duration, which was estimated using Kaplan-Meier life table analysis. Results: A total of 52 and 51 patients initiating FLT3-TKIs for R/R AML were identified in the MarketScan and IQVIA databases, respectively. The mean age of patients was 53.1 (MarketScan) and 52.3 years (IQVIA); patients had a mean ± SD Quan-Charlson Comorbidity Index of 3.6 ± 2.4 (MarketScan) and 3.7 ± 2.2 (IQVIA). Most patients treated with FLT3-TKIs for R/R AML during the study period were first initiated on gilteritinib (MarketScan: n=35 [67.3%], IQVIA: n=36 [70.6%]); sorafenib was the second most common FLT3-TKI (MarketScan: n=9 [17.3%], IQVIA: n=8 [15.7%]), followed by midostaurin (MarketScan: n=8 [15.4%], IQVIA: n=7 [13.7%]). During the study period, 61 and 55 FLT3-TKI-containing regimens among 52 and 51 R/R AML patients were identified across the MarketScan and IQVIA databases, respectively. Most FLT3-TKI-containing regimens for R/R AML included gilteritinib (MarketScan: n=43 [70.5%], IQVIA: n=38 [69.1%]). Prior exposure to other FLT3-TKIs for new onset and/or R/R AML indications was observed in up to 63% of gilteritinib-, 56% of sorafenib-, and 13% of midostaurin-containing regimens (Table). Following onset of R/R AML, gilteritinib was given without concomitant chemotherapy in 47% (Marketscan: 20/43) to 55% (IQVIA: 21/38) of gilteritinib regimens; in a smaller sample of sorafenib regimens, sorafenib was given without concomitant chemotherapy in up to 56% (IQVIA: 5/9) of regimens. Of 748 patients identified in the ProMetrics database with gilteritinib claims, 714 (95%) patients were initiated on a 120-mg daily dose, with less than 5% (n=34) incurring a downward dosage titration. The median treatment duration was 150 days (95% CI: 129-172 days). Conclusions: Among FLT3-TKI-containing regimens initiated for R/R AML after gilteritinib market approval, close to 70% included gilteritinib, an agent approved for R/R FLT3mut+ AML. Sample sizes for midostaurin- and sorafenib-containing regimens limited characterization of treatment patterns. Gilteritinib was given without concomitant chemotherapy in approximately 50% of regimens prescribed; the dose and treatment durations were similar to those previously reported by the ADMIRAL trial. Disclosures Grinblatt: Astellas: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau. Pandya:Astellas Pharma, Inc.: Current Employment. Sullivan:Astellas Pharma: Current Employment. Feng:Astellas: Current Employment. Hedlund:Astellas: Current Employment.

scholarly journals Streamline - Retrospective Cohort Study of Relapsed or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML): Real-World Treatment, Testing Patterns, and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-31
Author(s):  
Amer M. Zeidan ◽  
Adrienne M. Gilligan ◽  
Santosh Gautam ◽  
David L. Grinblatt ◽  
Dina Elsouda ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Board Of Directors ◽  
Real World ◽  
Targeted Therapies ◽  
Research Funding ◽  
Treatment Patterns ◽  
Advisory Committees ◽  
Mutation Status ◽  
Flt3 Mutation ◽  
Flt3 Mutations

Introduction: The past decade in AML research has led to increased emphasis on disease-related mutations and associated targeted therapies. FMS-like tyrosine kinase 3 (FLT3) mutations (FLT3+) are found in about 30% of AML patients and confer a poorer prognosis. Also, the availability of targeted therapies increases the value of testing for FLT3+ AML. A paucity of data exists regarding the real-world FLT3 testing rates in AML patients in both the newly diagnosed and R/R settings. As the treatment landscape for patients with R/R FLT3+ AML expands, it is important to understand how utilization of these therapies and trends in FLT3 testing impact patient outcomes in real-world settings. These updated results examined FLT3 testing trends, treatment patterns, and overall survival (OS) in patients with R/R FLT3+ AML. Patients were grouped based on the FDA approval of the second-generation FLT3 inhibitor gilteritinib (pre-gilteritinib approval vs. post-gilteritinib approval). Methods: This ongoing (01/01/2015-4/17/2020) retrospective study uses electronic medical record data of US patients from a network of 400+ oncology practices maintained in the Definitive Oncology Dataset, including practices affiliated with CancerLinQ. Eligible adult (≥18 years) patients who had a confirmed diagnosis of AML, FLT3+ status, and had ≥1 R/R event between 01/01/2015 and 02/20/2020 were included. FLT3 testing trends included testing performed at initial diagnosis, re-testing performed in the R/R setting, and changes in FLT3 mutation status. Treatment patterns included all systemic anticancer therapies received (including supportive care) for R/R FLT3+ AML. OS was measured from the first R/R event; patients without evidence of death were censored at the last observed visit. Kaplan-Meier analysis was applied to evaluate differences in OS by subsequent hematopoietic stem cell transplant (HSCT) status. Results: Data from 175 patients (50.9% male, n=89) with R/R FLT3+ AML were evaluated (n=124 pre-gilteritinib; n=51 post-gilteritinib). Most patients were White (72.0%; n=126) with a median age of 62 years (range: 20-86) at first R/R event. Median length of follow-up was limited for the post-gilteritinib cohort (9.2 months vs. 15.0 months for pre-gilteritinib, P<0.001). Patients tested for FLT3 mutations at initial AML diagnosis increased from 84.7% (n=105/124) in the pre-gilteritinib cohort to 98.0% (n=50/51) in the post-gilteritinib cohort, and the rates of re-testing increased from 29.5% (n=31/105) to 46.0% (n=23/50) across the two cohorts (Figure 1). After the first R/R event, 18.9% (n=33/175) reported changes in their FLT3 mutation status. Seventy-four different treatment combinations were utilized at the first R/R event. Use of FLT3 tyrosine kinase inhibitors (TKIs), either alone or in combination with chemotherapy, increased from 30.6% (n=38/124) in the pre-gilteritinib cohort to 49.0% (n=25/51) in the post-gilteritinib cohort (Table 1). In the pre-gilteritinib cohort midostaurin (52.6%, n=20/38) and sorafenib (32.4%, n=13/38) were the most commonly prescribed FLT3 TKIs. In the post-gilteritinib cohort, the most common FLT3 TKI was gilteritinib (52.0%, n=13/25). Median OS (95% CI) across all patients at the first R/R event was 13.4 (9.0-17.6) months in the pre-gilteritinib cohort and 12.9 (7.0, NA) months in the post-gilteritinib cohort. Median OS was significantly shorter among patients that did not receive HSCT among all patients and the subset of treated patients (P<0.05 for both values). Median OS for patients with no HSCT was 3.9 months longer in the post-gilteritinib cohort versus the pre-gilteritinib cohort (Table 2). Conclusion: An increase in FLT3 TKI use (both monotherapy and in combination) and a decrease in high-intensity chemotherapy was observed across the two cohorts. In the 18-month post approval period, FLT3 TKI use increased 60% with gilteritinib accounting for more than half of FLT3 TKIs used in the R/R setting. FLT3 re-testing increased by 55% in the R/R setting between the two cohorts; however, re-testing is suboptimal and there is a need to re-test as patients progress. Among pre- and post-treated patients that did not receive HSCT, there was an improvement in OS by almost 4 months, possibly due to increased use of targeted FLT3 TKIs. With recent approval of these targeted therapies, it will be important to continue to monitor FLT3 testing, treatment patterns, and clinical outcomes. Disclosures Zeidan: Celgene / BMS: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Ionis: Consultancy, Honoraria; BeyondSpring: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; CCITLA: Other; Astex: Research Funding; Cardinal Health: Consultancy, Honoraria; Trovagene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Leukemia and Lymphoma Society: Other; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Taiho: Consultancy, Honoraria; Aprea: Research Funding; ADC Therapeutics: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; MedImmune/Astrazeneca: Research Funding; Acceleron: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Cardiff Oncology: Consultancy, Honoraria, Other. Gilligan:ConcertAI: Current Employment. Grinblatt:Astellas: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau. Elsouda:Astellas: Current Employment. Sullivan:Astellas Pharma: Current Employment. Pandya:Astellas Pharma, Inc.: Current Employment.

scholarly journals Emicizumab-Kxwh for Previously Untreated Patients with Haemophilia: The Conversation Begins

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2409-2409
Author(s):  
Tiffany Lin Lucas ◽  
Shveta Gupta ◽  
Joanna A. Davis ◽  
Fernando F. Corrales-Medina
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Hemophilia A ◽  
The United States ◽  
Haemophilia A ◽  
Advisory Committees ◽  
Inhibitor Development ◽  
Increased Risk ◽  
Prophylaxis Therapy

Introduction: With the Federal Drug and Administration approval of the use of emicizumab from birth to adulthood, clinicians will now grapple with when to choose and offer emicizumab for routine prophylaxis, especially in previously untreated patients (PUPs). Given the overall limited real-world reported data and experience using emicizumab in PUPs, we created and administered a survey to medical providers in the United States who care for paediatric patients with haemophilia to investigate real-world practice strategies and treatment selection for PUPs. Methods: After review and endorsement by the Haemostasis and Thrombosis Research Society (HTRS), the survey was electronically distributed by e-mail to all providers included in the HTRS core member list. The survey was also sent to those providers included in a list of Haemophilia Treatment Centre (HTC) physicians (with duplicate emails reconciled). Providers needed to self-identify as ones that treat pediatric patients to be included. The survey was developed as a tiered survey with questions presented to each recipient based on their prior responses. Results: Seventy-seven completed surveys were included and analysed. All participants were active providers at a comprehensive HTC and the majority (93.4%) were practicing at an academically affiliated site. In terms of characteristics of those that answered the survey, forty-eight percent of responders reported that 1-20% of their patients had expressed interest in emicizumab. 46% of participants (34/74) reported that they would personally consider emicizumab as their prophylaxis recommendation for the majority (>50%) of their hemophilia A patients without inhibitors. 57% (44/76) reported that 1-10% of their non-inhibitor hemophilia A patients were already prescribed emicizumab prophylaxis. Each participant was then asked about his or her consideration of emicizumab as prophylaxis therapy for a 2 month old PUP. Just over the majority were unsure or said no to this consideration (51.3%) and their concerns were lack of information on safety and efficacy in this young age group and increased risk for inhibitor development. If the 2 month old PUP had a high risk of inhibitor, the majority of providers who initially were hesitant to start emicizumab prophylaxis would remain so. Of note, those providers went on to be asked if the patient had gone on to complete 50 exposure days without inhibitor development, they would then become more likely to initiate emicizumab prophylaxis therapy. Use of concurrent factor replacement was posed to all participants and there were varied responses. Discussion: Overall, our results reflect a widespread practice variation and a not yet well-standardized or defined approach for the use of emicizumab in PUPs with haemophilia A. In this survey, patient preference and individual bleeding risk were the top reasons for which a provider would consider using switching to emicizumab prophylaxis in both severe and mild/moderate haemophilia A patients. This pattern of practice reflects the current era of individualized medicine. Overall, our findings reinforce the need for more studies to investigate the outcomes of a combined treatment approach with FVIII concentrates and emicizumab focusing in the potential benefit of this approach in decreasing the risk for inhibitor development PUPs. Clinicians also feel the need for further data to help clarifying the safety of emicizumab in this population. Figure Disclosures Gupta: Novartis: Honoraria, Speakers Bureau; CSL Behring: Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Davis:Sanofi: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Shire: Consultancy; Spark Therapeutics: Consultancy. Corrales-Medina:Kedrion: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Epidemiology of PNH and Real-World Treatment Patterns Following an Incident PNH Diagnosis in the US

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3407-3407 ◽  
Author(s):  
Jessica J Jalbert ◽  
Umesh Chaudhari ◽  
Haixin Zhang ◽  
Jonathan Weyne ◽  
Jamile M. Shammo
Keyword(s):  
Incidence Rate ◽  
Real World ◽  
Treatment Duration ◽  
Research Funding ◽  
The United States ◽  
Treatment Patterns ◽  
Employment Equity ◽  
Equity Ownership ◽  
Procedure Codes ◽  
Rbc Transfusion

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening blood disease. While PNH is known to be a rare disease, the incidence and prevalence of the condition has been described only in a few small studies. In addition, while the International PNH registry is a rich source of data on real-world PNH patients globally, it is not possible to estimate the incidence and prevalence of PNH directly from the registry. As complement inhibitors are becoming the standard of care for PNH treatment, we also sought to explore how patients are managed following an incident PNH diagnosis. The objective of this study was to estimate the incidence and prevalence of PNH and to describe real-world treatment patterns among patients newly diagnosed with PNH in the United States (US). Methods: We conducted a retrospective cohort study using Truven US MarketScan Commercial/Medicare data (1 Jan 2015 to 30 June 2018), an employer-sponsored insurance claims database including annually approximately 30 million insured patients and their dependents' complete longitudinal records of inpatient services, outpatient services, and prescription drug claims covered under a variety of fee-for-service and capitated health plans. While these data are considered nationally representative of Americans with employer-provided health insurance, data come mainly from large employers. To estimate prevalence, we identified patients with ≥ 1 PNH diagnosis (ICD10: D59.5) among persons continually enrolled in the databases in 2017. To estimate incidence, we required ≥1-year of baseline enrolment and no PNH diagnosis or eculizumab exposure, identified using national drug codes [NDC] or procedure codes for drug administration, during the baseline period. Person-time accrued post-baseline until PNH diagnosis, end of study period, or disenrollment. We stratified incidence and prevalence estimates by age and sex and described patients with incident PNH in terms of demographics, comorbidities, and past-year healthcare resource utilization. Using Kaplan-Meier estimators, we estimated incidence of eculizumab initiation, timing of initiation, treatment duration, and risk of discontinuation/treatment holiday (>42 days between eculizumab exposures [i.e. 14-day exposure period + 28-day grace period between infusions], the equivalent of missing 2 infusions assuming a bi-weekly infusion schedule for eculizumab) following the incident PNH diagnosis. While accounting for censoring, we also investigated patterns of red blood cell (RBC) transfusions, identified using procedure codes, in terms of incidence and timing of first transfusion following an incident PNH diagnosis. Results: The prevalence of PNH varied little between 2016 and 2017, from 12 to 13 per 1,000,000. The incidence rate over the study period was 5.7 per 1,000,000 person-years, representing 257 incident PNH cases. The incidence rate of PNH increased with age and was similar across sex. At diagnosis, mean age was 50.0 years (standard deviation [SD]: 18.6), 3.1% (8/257) were less than 18 years, 52.1% were women, 19.5% had a past-year diagnosis of aplastic anemia, 8.2% had a past-year diagnosis of myelodysplastic syndrome, 14.0% had a past-year RBC transfusion, and 31.5% had been hospitalized in the past-year. Over a mean follow-up time of 385.6 days (SD: 253.2), 10.3% (95% confidence interval [CI]: 6.3-14.1%) of patients initiated eculizumab on average 60.5 days (SD: 55.9) from PNH diagnosis. At 1 year, about one third of patients discontinued eculizumab or had taken a treatment holiday; average treatment duration was 328.2 days (SD:245.4). Cumulative incidence of RBC transfusions at 6 months and 1 year was 14.6% (10.1-18.9%) and 17.4% (12.2-22.3%), respectively. On average, the first RBC transfusion occurred within 63.6 days (SD: 114.4) of an incident PNH diagnosis. Conclusions: In routine clinical practice, only a minority of patients recently diagnosed with PNH are initiated on eculizumab. Among PNH patients treated with eculizumab, less than 70% remain on treatment after 1 year. Findings must be interpreted in the context of limitations including lack of information on clone size, symptom burden, measures of disease activity, or bone marrow failure state which may affect treatment course. Future studies should explore factors affecting eculizumab initiation and persistence on treatment. Disclosures Jalbert: Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Chaudhari:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhang:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Weyne:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Shammo:Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; Onconova: Research Funding; Apellis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Speakers Bureau; Astex Pharma: Research Funding; Novartis: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; CTI Pharma: Research Funding.

scholarly journals Real-World Data on the Use of rFIXFc in Subjects With Hemophilia B for Up to 3.7 Years Demonstrates Improved Bleed Control and Adherence With Reduced Treatment Burden

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2493-2493 ◽  
Author(s):  
Amy Shapiro ◽  
Ateefa Chaudhury ◽  
Nisha Jain ◽  
Elisa Tsao ◽  
Chris Barnowski ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
The United States ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Real World Data ◽  
Advisory Committees ◽  
Dosing Interval ◽  
Before And After

Abstract Introduction: Recombinant factor IX Fc fusion protein (rFIXFc) was the first extended half-life FIX product approved in the United States to treat children and adults with hemophilia B. Long-term data from clinical trials have demonstrated the safety and efficacy of rFIXFc as well as an extended dosing interval (once weekly or every 10‒14 days based on individual needs); however, real-world data are limited (Wang et al. Haemophilia, 2018; Buckley et al. AMCP NEXUS, 2015). We therefore performed a retrospective chart review to further understand the clinical experience and outcomes associated with real-world treatment of hemophilia B with rFIXFc. Methods: This retrospective chart review is being conducted at 6 sites across different regions of the United States and aims to include 70 patient charts. Data entry for 43 patient charts has been completed to date (cutoff: June 29, 2018). Data collection is ongoing. Inclusion criteria were diagnosis of hemophilia B and receipt of rFIXFc for ≥6 months. Subjects with other coagulation disorders or any record of positive FIX inhibitor titers were excluded. De-identified subject-level data were transcribed onto anonymous electronic case report forms. Endpoints included changes in FIX therapy dosing interval, factor consumption, bleed control, and patient adherence before and after rFIXFc initiation. Descriptive statistics were used to summarize the results. Results: For the 43 charts available for analysis, the duration of follow-up receiving rFIXFc ranged from 0.5 to 3.7 years. Of these, 58% of subjects (25/43) were >18 years of age, 77% (33/43) were of white race, and 51% (22/43) had severe hemophilia B (Table 1). The most common genotype was missense, occurring in 63% of subjects (27/43). Among subjects with comorbidity, 37% reported hemophilic arthropathy (16/43) and 28% had hepatitis C (12/43). All 22 subjects with severe hemophilia B were treated with rFIXFc prophylactically compared with 9/15 moderate and 3/6 mild cases. From the data collected thus far, 94% of prophylaxis subjects were on a dosing interval of weekly or longer (every 7 days, n=20; every 10 days, n=3; and every 14 days, n=9). The total weekly dose before and after switching to rFIXFc prophylaxis were available for 20 subjects. Of the 12 adults (9 severe, 2 moderate, and 1 mild), the median weekly factor consumption decreased from 111 IU/kg to 52.5 IU/kg. A similar pattern was observed for subjects who were 12-18 years of age (n=4). For subjects <12 years of age (n=4), 2 had reduced weekly consumption after switching to rFIXFc, whereas 2 (on plasma-derived product pre-rFIXFc) had an increase in weekly consumption. The annualized bleeding rates (ABRs), annualized spontaneous bleeding rates (AsBRs), and annualized joint bleeding rates (AjBRs) were available for 17 subjects treated with prophylaxis regimens pre- and post-rFIXFc (Table 2). Of these subjects, 11 had severe, 5 had moderate, and 1 had mild hemophilia B. Among 11 subjects with severe hemophilia B, median (interquartile range) ABRs decreased from 8.2 (4.4‒11.5) to 2.3 (0.6‒10.2), AsBR from 1.2 (0‒9.7) to 0.3 (0‒8.7), and AjBR from 2.3 (1.4‒8.2) to 0.7 (0‒6.9) before and after rFIXFc treatment. Subjects with moderate disease had a similar pattern (Table 2). The most common reason for switching to rFIXFc was to reduce the burden associated with therapy (21/43, 49%). No rationale for switching was documented in 40% (17/43) of subjects, and 7% (3/43) switched due to lack of efficacy with previous treatment. The other reasons, including difficult venous access, lack of adherence, and failure to reach desired trough were mentioned by <5% of subjects. No subject reported adherence issues while on rFIXFc. Conclusions: This real-world study of rFIXFc demonstrates improved bleed control, reduced overall consumption, and reduced frequency of injection for subjects with moderate and severe hemophilia B. The data also show that rFIXFc provides an opportunity to tailor dosing and improve adherence. These results echo the findings of the pivotal trials and add to the pool of evidence supporting rFIXFc in the treatment of hemophilia B. These data also reflect the use of rFIXFc for mild hemophilia patients in the real-world setting. Disclosures Shapiro: Kedrion Biopharma: Consultancy, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ, a Sanofi Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prometic Life Sciences: Consultancy, Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer Healthcare: Other: International Network of Pediatric Hemophilia; BioMarin: Research Funding; Bio Products Laboratory: Consultancy; Octapharma: Research Funding; OPKO: Research Funding; Sangamo Biosciences: Consultancy; Daiichi Sankyo: Research Funding. Chaudhury:Bioverativ, a Sanofi Company: Consultancy, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees. Jain:Bioverativ: Employment. Tsao:Bioverativ: Employment. Barnowski:Bioverativ, a Sanofi Company: Employment. Feng:Bioverativ: Employment. Quon:Shire: Speakers Bureau; Genetech: Consultancy, Speakers Bureau; NovoNordisk: Consultancy, Speakers Bureau; Bayer: Consultancy; Octapharma: Consultancy; Bioverativ, a Sanofi Company: Speakers Bureau.

scholarly journals Real-World Treatment Patterns and Transfusion Burden Among US Patients with Newly Diagnosed Myelodysplastic Syndromes (MDS)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3499-3499
Author(s):  
Sudipto Mukherjee ◽  
S. Lane Slabaugh ◽  
Ronda Copher ◽  
Jonathan Johnson ◽  
Paul Buzinec ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Treatment Duration ◽  
Research Funding ◽  
Index Date ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Median Treatment ◽  
Medical Claims ◽  
Median Treatment Duration

Introduction: Symptomatic anemia transfusion support represents a significant problem for patients with MDS. The principal strategy in managing these patients remains supportive care with erythropoiesis-stimulating agents (ESAs) and red blood cell (RBC) transfusions. However, there is paucity of real-world data regarding patterns of use of ESA and other therapies, and its impact on transfusion needs in these patients early in their clinical course. To address this question, we performed a retrospective claims-based study to characterize treatment patterns and transfusion burden in patients with MDS. Methods: In this retrospective claims analysis of a large national health insurance plan, all patients aged ≥ 18 years with newly diagnosed MDS (≥ 2 medical claims with an International Classification of Diseases, 9th or 10th Revision [ICD-9 or ICD-10] diagnosis codes ≥ 30 days apart) identified between January 2012 and May 2018 were included. Index date was defined as date of first diagnosis. Continuous health plan enrollment for ≥ 6 months pre- and 3 months post-index date was required. RBC transfusion status was evaluated during the 16 weeks prior to first diagnosis as well as 16 weeks prior to and immediately following line of therapy (LOT) 1 and LOT2. Transfusion burden categories were adapted and modified from the proposed International Working Group 2018 revised criteria (Platzbecker U, et al., Blood. 2019;133(10):1096-1107). Categories included transfusion independence (TI), defined as patients receiving no transfusions during the observation period; low (LTB), moderate (MTB), and high transfusion burden (HTB) were defined by patient's having 1-3, 4-7, and ≥ 8 unique dates for a transfusion during the observation periods, respectively. Therapies in each LOT were captured using pharmacy and medical claims data. The end of a LOT was defined after ≥ 60-day gap in therapy, a claim for any new or additional MDS therapy, or patient death; LOT durations are described for non-censored patients. Results: Among the 3,587 patients identified (mean age = 74.9 years, 44.3% female), transfusion burden during 16 weeks prior to index was: 78.8% TI, 19.2% LTB, 1.9% MTB, and 0.2% HTB. Among the 1,935 patients who received LOT1, transfusion burden in the 16 weeks preceding LOT1 was: 57.0% TI, 36.3% LTB, 5.6% MTB, and 1.1% HTB. The top 5 regimens in LOT1 were ESA monotherapy (61.9%), hypomethylating agent (HMA) monotherapy (19.2%), white blood cell growth factor (WBCGF) monotherapy (3.5%), immunomodulators (3.3%), and HMA + ESA (2.7%) (Figure). Of 824 patients who received LOT2, transfusion burden prior to LOT2 was: 49.4% TI, 28.6% LTB, 16.5% MTB, and 5.5% HTB. The top 5 regimens in LOT2 were ESA monotherapy (44.2%), HMA monotherapy (12.1%), HMA + ESA (9.2%), WBCGF + ESA (6.9%), and WBCGF monotherapy (6.4%) (Figure). In LOT1, the median treatment duration for ESA monotherapy was 2.8 months (mean = 5.2 months, standard deviation [SD] = 6.8) whereas in LOT2, the median treatment duration was 2.0 months (mean = 3.7 months, SD = 5.0). Amongst patients receiving ESA monotherapy as LOT2, 90.4% had prior ESA monotherapy as LOT1. In patients treated with HMA monotherapy in LOT1 that also experienced a LOT2, 39.1% moved on to a variety of LOT2 regimens (Table), while in 15.5% ESAs were combined with HMA (Table). Conclusions: Our results show that at the time of diagnosis, 20% of MDS patients were transfusion dependent, but up to 50% require treatment. The high rate of ESA use is likely due to anemia-related symptoms. In those treated with ESA monotherapy, approximately 50% have a LOT1 duration that is &lt; 3 months, and interestingly, the majority of patients restart a second LOT with an ESA as the most common regimen. Additional analyses are necessary to determine whether this indicates a switch in ESA agent, escalation in dose of prior ESA, treatment cycling due to elevated hemoglobin, or other reasons. Considering the short median treatment duration and worsening of transfusion dependency beyond first line, there remains a high unmet need for MDS therapy that more effectively slows the progression of transfusion dependence. Disclosures Mukherjee: Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor. Slabaugh:Celgene Corporation: Employment, Equity Ownership. Copher:Celgene Corporation: Employment. Johnson:Optum: Employment; Celgene Corporation: Consultancy. Buzinec:Optum: Employment. Mearns:Celgene Corporation: Employment.

Treatment Patterns from 2009 to 2015 in Patients with Newly Diagnosed Multiple Myeloma in the United States: A Report from the Connect® MM Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4489-4489 ◽  
Author(s):  
Robert M. Rifkin ◽  
Rafat Abonour ◽  
Brian G.M. Durie ◽  
Cristina J. Gasparetto ◽  
Sundar Jagannath ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
The United States ◽  
Treatment Patterns ◽  
Second Line ◽  
Newly Diagnosed ◽  
First Line ◽  
Advisory Committees ◽  
Frequency Of Use ◽  
The Us

Abstract Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs > 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Real-World Treatment Patterns and Outcomes in Patients with Hemophagocytic Lymphohistiocytosis (HLH) and Other Clinical Conditions Treated with Emapalumab: The Real-HLH Study Design

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4991-4991
Author(s):  
Carl E. Allen ◽  
Jennifer Leiding ◽  
Shanmuganathan Chandrakasan ◽  
Kelly J. Walkovich ◽  
Abiola Oladapo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Clinical Characteristics ◽  
Index Date ◽  
Treatment Patterns ◽  
Patient Identification ◽  
Advisory Committees ◽  
The Real ◽  
The Us ◽  
Clinical Conditions

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by overactivation of the immune system due to systemic release of proinflammatory cytokines, especially of interferon gamma (IFNγ), and persistent activation of macrophages/histiocytes and T cells. Emapalumab, a fully human, anti-IFNγ monoclonal antibody that binds to both free and receptor-bound IFNy, neutralizing its biologic activity, was approved by the Food and Drug Administration (FDA) in 2018 for the treatment of adult and pediatric patients with primary HLH with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. The safety and efficacy of emapalumab was based on results from a pivotal phase 2/3 trial which reported a 63% overall response in patients treated with emapalumab. Since approval, no study has evaluated the use of emapalumab in a larger cohort of patients in the real-world clinical setting. Aim: To assess real-world treatment patterns and outcomes, clinical and demographic characteristics among patients treated with emapalumab. Method: This retrospective, non-interventional, observational medical chart review study will include patients treated across treatment centers in the US with emapalumab in a non-clinical trial setting. The study aims to include more than 100 patients who have been treated with at least one dose of emapalumab between November 20, 2018 and December 31, 2020 (patient identification period). The date that the patient initiates treatment with emapalumab within the patient identification period is defined as the index date. The post-index date is defined as the period from the index date through to the study end date (June 30, 2021), end of data availability for the patient, or date of death, whichever occurs first. Patients will be classified into three groups (i.e. primary HLH, secondary HLH, or non-HLH) based on the information obtained from their charts, the HLH 2004 diagnostic criteria, and adjudication by the REAL-HLH Steering Committee. Results: The primary objective of the study is to describe treatment patterns in patients with HLH treated with emapalumab in a real-world clinical setting, including emapalumab dose, treatment duration, and reasons for initiating or discontinuing treatment. The secondary objectives are to describe demographic and clinical characteristics of patients with HLH treated with emapalumab, and their outcomes. The exploratory objectives include detailing the demographic, clinical characteristics, treatment patterns, and outcomes of patients with non-HLH clinical conditions treated with emapalumab (Table 1). Demographics and clinical characteristics will be analyzed at the time of diagnosis. Treatment patterns and outcomes will be analyzed during the post-index date. Conclusion: The study aims to assess treatment patterns and outcomes, clinical and demographic characteristics among patients treated with emapalumab, a novel IFNγ blocking agent, in real-world clinical settings in the US. Figure 1 Figure 1. Disclosures Allen: Sobi: Consultancy. Leiding: Sobi: Consultancy. Chandrakasan: Sobi: Consultancy. Walkovich: X4 Pharmaceuticals: Other: Local PI for clinical trial involving mavorixafor and patients with neutropenia; Swedish Orphan Biovitrum AB (Sobi): Consultancy, Honoraria; Pharming: Honoraria, Membership on an entity's Board of Directors or advisory committees; Horizon Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oladapo: Sobi: Current Employment. Yee: Sobi: Current Employment. Pednekar: Sobi: Consultancy; PRECISIONheor: Current Employment. Raza: Sobi: Consultancy; PRECISIONheor: Current Employment. Jordan: Sobi: Consultancy.

scholarly journals Treatment Patterns and Outcomes in Patients with Myelodysplastic Syndromes Treated with Hypomethylating Agents: A SEER-Medicare Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3495-3495 ◽  
Author(s):  
Eytan M. Stein ◽  
Dominick Latremouille-Viau ◽  
George J Joseph ◽  
Sherry Shi ◽  
Annie Guerin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Treatment Patterns ◽  
Advisory Committees ◽  
Consulting Services ◽  
Analysis Group ◽  
Unknown Risk ◽  
Study Population ◽  
Equity Ownership

Background: Hypomethylating agents (HMA), azacitidine (AZA) and decitabine (DEC), are the current standard of care in patients with intermediate-2 and high risk myelodysplastic syndromes (MDS) by IPSS prognostic category (higher-risk MDS) based on clinical trials showing increased response rates and overall survival with these agents. However, the outcomes of patients with MDS treated with HMAs have not been comprehensively assessed in real-world practice. This study describes real-world treatment patterns and outcomes among patients with MDS treated with HMAs. Methods: Adult patients with a confirmed MDS diagnosis between 01/2009-12/2015 treated with HMA were identified in the SEER-Medicare database (01/2006-12/2016). The index date was the date of HMA initiation; the first HMA was defined as the index HMA. Patients were required to have Medicare Parts A and B coverage for ≥12 months pre-index and ≥1 month post-index date. Patients with evidence of stem cell transplant (SCT) or acute myeloid leukemia (AML) pre-index, or enrollment in a clinical trial at any time were excluded. Patients meeting the aforementioned criteria formed the study population. An algorithm, based on timing of HMA initiation, timing of diagnosis of pancytopenia (low counts for red blood cells, white blood cells, and platelets), and diagnosis of refractory anemia with excess of blasts (RAEB)-1 and RAEB-2, was developed to categorize patients into specific MDS risk groups using claims data (Figure A). Patients with RAEB-1/2 diagnosis who initiated HMA within 1 month prior to or 4 months post-RAEB diagnosis, or pancytopenia diagnosis within 3 months prior to HMA initiation (regardless of types of MDS diagnosis) were classified into the higher-risk MDS group. Patients with non-RAEB MDS diagnosis and HMA initiation within 1 month prior to or 4 months post-MDS diagnosis were classified into the intermediate-1-risk MDS group; remaining, unclassified patients from the study population were assigned into the unknown-risk MDS group. OS and time to AML transformation (determined by a diagnosis of AML in claims) were assessed for each risk stratum post-index using Kaplan-Meier (KM) analyses. HMA treatment patterns were measured up to 12 months post-index or until the first event among the following: SCT, AML-like intensive chemotherapy use, AML, or end of data/Medicare Parts A and B coverage (follow-up period). Results: A total of 3,046 patients with MDS treated with HMA were included. On average, patients were aged 77.4 years, and 36.8% were female. The majority of patients were classified in the higher-risk MDS group (70.9%), 8.0% in the intermediate-1-risk MDS group, and 21.1% in the unknown-risk MDS group. Median OS was 11.6 months among patients in the higher-risk MDS group, whereas median OS was 18.4 and 19.1 months for patients in the intermediate-1 and unknown-risk MDS groups, respectively (Figure B). Median time to AML transformation was 19.3 months in the higher-risk MDS group, 50.4 months in the intermediate-1-risk MDS group, and was not reached for the unknown-risk MDS group (Figure C). Overall, patients received an average of 5.1 HMA cycles (median = 4.0 cycles) and the majority were complete cycles (90.9%; as indicated per label or, for AZA, also including the commonly used alternative regimens of 5-day 5-0-0 or 7-day with a weekend break 5-2-2). The mean duration of HMA cycles was 32.6 days (median = 28.0 days). As many as 45.3% of patients received &lt;4 cycles, 41.2% eventually discontinued the index HMA, 4.9% switched of HMA, and &lt;1.0% received an AML-like intensive chemotherapy during the follow-up period. Treatment patterns were similar among patients initiated on AZA or DEC (Table). Conclusions: In this US real-world observational study using claims data, risk of death or AML transformation among patients with MDS was high despite HMA treatment, especially for those with higher-risk MDS. More than 70% of patients with MDS treated with HMA were classified with higher-risk MDS. These patients had a poor prognosis, with a median OS shorter than 1 year and a time-to-AML transformation of less than 2 years from HMA initiation. These data highlight the unmet medical needs of patients with MDS treated with HMA, particularly for those in the higher-risk MDS group. Disclosures Stein: Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Latremouille-Viau:Novartis: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Novartis for the conduct of this study. Joseph:Amgen: Equity Ownership; Cigna: Equity Ownership; Pfizer: Equity Ownership; Novartis: Employment, Equity Ownership. Shi:Novartis: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Novartis for the conduct of this study. Guerin:AbbVie: Other: employee of Analysis Group, Inc., which has received consultancy fees from AbbVie. Wu:Novartis: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Novartis for the conduct of this study. Bonifacio:Novartis: Employment. Cao:Novartis: Employment, Equity Ownership.

scholarly journals Real World Prospective Observational Multicenter Trial of Venetoclax-Based Therapy for Patients with AML Reveals Unique Patterns of Patient Selection and Treatment Utilization - Revive Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1246-1246
Author(s):  
Ofir Wolach ◽  
Itai Levi ◽  
David Lavie ◽  
Jonathan Canaani ◽  
Sigal Tavor ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Patient Selection ◽  
Real World ◽  
Research Funding ◽  
Early Death ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Related Factors

Abstract Background: Venetoclax-based combinations were recently approved to treat patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Limited prospective 'real-world' data is available on treatment patterns of venetoclax-based therapy in routine clinical practice. We investigated patterns of patient selection, efficacy, toxicity, patient related outcome and post-remission management in a nationwide multicenter prospective observational trial. Methods: Newly diagnosed pts with AML were enrolled at the time of venetoclax-based therapy initiation from 10 medical centers in Israel. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Results: Between August 12, 2019, and June 17, 2021(data cut) ,127 AML pts were enrolled to receive venetoclax based therapy. Baseline patient and disease characteristics are reported in Table 1. The main reasons for physician's choice of venetoclax-based therapy were age ≥75, comorbidities and ECOG ≥2 (patient related factors) in 76% of cases and adverse disease biology predicting poor response to intensive chemotherapy (disease related factors) in 24% of cases. Most pts started therapy in an inpatient setting, 82 (64.6%) with a median hospitalization duration of 14 days, while 44 pts (34.6%) started therapy as out pts. Pts received a median of 3.8 cycles of therapy (range 1-21). Most pts (97%) received venetoclax in combination with hypomethylating agents. The full dose of 400mg QD after a median ramp-up duration of 3 days was achieved in 88% of the pts. Dose interruptions and dose modifications during follow-up occurred in 59 (46%) and 30 (24%) of pts, respectively. To allow for adequate follow up for response assessment, efficacy analysis was limited to pts enrolled prior to December 31, 2020, and included 108 pts with a median follow-up of 8 months (range 1-20). As of data cut, 93 pts completed cycle 1 of therapy, 66 pts completed cycle 3 and 39 pts completed cycle 6. 29 pts (27%) are still active on treatment. Best composite complete remission [CCR = complete remission (CR) plus CR with incomplete count recovery (CRi)] was achieved in 62 (57%) pts. CCR rates were assessed in different pre-defined subgroups. Best CCR in pts selected for therapy based on disease-related and patient-related factors were 70% and 54% respectively. Best CCR in pts with AML arising from MPN and pts with other AML were 45% and 58% respectively. Estimated median overall survival (OS) of all pts was 9.6 months (range 7.4-10.6) (Figure 1). Achieving CCR was associated with a superior probability for survival. Estimated median OS was 13.6 months (range 10.6 - not reached) in pts achieving CCR and 4.2 months (range 1.2-10.3) in non-CCR (p&lt;.0001). Of responding pts (CR/CRi, partial remission (PR), morphologic leukemia free state (MLFS), 27 (37%) progressed. Estimated median time to progression was 9.2 months (6.7-NR). Allogeneic transplantation following venetoclax based treatment was offered to 16 (26%) pts with a median age of 71 years (range 43-77). Last documented response prior to transplant was CR in 5 (32%) pts, CRi 9 (56%), MLFS 1 (6%) and PR in 1 (6%) patient. Among grade ≥3 AEs were febrile neutropenia in 28% and infections in 21% of pts. Clinical and laboratory tumor lysis syndrome (TLS) was documented in 2 and 4 pts, respectively. Antifungal prophylaxis was administered in 20% of pts and granulocyte colony-stimulating factor (GCSF) support was used in 17% of pts in response. Early death rate at 30 and 60 days were 7% and 13%, respectively. Conclusion: This prospective real-world analysis reveals unique patterns of patient selection and venetoclax treatment utilization in a medical system with wide access for this indication. Venetoclax-based therapies are effective and associated with manageable toxicity, including in AML patient populations that were excluded from previous registration trials with comparable CCR and early death rates. Factors associated with patient selection in the 'real-world' setting and immature follow up data most probably led to a shorter estimated median OS in this analysis as compared to controlled trials. The REVIVE study continues to expand and is expected to provide additional insights on treatment patterns, management as well as clinical and patient related outcomes. Figure 1 Figure 1. Disclosures Wolach: Janssen: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Astellas: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Neopharm: Consultancy. Levi: AbbVie: Consultancy, Research Funding. Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures. Tavor: AbbVie: Consultancy. Hellmann: AbbVie: Consultancy. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Zuckerman: Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria; Cellect Biotechnology: Honoraria; BioSight Ltd: Honoraria; AbbVie: Honoraria; Orgenesis Inc.: Honoraria. Stemer: AbbVie: Consultancy. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Ofran: Medison Israel: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Moshe: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures.

scholarly journals Evaluation and Comparison of Characteristics and Outcomes Among Frontline Multiple Myeloma (FLMM) Patients with and without Stem Cell Transplant Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4738-4738 ◽  
Author(s):  
Ajai Chari ◽  
Maneesha Mehra ◽  
Mary Slavcev ◽  
Annette Lam ◽  
Ravi Potluri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Patient Characteristics ◽  
The United States ◽  
Cell Transplant ◽  
Real World Data ◽  
Advisory Committees ◽  
World Data

Abstract Background: High-dose therapy with autologous stem cell transplantation (SCT) is a standard treatment option in FLMM patients who are ≤65 years of age. Few studies have examined the real-world patient characteristics and outcomes associated with those who receive an SCT compared with non-SCT patients. Aims: To use real-world data to characterize patients with FLMM who received SCT compared with those who did not receive SCT, and determine their overall survival (OS). Methods: Data were extracted from 3 real-world data sources from the United States: Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked (January 2007 to December 2014), OPTUM™ Commercial Claims (January 2000 to March 2017), and OPTUM™ Electronic Medical Records (EMR; January 2007 to March 2016) databases. Patients with 1) an index MM diagnosis on or after 1 January 2007 who 2) had known gender and medical prescription coverage at the time of diagnosis, 3) had a 1-year look-back period prior to index diagnosis, 4) had no prior cancers in the 1-year period prior to index diagnosis, and 5) had at least 1 line of treatment were included. SCT patients were defined as those who received an SCT at any time during their follow-up. Patient characteristics such as age (at index diagnosis), gender, and comorbidities (180 days before start of first line of therapy [LOT1]) were descriptively compared. OS was evaluated from the start of LOT1 using the Kaplan-Meier method and multivariable Cox regression analyses. Results: A total of 9,323 patients were analyzed, comprising 1,599 SCT (17.2%) and 7,724 (82.8%) non-SCT patients. Patient characteristics and OS are summarized in the Table. Descriptive differences in patient characteristics were observed between SCT and non-SCT patients, including median age at start of frontline treatment, gender, and incidences of baseline comorbidities. In terms of survival outcomes, median OS was not reached (NR; 95% confidence interval [CI], 91.8-not estimable [NE]) for SCT patients compared with 45.1 (95% CI, 43.1-46.8) months for non-SCT patients. Age at index diagnosis, gender, time to and year of treatment initiation, and presence of baseline comorbidities were significantly associated with OS. Accounting for differences in these patient characteristics, the adjusted hazard ratio (HR) for OS in non-SCT versus SCT patients was 2.29 (95% CI, 2.01-2.61; P <0.0001). Among the different age subgroups (<65, 65-74, and ≥75 years of age), the OS benefit for SCT versus non-SCT was maintained across these subgroups (Figure). Conclusions: In a real-world setting, FLMM patients who received SCT were younger and had lower rates of several comorbidities at baseline compared with non-SCT patients. A significant OS benefit was observed among patients who had received SCT, underlying the need for more effective treatment options in patients who do not receive SCT. Disclosures Chari: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; The Binding Site: Consultancy. Mehra:Janssen Global Services, LLC: Employment. Slavcev:Janssen Global Services, LLC: Employment. Lam:Janssen Global Services, LLC: Employment. Potluri:SmartAnalyst Inc.: Employment. Kaufman:Abbvie: Consultancy; Roche: Consultancy; BMS: Consultancy; Janssen: Consultancy; Karyopharm: Other: data monitoring committee.

Sign in / Sign up

Export Citation Format

Share Document