scholarly journals Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real‐world evidence from the medicare population

2021 ◽  
Vol 10 (8) ◽  
pp. 2690-2702
Author(s):  
Ravi K. Goyal ◽  
Saurabh P. Nagar ◽  
Shaum M. Kabadi ◽  
Hannah Le ◽  
Keith L. Davis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Real World ◽  
Economic Burden ◽  
Systemic Therapy ◽  
Lymphocytic Leukemia ◽  
Medicare Population ◽  
Real World Evidence

scholarly journals Overall Survival, Adverse Events, and Economic Burden in Medicare Patients with Chronic Lymphocytic Leukemia Receiving Cancer-Directed Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 796-796
Author(s):  
Ravi K Goyal ◽  
Saurabh P Nagar ◽  
Shaum M Kabadi ◽  
Keith L Davis ◽  
Hannah Le ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Economic Burden ◽  
Systemic Therapy ◽  
Index Date ◽  
Lymphocytic Leukemia ◽  
Routine Practice ◽  
Medicare Patients

Background: Data on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) are mostly available from controlled trials, with limited data from routine clinical practice. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in patients treated for CLL. Methods: Patients with CLL receiving ≥ 1 systemic therapy from 2013-2015 were selected from the Medicare claims database and followed through 2016. The date of the start of first observed therapy served as the index date. Patients were required to have at least 12 months of continuous Medicare enrollment with no evidence of systemic therapy for CLL and/or SCT before the index date. An observed therapy regimen was defined as the combination of all agents received within 35 days after (and including) the first claim for a systemic therapy drug. Therapy was considered ended upon switch to a different regimen or a gap ≥ 90 days after the last treatment. OS was assessed from the index date until the last follow-up or death using the Kaplan-Meier method. Incidence of hematologic and nonhematologic AEs during treatments were assessed for the most commonly observed regimens. The incidence of AEs was based on the presence of at least one claim containing an AE-specific diagnosis code during the treatment, regardless of any history of the AE before treatment initiation. All-cause direct medical costs were assessed from the Medicare's perspective. Results: We analyzed 7965 patients (median age=76 years) who met the inclusion criteria. In the overall study follow-up (across all observed therapy lines), ibrutinib monotherapy (Ibr; n=2708) was the most frequent regimen, followed by chlorambucil monotherapy (Clb; n=1620) and bendamustine/rituximab (BR; n=1485). Median length of follow-up from the index date was 19 months for Ibr, 21 months for Clb, and 24 months for BR. Median OS was reached only for Clb (40.8 months [95% CI = 38.6-not reached]). 24-month OS rates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%), respectively. The incidence of the most frequent AEs (occurrence in >10% of patients) are presented in Table1 1; estimates in bold indicate that the incidence of the AE was higher by ≥ 5 percentage points than in the noted trials (Woyach, 2018, N Engl J Med; Burger, 2015, N Engl J Med). The mean per patient per month costs, among all patients, were $1,915 (SD = $2,453) during the baseline period and $8,974 (SD = $11,562) during the period after initiation of the first observed CLL-directed systemic therapy. Mean monthly all-cause costs increased by the number of AEs (from $5,144 [SD = $5,409] among those with 1-2 AEs to $10,077 [SD = $12,542] among those with ≥6 AEs). Conclusion: To our knowledge, this is the largest contemporary observational study reporting outcomes among CLL patients initiating treatments in a real-world setting. Over two-thirds of patients survived ≥2 years after start of the first observed therapy during the study period. Incidence for several hematologic and nonhematologic AEs during the common CLL therapies observed in this study appear to be higher than those reported in the noted clinical trials, highlighting potentially greater susceptibility to these AEs and an unmet medical need in Medicare patients with CLL treated in routine practice. This study also highlights a substantial economic burden that exists in the period after initiation of treatment for CLL. Disclosures Goyal: RTI Health Solutions: Employment. Nagar:RTI Health Solutions: Employment. Kabadi:AstraZeneca: Employment, Equity Ownership. Davis:RTI Health Solutions: Employment. Le:AstraZeneca: Employment, Other: Stocks. Kaye:RTI Health Solutions: Employment.

scholarly journals How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia

Blood ◽  
2019 ◽  
Vol 133 (12) ◽  
pp. 1298-1307 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C. Byrd
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Real World ◽  
Lymphocytic Leukemia ◽  
Targeted Therapeutics ◽  
Therapeutic Approaches ◽  
Therapeutic Alternatives

Abstract Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib’s common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. In particular, atrial fibrillation, bleeding, infections, and arthralgias have been reported. The management of ibrutinib’s adverse events often cannot be generalized but must be individualized to the patient and their long-term risk of additional complications. When ibrutinib was initially developed, there were limited therapeutic alternatives for CLL, which often resulted in treating through the adverse events. At the present time, there are several effective alternative agents available, so transition to an alternative CLL directed therapy may be considered. Given the continued expansion of ibrutinib across many therapeutic areas, investigation of the pathogenesis of adverse events with this agent and also clinical trials examining therapeutic approaches for complications arising during therapy are needed. Herein, we provide strategies we use in real-world CLL clinical practice to address common adverse events associated with ibrutinib.

scholarly journals Retrospective Non-Interventional Assessment of the Use of Idelalisib in Relapsed/Refractory Chronic Lymphocytic Leukemia Patients in Spain

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5473-5473 ◽  
Author(s):  
Christelle M Ferra ◽  
Manuel Perez Encinas ◽  
Javier Lopez Jimenez ◽  
Macarena Ortiz ◽  
Santiago Osorio-Prendes ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Real World ◽  
Research Funding ◽  
Fungal Infections ◽  
Lymphocytic Leukemia ◽  
Cumulative Probability ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Grade 3

Background Idelalisib is a PI3-kinase inhibitor specific for the delta isoform, approved (in combination with rituximab or ofatumumab) for the treatment of adult patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL). Although the efficacy of idelalisib was reported in clinical trials, it is unclear how this translates into Real World. Methods A non-interventional retrospective study was conducted in Spain to describe the clinical characteristics and outcomes of patients diagnosed with R/R CLL that started treatment with idelalisib between 1 February 2015 and 31 December 2017. The Time from start of idelalisib treatment to either the start of a new anti CLL therapy or death (Time to Next Treatment or Death - TNTD) was defined as primary endpoint. Secondary endpoints included overall survival (OS), time to discontinuation (TTD) and safety, especially Adverse Events of Special Interest (AESI): ≥ grade 3 transaminase elevations, diarrhea /colitis, pneumonitis, neutropenia,Cytomegalovirus, bacterial, fungal and respiratory virus infections (RVI),Pneumocystis jirovecii pneumonia (PjP). Results Investigators from 21 centers included 77 patients in the study. The median age was 72.1 years (48-86) and 67.5% (n=52) were male. The main baseline characteristics were: Binet stage B-C in 32.5% (n=25), 17p deletion or TP53 mutation in 35.1% (n=27) and the median number previous lines of therapy was 4 (1-16). With a median follow up time of 14.4 months (1.2-44.4), 27 patients (35.1%) had started a new treatment and 19 (24.7%) had died. The median TNTD was 17.1 months (95% CI 14.0-22.3) in the overall population and 13.8 months (95% CI 7.9-15.2) in patients that discontinued idelalisib. The median OS has not been reached, with a cumulative probability of surviving at 1 and 2 years of 0.84 (95% CI 0.73-0.91) and 0.67 (95% CI 0.52-0.78). During follow-up 54 patients (70.1%) discontinued idelalisib: 39 (72.3%) due to toxicity and 10 (18.5%) due to disease progression. The median TTD was 13.0 months (95% CI 7.7-15.8); 5.3 months (95%CI 3.8-8.0) in patients who discontinued treatment due to serious adverse events (SAE) or AESI and 10.5 months (95% CI 0.5-16.0) in those who did so due to progressive disease. A total of 355 AEs were reported, of which 29.0% (n=103) were SAE. 181 AESIs were recorded: the most frequent were neutropenia (n=67; 22 grade >3), diarrhea/colitis (n=37; 14 grade >3) and bacterial infections (n=24; 14 grade >3). Other AESI were CMV infections (n=11), grade ≥ 3 pneumonitis (n=7), RVI (n=6), fungal infections (n=5), grade ≥ 3 transaminase elevations (n=3) and PjP (n=1). The median time from Idelalisib start to first AESI was 9.5 months (95%CI 5.5-15.3). During follow-up, 19 deaths were registered, 10 of which were caused by idelalisib-related SAEs (4 respiratory infections, 2 pneumonitis, 1 diarrhea/colitis). The time from SAE related to idelalisib that led to death, to death was 0.8 months (95% CI 0.7-1.7). Conclusions This real world study shows results of effectiveness of idelalisib consistent with the efficacy findings of the 312-0116 clinical trial. Toxicity was the most common reason for idelalisib discontinuation. Findings of adverse events were consistent with the known safety profile of idelalisib and no new drug-related adverse events were identified. This is a Gilead Sciences sponsored study. Disclosures Perez Encinas: GILEAD SCIENCES: Research Funding; CELGENE: Consultancy; JANSSEN: Consultancy. Lopez Jimenez:GILEAD SCIENCES: Honoraria, Other: Education funding. Ortiz:GILEAD SCIENCES: Research Funding. Cordoba:Pfizer: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; FUNDACION JIMENEZ DIAZ UNIVERSITY HOSPITAL: Employment; Roche: Honoraria, Speakers Bureau; Kyowa-Kirin: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Ramirez Payer:GILEAD SCIENCES: Research Funding. González-Barca:Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celtrion: Consultancy; AbbVie: Consultancy, Honoraria; Kiowa: Consultancy; Takeda: Honoraria; Celgene: Consultancy. Martín Sánchez:GILEAD SCIENCES: Research Funding. Sanchez:Gilead Sciences: Research Funding. Baltasar Tello:JANSSEN: Consultancy, Honoraria; ABBVIE: Honoraria; ROCHE: Honoraria; GILEAD: Honoraria. Amutio:NOVARTIS: Consultancy; JANSSEN: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria; ROCHE: Honoraria; GILEAD SCIENCES: Consultancy, Honoraria; TAKEDA: Consultancy; GSK: Honoraria; BMS: Honoraria; JAZZ PHARMACEUTICALS: Honoraria; MUNDIPHARMA: Consultancy. Vidal Maceñido:GILEAD SCIENCES: Research Funding. Fernandez:GILEAD SCIENCES: Research Funding. Loscertales:Gilead: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Janssen: Honoraria; Roche: Honoraria. Rodríguez:GILEAD SCIENCES: Research Funding. Alaez:ROCHE: Consultancy. Ramroth:Gilead Sciences: Employment. Palla:Gilead Sciences: Employment.

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