Single-Agent Ibrutinib Vs Standard of Care for Patients with Relapsed/Refractory (R/R) and Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): An Adjusted Comparison of RESONATETM and RESONATE-2TM with the French Lyon-Sud Database

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2039-2039
Author(s):  
Gilles A. Salles ◽  
Lucile Baseggio ◽  
Emmanuel Bachy ◽  
Clementine Sarkozy ◽  
Herve Ghesquieres ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Disease Stage ◽  
Treatment Regimens ◽  
Real World Setting ◽  
Level Data ◽  
Advanced Disease Stage ◽  
Independent Risk Factors ◽  
Male Sex

Abstract INTRODUCTION: The benefits of ibrutinib (ibr) have been demonstrated by the phase 3 RESONATE and RESONATE-2 trials for patients (pts) with R/R and TN (≥ 65 years) CLL, respectively. In these studies, ibr showed significantly improved progression-free survival (PFS) and overall survival (OS) vs approved comparators (ofatumumab [ofa] in RESONATE and chlorambucil [clb] in RESONATE-2). However, a number of other treatment regimens are widely used in clinical practice for CLL based on individual patient and disease characteristics; it is currently unknown if ibr results in better survival outcomes when compared directly with each of these other treatments. AIM: In the absence of a head-to-head comparison, we investigated the relative efficacy of ibr vs physician's choice (PC) in pts with R/R or TN CLL by comparing pt-level data from RESONATE and RESONATE-2 with data from pts in a real-world setting (the Lyon-Sud database). This database holds electronic medical records for 390 pts with CLL from the academic Lyon-Sud Hospital in France; nearly all patients were diagnosed between 1990 and 2014. This is the first analysis of ibr vs PC in a real-world setting for pts with TN CLL. METHODS: Pt-level data from RESONATE (ibr, n = 195; ofa, n = 196) were compared with data on pts with CLL from Lyon-Sud who received 2nd(n = 107) or later-line treatment (3rd [n = 62], 4th [n = 43], and subsequent [n = 51] lines). Similarly, RESONATE-2 (ibr, n = 136; clb, n = 133) pt-level data were compared with those of pts aged ≥ 65 years who received 1st-line treatment (n = 131). In order to account for non-comparability due to lack of randomization, a multivariate Cox proportional hazards model was used to compare PFS and OS between treatments, including line of therapy, age, sex, disease stage (based on Binet/Rai), and deletion 17p or 11q mutations as covariates. For the definition of PFS, missing data for date of disease progression for pts in Lyon-Sud who initiated subsequent therapy were replaced by the conservative proxy of date of initiation of next treatment. Predicted PFS and OS curves for the Lyon-Sud cohort were derived from the multivariate model. RESULTS: For R/R pts in Lyon-Sud, across all treatment lines the most frequent regimens used were rituximab (R) + chemotherapy (n = 46), bendamustine + R (BR; n = 28), fludarabine + cyclophosphamide + R (FCR) (n = 27), clb + R (n = 19), R monotherapy (n = 21), and R-CHOP-based (n = 19); the remaining percentages comprised various other therapies, each used in < 5% of pts. Median age at treatment initiation for Lyon-Sud and RESONATE was 69 and 67 years, respectively; median number of prior therapies was 2 and 3, and median follow-up was 30.0 and 21.9 months. More lines of prior therapy, older age, male sex, advanced disease stage (Binet C/Rai III/IV), and presence of deletion 17p/11q were independent risk factors for worse PFS and OS outcome. After adjustment for differences in baseline characteristics, PFS and OS hazard ratios (HRs) for ibr vs PC were 0.18 (95% confidence interval [CI], 0.13-0.26) and 0.28 (0.17-0.46), respectively. Adjusted HRs for ibr vs the most frequent treatments ranged from 0.09 (R monotherapy) to 0.38 (FCR) for PFS and 0.21 (R monotherapy) to 0.33 (FCR) for OS; all were statistically significant. For TN pts in Lyon-Sud, the most frequent treatment regimens used were FCR (n = 40), clb + R (n = 21), clb monotherapy (n = 17), R-(mini)CHOP (n = 11), and BR (n = 11). Median age at treatment initiation was 73 years for both Lyon-Sud and RESONATE-2; median follow-up was 36.9 and 28.1 months, respectively. Older age, male sex, and advanced disease stage were independent risk factors for worse PFS and OS outcome. After adjustment for baseline differences, the PFS and OS HRs for ibr vs PC were 0.25 (0.14-0.47) and 0.41 (0.17-0.99). Predicted PFS and OS curves for both R/R and TN patients are presented in Figure 1. CONCLUSIONS: Investigation of survival outcomes suggests that ibr administered to pts in RESONATE and RESONATE-2 was more effective than PC used in a real-world cohort of French pts with R/R or TN CLL, suggesting a 4.8-fold improvement in PFS and a 3.4-fold improvement in OS in R/R pts and 4-fold and 2.4-fold improvements in TN pts, respectively. These results further support the growing evidence that ibr significantly improves both PFS and OS vs commonly used regimens in the R/R and TN settings, and could have important implications for improving treatment of CLL in clinical practice. Disclosures Salles: Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding. Sarkozy:Sandoz: Research Funding; Janssen Research & Development: Honoraria; Gilead: Honoraria; Takeda: Research Funding. Ghesquieres:Mundipharma: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche France: Research Funding. Diels:Johnson & Johnson: Employment, Equity Ownership. Besson:Janssen: Employment. MacDougall:Janssen Research & Development: Research Funding; IMS Health: Employment. Hermans:Janssen Research & Development: Research Funding; IMS Health: Employment. Healy:Janssen Research & Development: Employment. Garside:Janssen Research & Development: Employment. Iraqi:Janssen Research & Development: Employment.

Shifting Treatment Patterns and Clinical Outcomes in Veterans Diagnosed with Waldenstrom Macroglobulinemia from 2006 to 2018

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Hsu-Chih Chien ◽  
Deborah Kay Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Christina Yong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Real World ◽  
Research Funding ◽  
Practice Patterns ◽  
Treatment Patterns ◽  
Clinical Settings ◽  
Treatment Groups ◽  
Treatment Regimens

Background Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with an estimated 1,500 new cases diagnosed each year in the United States (US). Over the last decade, several treatments have been introduced into the WM therapeutics landscape including, bendamustine, bortezomib, and most recently oral Bruton's kinase inhibitor (ibrutinib). There is limited information in the adoption of these WM treatments in real-world clinical settings in the US. We describe the practice patterns and clinical outcomes of first-line (1L) treatment of WM in a nationwide cohort of Veterans. Methods Using Veteran Affairs electronic health records (EHR) data, we identified Veterans who were diagnosed and received 1L treatment for WM between January 2006 and December 2018 in the Veterans Health Administration (VHA). Human annotation of EHR clinical records confirmed the diagnosis and 1L treatment regimens. Patients with another cancer diagnosis or patients with documentation that 1L treatment was received outside the VHA were excluded. Eligible patients were followed until loss to follow-up, death, or the end of the study period (June 30, 2019). Patient demographics, disease characteristics, and treatment patterns were identified. Local polynomial regression model curves were generated to demonstrate treatment changes over time. Unadjusted progression-free survival (PFS) and the unadjusted overall survival (OS) are also provided. Results We identified 505 patients diagnosed with WM in VHA between January 2006 thru December 2018. Of these, 318 patients received 1L treatment, with a median time from diagnosis to 1L treatment of 1.2 months (95% confidence interval [CI]: 0.5-5 months). The median age of WM patients was 69.9 years (standard deviation [SD]: 9.4 years), with approximately 73% of WM patients ≥65 years old. Prior to 1L treatment, the median hemoglobin and platelets observed were similar across all treatment groups, regardless of first 1L treatment. However, the median immunoglobulin M (IgM) was substantially lower in patient's treated with ibrutinib (2,570 mg/dL [range: 422-9,001 mg/dL]) and single-agent rituximab (R), 2,855 mg/dL (range: 84-7,880 mg/dL) when compared to those treated with chlorambucil +/- rituximab (4,416 mg/dL [range: (9-8,130 mg/dL]) and bortezomib/dexamethasone +/- rituximab (BDR), 4,086 mg/dL (range: 16-9,944 mg/dL). MYD88 testing occurred in 40 (13%) of patients, with testing most frequently occurring in patients treated with bendamustine +/- rituximab (BR), ibrutinib, and BDR- likely reflecting increased adoption in later periods. Hepatitis C testing occurred in 61 (19%) of patients, with testing most frequently occurring in patients treated with dexamethasone, rituximab, and cyclophosphamide (DRC), BDR, and BR. Over the study observation period, 1L practice patterns shift significantly with increased adoption of BR, BDR and ibrutinib and de-adoption of chemotherapy (Figure 1). The median follow-up time for all patients was 44 months (range: 1-147 months), although a shorter median follow-up time was observed in patients treated with therapeutics in recent years, such as ibrutinib (18 months [range: 2-53 months]) and BR (23 months [range: 4-86 months]). The median unadjusted PFS for all WM patients was 44 months (95% CI: 37-58 months) and the median unadjusted overall survival (OS) was 94 months (95% CI: 82-117 months). Conclusions The introduction of numerous therapeutic options throughout the past decade has profoundly altered the treatment landscape for WM, suggesting a shift in 1L practices from chlorambucil to BDR, BR, and most recently ibrutinib which has been increasingly adopted, since its approval in 2015, especially in older patients, suggesting that it may provide an effective therapeutic option for patients who may not be able to tolerate more aggressive treatment regimens. Limitations of this study include the differences observed in follow-up time as well as the limited number of patients in some 1L treatment groups. Further research is required to establish the long-term benefits and potential treatment-related toxicities of WM treatments in real-world clinical settings. Disclosures Sauer: Roche: Research Funding; Genentech, Inc.: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding. Halwani:AbbVie: Research Funding; Takeda: Research Funding; Roche: Research Funding; Genentech, Inc.: Research Funding; Miragen: Research Funding; Immunedesign: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Bristol Myers Squibb: Research Funding.

scholarly journals Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4075-4075
Author(s):  
Michel Delforge ◽  
Marie-Christiane Vekemans ◽  
Sébastien Anguille ◽  
Julien Depaus ◽  
Nathalie Meuleman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Retrospective Chart Review ◽  
Standard Of Care ◽  
Real World Data ◽  
Advisory Committees ◽  
Treatment Regimens

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p&lt;0.001), being male (p=0.001), older age (p&lt;0.001), shorter duration of prior lines (p&lt;0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p&lt;0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of &lt;10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

scholarly journals Real-World Treatment Patterns Among a Contemporary Cohort of Commercially Insured Mantle Cell Lymphoma Patients in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4845-4845
Author(s):  
Lindsey E. Roeker ◽  
Shaum Kabadi ◽  
Chakkarin Burudpakdee ◽  
Aimee Near ◽  
Keiko Wada ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Research Funding ◽  
Index Date ◽  
Treatment Patterns ◽  
Treatment Regimens ◽  
Oral Medications ◽  
Mantle Cell ◽  
Insured Patients

Abstract Introduction Mantle cell lymphoma (MCL) is a rare, aggressive non-Hodgkin lymphoma associated with a poor prognosis. The approval of ibrutinib in November 2013 has changed the treatment paradigm for patients with relapsed or refractory MCL. There remains a lack of information on the current treatment patterns used in clinical practice in a contemporary cohort of commercially insured patients. We aimed to identify the treatment patterns for MCL overall and by line of therapy (LOT) and to describe patient demographics and clinical characteristics in a large cohort of commercially insured MCL patients. Methods A retrospective cohort study was conducted with the IQVIA Real-World Data Adjudicated Claims-US database. Adult patients (≥18 years old) with ≥1 claim for a NCCN-recommended MCL treatment between November 1, 2013 and December 31, 2017 were identified. Index date was the first treatment claim. Patients were also required to have ≥1 diagnosis of MCL during the study period (November 1, 2012 to January 31, 2018), ≥12 months of continuous enrollment prior to index date (pre-index period) and ≥30 days after index date (follow-up period). Patients were excluded if they were ≥65 years at index and not enrolled in Medicare Risk or Medicare Cost, enrolled in a clinical trial during the study period, had evidence of MCL treatment in the pre-index period (except for patients indexed on ibrutinib as it is indicated for MCL patients with ≥1 prior treatment), or had evidence of stem cell transplant (SCT) before index date. The most commonly observed MCL treatment regimens were identified, and demographic and clinical characteristics of patients and treatment durations by regimen were described. Treatment regimen was defined as the combination of all agents observed in the 35-day period after the first MCL treatment claim; treatment duration was defined as the start of treatment until a gap of ≥90 days between end date and next date of treatment or treatment modification. Treatment end date occurred 90 days after the end of the supply for oral medications or 30 days after the last administration for non-oral medications. Results There were 1,785 patients treated with the most commonly observed MCL treatment regimens. The most common regimens, irrespective of LOT, were rituximab monotherapy (including maintenance therapy; n=773, 43.3%), R-CHOP (n=723, 40.5%), B-R (n=436, 24.4%), and ibrutinib monotherapy (n=199, 11.1%). Overall, patients had a median (IQR) age of 57 (52-62) years, and 59.4% were male. Most patients were commercially or self- insured (57.5% and 33.6%, respectively). Patients had a median Charlson Comorbidity Index (CCI) of 0 (IQR 0-1; mean [SD] 0.9 [1.4]), with the most common CCI components being diabetes (15.7%), chronic pulmonary disease (12.8%), and congestive heart failure (9.5%). During the follow-up period (median [IQR] 22.5 [10.5-35.3] months), in addition to the MCL regimen(s), patients received radiation therapy (17.4%), SCT (10.0%), and/or immunotherapy (0.2%). The use of targeted therapies (i.e. lenalidomide, bortezomib) other than ibrutinib was infrequent. When considering treatment lines, R-CHOP was the most commonly observed first regimen, followed by rituximab, B-R, and ibrutinib; for the second and third observed regimens, rituximab was the most common, followed by ibrutinib (Figure 1). The median (IQR) duration for the first observed regimen was 8.1 (3.9-18.0) months for ibrutinib, 5.0 (3.3-5.6) months for B-R, 4.0 (2.5-4.4) months for R-CHOP, and 1.9 (1.7-4.4) months for rituximab; ibrutinib also had the longest duration in the second and third line (median [IQR] 5.5 [2.4-13.5] months and 8.3 [3.9-12.4] months, respectively). Conclusion This is the largest study of MCL patients describing treatment patterns in current clinical practice among commercially insured patients. MCL patients were most commonly treated with chemoimmunotherapy for all treatment lines while ibrutinib was the second most common LOT2 and LOT3 regimen. As the treatment landscape and clinical practice continues to change with the use of novel agents, future studies are warranted to further study toxicities and outcomes in the real-world setting. Disclosures Kabadi: AstraZeneca: Employment. Burudpakdee:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Near:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Wada:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Mato:TG Therapeutics: Research Funding; Sunesis: Honoraria, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Prime Oncology: Speakers Bureau; Abbvie: Consultancy.

scholarly journals Efficacy of Ibrutinib-Rituximab versus Real-World (RW) Treatments for Patients with Waldenström's Macroglobulinemia (WM): Adjusted Comparison of iNNOVATE and the Lyon-Sud RW Database

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1604-1604
Author(s):  
Lionel Karlin ◽  
Hervé Besson ◽  
Christoph Tapprich ◽  
Jamie Garside ◽  
Gilles Salles
Keyword(s):  
Clinical Practice ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Advisory Committees ◽  
Patient Level Data ◽  
Treatment Regimens ◽  
Patient Level ◽  
Kaplan Meier ◽  
Level Data

Abstract Introduction Ibrutinib, a first-in-class, oral, covalent inhibitor of Bruton's tyrosine kinase, is approved in several countries as monotherapy for adults with WM, based on the high response rate (90.5%) observed in a phase 2, single-arm trial of symptomatic patients who had received ≥ 1 prior therapy (NCT01614821; Treon SP, et al. N Engl J Med. 2015;372:1430-1440). In the phase 3 iNNOVATE trial (NCT02165397; Dimopoulos MA, et al. N Engl J Med. 2018;378:2399-2410), adding rituximab to ibrutinib (IR) led to a statistically significant improvement in progression-free survival (PFS) compared with placebo-rituximab, in both treatment-naïve (TN) patients and those with disease recurrence. This analysis examined the relative treatment effect of IR versus other RW treatment regimens used in daily clinical practice in TN and relapsed/refractory (R/R) WM. An adjusted comparison was conducted using patient-level data from the iNNOVATE trial and the Lyon-Sud RW database in France. Methods The Lyon-Sud database holds medical records for patients with WM diagnosed between 1980 and 2017 from the Centre Hospitalier Lyon-Sud. PFS and overall survival (OS) outcomes were compared between the IR arm of iNNOVATE and RW physicians' choice (PC) treatment in Lyon-Sud (excluding RW ibrutinib). Kaplan-Meier survival curves by patient cohort were generated for both end points. A multivariate Cox proportional hazards model was fitted on the pooled patient-level data from both sources to estimate adjusted hazard ratios (HRs) for effect of IR on PFS and OS versus RW treatment, with age, sex, and treatment line as covariates. The unit of observation for the RW databases was the treatment line (rather than the patient) number, whereby RW patients receiving multiple treatment lines contributed to multiple observations, and baseline was defined as the line-specific treatment start date. Results Overall, 242 treatment lines from patients with WM were identified from the Lyon-Sud database; 224 were analyzed. Baseline characteristics were comparable between the IR arm of iNNOVATE (n = 75) and the RW cohort: 62.7% versus 66.5% ≥ 65 years of age; line of therapy, 45.3% versus 48.7% TN [1L], 25.3% versus 25.0% second-line [2L], and 29.3% versus 26.3% third-line or later [3L+]. Median follow-up was 26.7 months for iNNOVATE and 68.5 months for the RW cohort. Non-ibrutinib PC regimens in the RW cohort included rituximab (n = 51 treatment lines), chemotherapy (n = 66; including chlorambucil, n = 31), rituximab-cyclophosphamide-dexamethasone (n = 35), rituximab-CHOP/CHOP-like (n = 21), rituximab-chlorambucil (n = 15), fludarabine-cyclophosphamide-rituximab (n = 14), bendamustine-rituximab (n = 10), other rituximab-containing chemoimmunotherapy (n = 10), and rituximab-targeted agent (n = 2). Two ibrutinib lines were excluded from the RW cohort analysis. Figures A and B show the observed 1L+ Kaplan-Meier curves for IR versus RW PC therapy for all analyzed patients with WM (unadjusted HRs: 0.32 [95% confidence interval (CI), 0.19-0.55] for PFS and 0.38 [95% CI, 0.13-1.09] for OS). After adjusting for differences in patient characteristics, HRs (1L+ therapy) became 0.28 (95% CI, 0.16-0.48; p < 0.001) for PFS and 0.29 (95% CI, 0.09-0.93; p = 0.037) for OS. Restricting the analysis to 1L treatment only (Lyon-Sud n = 109; iNNOVATE n = 34), the adjusted HRs were 0.25 (95% CI, 0.09-0.70; p < 0.009) for PFS and 0.20 (95% CI, 0.02-2.00; p = 0.170) for OS; respective unadjusted HRs were 0.31 (95% CI, 0.12-0.78) and 0.30 (95% CI, 0.04-2.34). In the 2L+ setting (Lyon-Sud n = 115; iNNOVATE n = 41), the adjusted HRs were 0.28 (95% CI, 0.15-0.56; p < 0.001) for PFS and 0.34 (95% CI, 0.08-1.35; p = 0.126) for OS; respective unadjusted HRs were 0.31 (95% CI, 0.16-0.61) and 0.39 (95% CI, 0.12-1.31). Concl usions In the absence of randomized controlled trial data for ibrutinib versus other treatment regimens for WM, these adjusted comparisons of clinical trial and RW patient-level data suggest that IR significantly improves both PFS and OS versus RW PC regimens as 1L+ therapy. These results help inform physicians on the standard of care for WM in clinical practice. Funding Source: This project was sponsored by Janssen Pharmaceutica NV, and Pharmacyclics LLC, an AbbVie Company. The real-world databases are independently owned. Writing assistance was provided by Emma Fulkes of PAREXEL and funded by Janssen Pharmaceutica NV. Disclosures Karlin: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Besson:Janssen Pharmaceutica NV: Employment. Tapprich:Janssen Pharmaceutica NV: Employment. Garside:Janssen Pharmaceutica NV: Employment. Salles:Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; AbbVie: Honoraria; Acerta: Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria; Merck: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Servier: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Epizyme: Honoraria; Morphosys: Honoraria.

scholarly journals Efficacy of Front-Line Ibrutinib Versus Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients with CLL. a Multicenter "Real-World" Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2641-2641
Author(s):  
Yair Herishanu ◽  
Shai Levi ◽  
Neta Goldschmidt ◽  
Fortunato Morabito ◽  
Osnat Bairey ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Cox Regression ◽  
Phase Iii ◽  
Front Line ◽  
Advisory Committees ◽  
Real World Setting ◽  
Binet Stage

Abstract Introduction: In previously untreated patients with chronic lymphocytic leukemia (CLL), treatment with ibrutinib plus rituximab improved progression-free survival (PFS) and overall survival (OS) compared to the standard fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapeutic regimen, based on the results of the phase III ECOG-E1912 trial. The improvement in PFS with ibrutinib plus rituximab was observed in patients with unmutated immunoglobulin heavy chain variable region gene (IGHV) but not in those with an IGHV mutated profile. However, the efficacy of ibrutinib compared to FCR has not yet been investigated in the real-world setting. Methods: A multi-center retrospective "real-world" study to compare the efficacy of front-line ibrutinib monotherapy versus standard FCR in patients with CLL. Demographic and clinical data of the FCR cohort were retrieved from the Israeli CLL Study Group database and of the ibrutinib from the Italian multicenter "Campus CLL" network and the CLL database of the department of hematology at the Sourasky Medical Center. Patients with a documented del(17p) or those who are participating in clinical trials were excluded. In order to fit both treatment samples, the maximum follow-up was censored at 48 months. IBM SPSS Statistics was used to analyze PFS and OS by Kaplan Meier Estimator, Log-Rank test and Cox Regression. In order to control for differences in patients' characteristics, the inverse probability of treatment weighting (IPTW) method with stabilized weights and truncation of 5% extreme score was applied by R. Results: A total of 235 patients who had been front-line treated with either FCR (n=136, 57.9%) or ibrutinib (n=99, 42.1%) were included (Table 1). Most patients were males (n=160, 68.1%), had an unmutated IGHV status (n=115, 70.6%) and were Binet stage B/C (n=191, 83.8%). By FISH, the most frequent abnormality was del(11q) (n=45, 23.1%) followed by trisomy12 (n=34, 17.4%) and del(13q) (n=43, 22.1%). Median time to first treatment was 29.4 months (IQR, 11.9-56.2), and it was not significantly different between ibrutinib (median=24.9 months, IQR 10.3-46.6) and FCR (median=34.0 months, IQR 13.8-60.1; p=0.101). Patients treated with FCR were younger than those treated with ibrutinib (median=58.4 years vs. 71.9 years; p&lt;0.001). The median follow-up for the entire cohort was 48.0 months (37.2 months and 48 months for ibrutinib and FCR, respectively). PFS was longer with ibrutinib than with FCR, with a 3-year rate of PFS of 89.7% vs. 65.8%, respectively (HR=3.5, 95% CI [1.8-6.9], p&lt;0.001) (Figure 1). By subgroup analysis, the PFS benefit with ibrutinib over FCR was maintained in the subgroups of patients age &gt;65 years (n=100, 3-year PFS 89.4% vs. 53.1%; HR=3.9, 95% CI [1.6-9.9], p=0.002), Binet stage B/C (3-year PFS: 90.5% vs. 67.8%; HR=3.5, 95% CI [1.7-7.5], p&lt;0.001) and unmutated IGHV (3-year PFS: 83.0% vs. 78.0%; HR=5.8, 95% CI [2.4-14.5], p&lt;0.001). Among mutated IGHV patients the PFS was not significantly different between ibrutinib and FCR (3-year PFS: 83.0% vs. 78.0%; HR=1.2, 95% CI [0.3, 4.5]; P=0.795). In multivariate analysis (Table 2), only FCR was an independent predictor of decreased PFS (HR=5.1, 95% CI [1.8, 14.3], p=0.002). OS was also better with ibrutinib than with FCR, with a 3-year OS of 96.8% vs. 87.5%, respectively (HR=3.52, 95% CI [1.04-11.92], p=0.031) (Figure 2). Using IPTW, both PFS and OS were still superior with ibrutinib compared to FCR (HR=0.2, 95% CI 0.1-0.5, p&lt;0.001 and HR=0.2, 95% CI [0.1-0.7], p=0.008, respectively). Conclusions: In a real-world setting, front-line treatment with ibrutinib improves PFS and OS in patients with CLL. Similar to the results of the phase III ECOG-E1912 trial, the improvement in PFS was preferentially observed in patients with unmutated IGHV. Figure 1 Figure 1. Disclosures Herishanu: AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Medison: Honoraria. Goldschmidt: AbbVie: Consultancy, Research Funding. Fineman: AbbVie: Research Funding. Mauro: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Tskeda: Consultancy, Honoraria. Reda: Abbvie: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Laurenti: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Gilead: Honoraria; Roche: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Shvidel: AbbVie: Honoraria, Research Funding. Coscia: Janssen: Honoraria, Other, Research Funding; Gilead: Honoraria; AbbVie: Honoraria, Other; AstraZeneca: Honoraria. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Varettoni: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; beigene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; roche: Membership on an entity's Board of Directors or advisory committees. Aviv: AbbVie: Honoraria, Research Funding. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Rossi: Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Verastem: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Cellestia: Honoraria, Research Funding. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo: AbbVie: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Gattei: abbVie: Research Funding; Janssen: Research Funding; Menarini: Research Funding.

scholarly journals Treatment Patterns and Outcomes of Patients with Relapsed or Refractory Follicular Lymphoma Treated with Idelalisib in a Community Oncology Setting

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2810-2810
Author(s):  
David Andorsky ◽  
Rebecca J Chan ◽  
Jamyia Clark ◽  
Bianca Ruzicka ◽  
Nicholas James Robert ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
Real World ◽  
Research Funding ◽  
Treatment Patterns ◽  
Employment Equity ◽  
Real World Setting ◽  
Equity Ownership ◽  
Systemic Therapies

Introduction: Idelalisib (IDELA, Zydelig®) is the first-in-class PI3Kδ inhibitor and is approved in the U.S. as an oral monotherapy for relapsed / refractory follicular lymphoma (R/R FL) after at least two prior lines of systemic therapy. IDELA's regulatory approval was based on a phase 2, open-label clinical trial in 125 patients with R/R indolent non-Hodgkin's lymphoma (Gopal et al., NEJM, 2014) and outcomes in the FL subgroup were published by Salles et al. (Haematologica, 2017). The current study evaluates the characteristics and treatment patterns of patients treated with IDELA for R/R FL in a real-world setting. Methods: Adult patients diagnosed with R/R FL (grades 1, 2, and 3a) and treated with IDELA within the US Oncology Network (USON) between 7/1/2014 to 6/30/2018 were analyzed retrospectively. Patient data were obtained from USON's structured electronic health records' system, iKnowMed (iKM)TM. Manual chart review (ChR) was used to determine physician response and to confirm IDELA treatment patterns. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods. Descriptive statistics were generated for outcomes of interest, including duration of therapy (DoT), median follow-up, and adverse event (AE) frequency. Results: A total of 124 patients with FL and prescribed IDELA were identified in iKM TM. After Chr confirming the diagnosis of follicular lymphoma diagnosis and initiation of IDELA, 88 patients were retained for analysis. Median age of patients was 68.9 years, with 52.3% female and the majority white and non-Hispanic (90.9% and 93.2%, respectively, Table 1). The most common regimens immediately prior to IDELA initiation were bendamustine + rituximab (22.7%), rituximab (17%), and rituximab maintenance (11.4%). Eighty-six (97.7%) patients had co-morbidities categorized as vascular (50%), endocrine (33%), respiratory (13.6%), or cardiac (12.5%). Thirteen (14.8%), 21 (23.9%), and 54 (61.4%) patients initiated IDELA in second line (2L), 3L, and >4L, respectively. Baseline lab values at IDELA initiation were similar regardless of line of therapy (LOT). mDOT was 5.5 mos. for the entire population and was similar across all LOTs (4.1 mos., 6.1 mos., and 5.5 mos. in 2L, 3L, and >4L, respectively). AEs were noted in 45.5% with the most common being gastrointestinal (31.8%) and dermatologic (10.2%). Respiratory and infectious AEs were noted in 2.3% and 1.1%, respectively, although Pneumocystis jirovecii pneumonia (PJP) prophylaxis was rarely prescribed (2.3%). Toxicity as a reason for IDELA discontinuation varied in frequency across LOT and was more common in 2L compared to 3L and >4L (91.7% compared to 43.8% and 46.9%, respectively). With a median follow-up of 18.6 months for the population, the mPFS was 11.4 mos. [95%CI: 8.5,17.0] and mOS was 32.5 mos. [95% CI: 25.3,NR]. Stratified by LOT, median follow-up time, mOS, and mPFS were greater in 2L (30.8 mos., NR [95% CI: 27.37,NR], and 29.0 mos. [95% CI: 8.6,NR], respectively) than in 3L or >4L (3L: 17.9 mos., 29.4 mos. [95%CI: 18.6,NR], and 17.5 mos. [95% CI: 6.1,NR]; >4L: 16.5 mos., 25.3 mos. [95%CI: 13.5.,NR], and 8.6 mos. [95% CI: 6.1,12.6], respectively, Figures 1 and 2). Conclusion: Findings from this analysis suggest that R/R FL patients treated with IDELA in a real-world setting experience a similar mDOT and mPFS as those treated in the clinical trial setting (Salles et al., Haematologica, 2017). Patients treated in 2L demonstrated longer PFS and OS compared to later lines, but also experienced increased IDELA discontinuation due to toxicity, perhaps reflecting a lower incidence of progressive disease in earlier treatment lines, or a more immunocompetent population leading to higher rates of autoimmune AEs. Use of PJP prophylaxis in IDELA-treated patients was uncommon, an observation suggesting an opportunity for provider education. Our findings enhance available data on relapsed FL patient outcomes in real-world clinical practice and support the use of IDELA in patients with R/R FL after at least 2 systemic therapies. Disclosures Andorsky: Gilead: Research Funding; Genetech: Research Funding; CTI: Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding. Chan:Gilead Sciences, Inc.: Employment, Equity Ownership. Clark:McKesson: Consultancy, Employment, Equity Ownership. Ruzicka:Gilead Sciences, Inc.: Employment. Robert:McKesson: Employment. Awan:Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Gilead: Consultancy. OffLabel Disclosure: Idelalisib is a PI3 kinase inhibitor indicated for the treatment of patients with relapsed follicular B-cell lymphoma who have received at least two prior systemic therapies. Some patients in this observational study used Idelalisib after one prior systemic treatment.

scholarly journals The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4684-4684
Author(s):  
Stefano Molica ◽  
Potito Rosario Scalzulli ◽  
Lydia Scarfo ◽  
Attilio Guarini ◽  
Roberta Murru ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Research Funding ◽  
Retention Rate ◽  
Preliminary Evaluation ◽  
Long Term Outcome ◽  
Real World Setting ◽  
Number Of Patients ◽  
One Year

Abstract Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%; COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%; grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the first real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures Molica: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Sanna: Janssen: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding; AbbVie: Honoraria, Other; AstraZeneca: Honoraria; Gilead: Honoraria. Reda: Abbvie: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Tafuri: Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2275
Author(s):  
Juan J. Gorgojo-Martínez ◽  
Manuel A. Gargallo-Fernández ◽  
Alba Galdón Sanz-Pastor ◽  
Teresa Antón-Bravo ◽  
Miguel Brito-Sanfiel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Real World ◽  
Primary Outcome ◽  
Baseline Hba1c ◽  
Real World Setting ◽  
Antihyperglycemic Therapy ◽  
The Mean ◽  
Hba1c Levels

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

scholarly journals Sequence of Second Generation Tyrosine Kinase Inhibitors (TKIs) in the Treatment of Patients with Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukaemia - Real World Experience in the UK

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3434-3434
Author(s):  
Jenny Byrne ◽  
Joanne Ewing ◽  
Adam J. Mead ◽  
Heather Oakervee ◽  
Gavin Campbell ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Educational Support ◽  
Third Line ◽  
The Uk ◽  
Observation Period

Background: The prognosis of patients with chronic-phase myeloid leukaemia (CML) has drastically improved with the introduction of tyrosine kinase inhibitors (TKIs). During the period of this study, availability of treatment options in the UK were limited and determined by the date reimbursement was granted and when restrictions on the use of individual licensed TKIs were removed. Currently, imatinib, nilotinib and dasatinib are reimbursed for 1st line treatment (1L) with bosutinib and ponatinib reimbursed for 2nd line or subsequent lines of treatment. Aims: The primary aim was to determine the sequence of 2nd generation (2G) TKIs (nilotinib, dasatinib, bosutinib) in patients with chronic-phase Philadelphia chromosome-positive (Ph+) CML who had received their 3rd and subsequent lines of TKIs in a real world UK setting. Methods: A multi-centre, retrospective, chart review was undertaken in the UK from November 2018 to July 2019. To be included, patients had to be aged ≥18 with chronic phase Ph+ CML who had started a third line of TKI treatment between June 2013 and February 2018. Patients were excluded if they had &gt;3-month gap in treatment before progression or relapse, or were treated with a 2G TKI within an interventional clinical study during third line treatment. At each line, molecular responses, cytogenetic responses, duration of therapy and reasons for stopping were recorded until the date of last hospital follow-up or death. Overall survival was determined from date of initiation of 3rd or 4th line TKI therapy until death by any cause. Results: An interim analysis was undertaken for 65 patients from 11 sites. Median age at diagnosis was 53.0 years. 50.8% were male and 49.2% were female. Of these 65 patients, 48 patients were still being treated at the end of observation (29 patients in 3rd, 18 in 4th and 1 in 5th line). Patient demographics are typical of CML populations. Throughout the study, imatinib was 1L treatment of choice for the majority of patients (57/65; 88%) and this held true (21/22; 95%) even when nilotinib and dasatinib were reimbursed for use 1L. Nilotinib was most commonly prescribed in 2L (42/65; 56%), reflecting the greater availability of this drug during the study period. Dasatinib and bosutinib constituted 22% and 4% respectively of 2L treatments. The most frequent sequencing pathway observed was I1-N2-D3 (Table 1, Fig. 1). 19 other pathways at low frequencies were observed across 39 patients. 97% of patients (63/65) achieved an optimal response at any time as defined by the 2013 ELN guidelines (Table 2) during the observation period. Of the 31 (48%) patients who were resistant to 1L, 24 (37%) achieved a response in 2L and of the 7 (10.7%) patients who were resistant to 1L and 2L, 5 (7.7%) achieved a response in 3L. At the end of the observation period, only 2 (3%) patients never achieved a response. In 3L: 29 (45%) patients are still ongoing, 4 died, 3 were lost to follow up and 3 underwent transplantation. In 4L: 18 (69%) are still ongoing, 3 died, and 3 underwent transplantation. Median overall survival for L3 was 21 months and 12 months in L4. In all lines of treatment, the main cause of switching away from imatinib was lack of efficacy (61%), and for all 2G TKIs the main cause was intolerance (66%). During the period when only imatinib was available in 1L, median duration of 1L treatment was longer at 26 months for patients failing to respond vs 9 months when nilotinib and dasatinib were also available. Conclusions: In this UK real-world study, for patients requiring 3 or more lines of treatment, sequencing of TKIs may have been determined by drug reimbursement. As availability of TKIs increased, time to switch therapy decreased for all patients, suggesting that clinicians were following guidelines and switching treatments more readily. However, initial 1L prescribing behaviour has not changed in this observation period despite better access to 2G TKI, and there appears to be a trend of physicians preferring to repeat 2G TKIs treatment sequences that yield a favourable outcome. Disclosures Byrne: Ariad/Incyte: Honoraria, Speakers Bureau. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Mead:Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; Bristol Myers-Squibb: Consultancy; CTI: Honoraria, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding. Oakervee:Novartis: Honoraria; Pfizer: Honoraria; Bristol Myers-Squibb: Honoraria. Campbell:Novartis: Consultancy, Other: Educational support; Takeda: Consultancy, Other: Educational support; Bristol Myers-Squibb: Other: Educational support; Roche: Other: Educational support; Celgene: Other: Educational support. Amott:Celgene: Other: Meeting attendance sponsorship . Goringe:Novartis: Consultancy, Other: Speaker. Heartin:Celgene: Other: Speaker's fees; Janssen: Other: Speaker's fees; Takeda: Other: Speaker's fees; Alexion: Other: Speaker's fees; Novartis: Other: Speaker's fees. Dimitriadou:Celgene: Other: Meeting attendance sponsorship . Arami:Takeda: Other: Meeting attendance sponsorship ; Gilead: Other: Meeting attendance sponsorship ; Roche: Other: Meeting attendance sponsorship ; Celgene: Other: Meeting attendance sponsorship . Neelakantan:Novartis: Honoraria; Celgene: Honoraria. Frewin:Novartis: Consultancy, Other: Meeting attendance sponsorship ; AbbVie: Other: Meeting attendance sponsorship . Pillai:Celgene: Honoraria. De Lavallade:BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Incyte biosciences: Honoraria, Research Funding, Speakers Bureau. Cross:Novartis: Consultancy, Research Funding; Incyte: Consultancy. Thompson:Incyte: Employment.

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