Effectiveness and Safety Outcomes in Patients with Hemophilia a Receiving Antihemophilic Factor (Recombinant) for at Least 5 Years in a Real-World Setting: 6-Year Interim Analysis of the Ahead International and German Studies

Introduction: Long-term effectiveness and safety data in patients treated in routine clinical practice settings can be captured from real-world studies. The international (INT) and German (GER) Antihemophilic factor (recombinant; rAHF) Hemophilia A (HA) outcome Database (AHEAD) studies assess long-term effectiveness and safety outcomes in patients with moderate HA (factor VIII level 1-5%) or severe HA (factor VIII <1%) receiving rAHF (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in routine clinical practice. Methods: These are non-interventional, prospective, long-term, multicenter studies (INT: NCT02078427; GER: DRKS 00000556). Key outcomes include Gilbert scores (primary endpoint; pain scored 0-3; bleeding scored 0-3, and physical exam scored 0-12), annualized bleeding rates (ABRs) by disease severity, and adverse events (AEs). Findings reported here are from the 6-year interim analysis (data cut-off: July 15, 2019), and focus on patients who have received rAHF prophylaxis or on-demand (OD) treatment for ≥5 years in the studies. All data are reported for the safety analysis set (SAS), which comprised patients who passed screening and were assigned to a treatment group or regimen in the INT study, or were enrolled and have received ≥1 dose of rAHF since study enrollment in the GER study. Results: At the time of analysis, the INT study SAS comprised 707 patients, 156 of whom had received ≥5 years of rAHF treatment during the study. The GER study SAS comprised 382 patients, 231 of whom had received ≥5 years of rAHF treatment. Average Gilbert scores (all joints) were consistently low (years 1-6: median 0-1.0; mean 0-1.3) for both children aged 2 to <12 years and adolescents aged 12 to <18 years receiving rAHF prophylaxis within both studies. In the INT study, average Gilbert scores were lower with prophylaxis than with OD therapy in adults (aged ≥18 years) throughout the observation period (years 1-6: median: 0.9-1.4 [n=8-25] vs 1.4-6.3 [n=2-8], respectively; mean: 1.4-2.2 vs 2.1-6.3; respectively); significant differences (P<0.05) between mean values were observed for years 3, 4, and 6. In the GER study, average Gilbert scores were slightly higher with prophylaxis than with OD in adults (years 1-6: median: 0.7-2.2 [n=12-37] vs 0.3-1.4 [n=2-15], respectively; mean: 1.0-2.7 vs 0.5-2.2, respectively; P-values not available). In the INT study, ABRs were consistently lower in patients receiving rAHF prophylaxis than in those receiving rAHF OD, irrespective of disease severity (Table). A similar trend was observed in the GER study in patients with severe HA, whereas ABRs were similar for both treatment regimens in patients with moderate HA. In both studies, greater proportions of patients with moderate or severe HA receiving rAHF prophylaxis had 0 bleeds than those receiving rAHF OD (Table). In the INT study, 842 AEs were reported in 116/156 (74.4%) patients, including 2 treatment-related serious AEs in 2 (1.3%) patients. In the GER study, 1321 AEs were reported in 197/231 (85.3%) patients, including 29 treatment-related serious AEs in 14 (6.1%) patients. Conclusions: These findings in patients receiving rAHF for ≥5 years in a real-world setting corroborate previous data on the long-term efficacy and tolerability of rAHF in patients with moderate or severe HA. rAHF demonstrated effectiveness in maintaining joint health (as measured by Gilbert scores) in adult patients. Table Disclosures Tsakiris: Roche: Research Funding; Shire, a Takeda company: Research Funding; Sobi: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding. Oldenburg:Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Klamroth:Pfizer: Consultancy, Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Guillet:CSL Behring: Research Funding, Speakers Bureau; Octapharma: Research Funding; Bayer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Speakers Bureau; Roche-Chugai: Consultancy, Speakers Bureau. Khair:Shire, a Takeda company: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Baxalta/Shire, Takeda companies: Research Funding. Huth-Kühne:Bayer: Consultancy; CSL Behring: Consultancy; Shire, a Takeda company: Consultancy; Sobi: Consultancy. Kurnik:Sobi: Consultancy, Research Funding; Biotest: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau. Regensburger:Takeda Pharma Vertrieb GmbH & Co. KG: Current Employment, Current equity holder in publicly-traded company. Botha:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Fernandez:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Tang:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Ozelo:Pfizer: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau.

Download Full-text

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

Blood ◽

10.1182/blood-2020-139298 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 23-24

Author(s):

Cedric Hermans ◽

Claude Négrier ◽

Pål A Holme ◽

Carmen Escuriola ◽

Ana R Cid ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Interim Analysis ◽

Research Funding ◽

Hemophilia A ◽

Outcome Study ◽

Publicly Traded ◽

On Demand ◽

The Past

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

Download Full-text

Patient (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5042 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5042-5042 ◽

Cited By ~ 1

Author(s):

Celestia S. Higano ◽

Shawn H. Zimberg ◽

Sabina Dizdarevic ◽

Lauren Christine Harshman ◽

John Logue ◽

...

Keyword(s):

Clinical Practice ◽

Observational Study ◽

Interim Analysis ◽

Routine Clinical Practice ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Observation Methods ◽

Short And Long Term ◽

Grade 3

5042 Background: Ra-223, a targeted alpha therapy, prolonged survival with good safety in metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial. REASSURE will evaluate Ra-223 short- and long-term safety in routine clinical practice settings. This is the first planned interim analysis (median 7 mo observation). Methods: This global, prospective, single-arm, observational study enrolled pts with mCRPC with bone metastases (mets) for whom Ra-223 therapy was planned. Follow-up will continue up to 7 years after last Ra-223 dose. Results: 1106 pts (437 N. America, 665 Europe, 4 not recorded) enrolled from 2 Sep 2014 to 22 Sep 2016. Baseline data are available from 583 pts receiving 1st- (1L), 2nd- (2L), or ≥3rd-line (≥3L) Ra-223 for mCRPC(Table). The majority of pts (n=369, 63%) completed 5–6 doses (1L, 70%; 2L, 64%; ≥3L, 49%); median 6 doses (1L,6; 2L, 6; ≥3L, 4). Treatment-emergent drug-related AEs occurred in 215 pts (37%). Post-treatment grade 3/4 thrombocytopenia occurred in 14 pts (2.4%) and anemia in 45 (7.7%). Conclusions: In routine clinical practice, Ra-223 was associated with no short-term safety concerns and appeared to be used in pts with less advanced mCRPC than in ALSYMPCA. The majority of pts on 1L/2L Ra-223 therapy received 5–6 doses. Ra-223 was often used with abiraterone or enzalutamide, but not chemotherapy. The next interim analysis in 2019 will report long-term safety and outcomes on all pts. Clinical trial information: NCT02141438. [Table: see text]

Download Full-text

Real-World Efficacy of Venetoclax-Based Regimens in Patients with Chronic Lymphocytic Leukemia in Israel: A Multicenter Prospective Study

Blood ◽

10.1182/blood-2021-146504 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3727-3727

Author(s):

Yair Herishanu ◽

Neta Goldschmidt ◽

Gilad Itchaki ◽

Itai Levi ◽

Ariel Aviv ◽

...

Keyword(s):

Real World ◽

Interim Analysis ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Publicly Traded ◽

Phase Iii Clinical Trials ◽

Medical Centers ◽

Grade 3

Abstract Background: The BCL-2 inhibitor venetoclax in combination with an anti-CD20 monoclonal antibody (rituximab or obinutuzumab) has demonstrated superior outcomes and manageable safety as compared to chemo-immunotherapy in phase III clinical trials for chronic lymphocytic leukemia (CLL). Moreover, venetoclax-based regimens induced high rates of undetectable minimal residual disease (uMRD). Prospective data on the effectiveness of venetoclax-based regimens specifically with regard to achieving uMRD in a real-world setting are still lacking. Here we report the first interim analysis for efficacy and safety of an ongoing nationwide real-world study of venetoclax based therapy for CLL/small lymphocytic lymphoma (SLL). Method: A prospective observational nationwide multicenter study. Treatment-naïve (TN) and relapsed/refractory (R/R) CLL/SLL patients were enrolled in 13 medical centers in Israel. The primary endpoint was clinical response, per physician assessment 12-months after the initiation of venetoclax treatment. Key secondary endpoints included progression free survival (PFS), overall survival (OS) and uMRD as assessed at a central laboratory by 8-color flow-cytometry. Results: Between February 10, 2019, and Jun 17, 2021 (data cut), 199 CLL/SLL patients were enrolled from 13 medical centers in Israel to receive venetoclax based therapy. The study included 83 TN and 116 R/R evaluable CLL/SLL patients with a median age of 69 years (range, 34-85) and 70.5 years (range, 25-91), respectively (Table 1). R/R patients had received a median of one prior therapy with a range up to 8, of these patients 60 (51.7%) were previously treated with a B-cell receptor inhibitor (BCRi) including ibrutinib in 52 (44.8%) and idelalisib in combination with rituximab in 6 (5.2%). TN patients had been treated with venetoclax in combination with obinutuzumab (92.8%) or rituximab (4.8%) and R/R patients received either venetoclax with rituximab (60.3%) or obinutuzumab (9.5%), venetoclax monotherapy (25.8%) or triple therapy with venetoclax, rituximab and ibrutinib in 5 (4.3%). Dose escalation of venetoclax to the recommended dose of 400 mg daily was achieved in 80.7% (n=67) of TN and 81% (n=94) of R/R patients. The median duration of ramp-up was 38 and 42 days in TN and R\R patients, respectively. Prior to therapy, tumor lysis syndrome (TLS) risk was considered high in 12% and 29.3% of TN and R/R patients, respectively (Table 1). Laboratory TLS occurred in one TN patient and 4 R/R patients, whereas 3 of the R/R patients experienced clinical TLS. Nineteen TN and 75 R/R patients had a follow-up of at least 12 months or discontinued study prematurely. The 12-month overall response rate (ORR) for TN and R/R patients was 89.5% [complete response (CR) 13 (68.4%), partial response (PR) 4 (21.1%)] and 73.3% [CR 37 (49.3%), PR 18 (24%)], respectively. In the R/R cohort, the 12-month ORR among assessed patients was 67.6% (25/37) in BCRi-exposed versus 85.7% (30/35) in BCRi-naïve patients. At 12 months, peripheral blood uMRD (<0.01%) was achieved in 12 out of 14 (85.7%) TN and 26 out of 38 (68.4%) R/R evaluated patients. At a median follow-up of 5.1 months (range, 0.5-15.6) for TN and 10.1 months (range, 0-25.7) for R/R patients, the median PFS and OS, for both cohorts have not been reached. The estimated 12-month PFS was 90.9% for TN and 81.1% for R/R patients. For R/R patients with prior exposure to BCRi, the estimated 12-month PFS was 69.6% versus 94.8% in BCRi-naïve patients (figure 1). Grade ≥3 adverse events (AEs) were reported in 34.9% of TN patients and 43.9% R/R patients. The most frequent grade ≥3 AEs documented were neutropenia (TN: 19.2% and R/R 17.2%), infections (TN: 4.8% and R/R: 21.5%) and febrile neutropenia (TN: 2.4% and in R/R: 2.6%). COVID-19 occurred in 7 patients including one death. At the time of data cut, 10 deaths occurred, one TN and 9 R/R patients. Causes for death included infections (5 patients), disease progression (2 patients), acute myeloid leukemia/ myelodysplastic syndrome (2 patients) and a soft-tissue sarcoma (1 patient). Conclusions: This first interim analysis of our ongoing prospective real-world study of venetoclax-based treatment for TN and R/R CLL/SLL, demonstrates high efficacy together with a high proportion of undetectable MRD levels and a favorable toxicity profile. These efficacy results are comparable to those reported in previous Phase III clinical trials for CLL, with no new safety signals. Figure 1 Figure 1. Disclosures Herishanu: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; AstraZeneca: Honoraria. Goldschmidt: AbbVie: Consultancy, Research Funding. Itchaki: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Levi: AbbVie: Consultancy, Research Funding. Aviv: AbbVie: Honoraria, Research Funding. Fineman: AbbVie: Research Funding. Dally: AbbVie: Honoraria, Research Funding. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Abadi: AbbVie: Honoraria, Research Funding. Shvidel: AbbVie: Honoraria, Research Funding. Braester: AbbVie: Honoraria, Research Funding. Cohen: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.

Download Full-text

Four-Year Interim Analysis of Miroir, a French Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2019-124484 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1836-1836

Author(s):

Olivier Decaux ◽

Margaret Macro ◽

Sophie Gourgou ◽

Florence Lachenal ◽

Caroline Bureau Lenoir ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Practice ◽

Board Of Directors ◽

Interim Analysis ◽

Research Funding ◽

Routine Clinical Practice ◽

Interventional Study ◽

Real World Data ◽

Advisory Committees ◽

Refractory Multiple Myeloma

BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged < 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged < 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx (< or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.

Download Full-text

Characteristics of a Comprehensive, Continuously Updated Longitudinal Database for Multiple Myeloma

Blood ◽

10.1182/blood-2021-148399 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4969-4969

Author(s):

C. Anthony Blau ◽

Grace Nam ◽

Leena Chhun ◽

Cheng Zheng ◽

Jayne Piboonvaranggoon ◽

...

Keyword(s):

Multiple Myeloma ◽

Disease Control ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Disease Stage ◽

Publicly Traded ◽

Advisory Committees ◽

Multi Agent

Abstract Introduction: Despite the availability of many effective agents, multiple myeloma is characterized by repeated cycles of treatment response and relapse, and remains incurable in almost all patients. Efforts to optimize treatment are complicated by variation in disease biology and by the combinatorial complexity inherent in assembling, sequencing and administering multi-agent regimens. Determining which strategies provide maximal therapeutic benefit requires deploying a variety of multi-agent regimens in a range of settings and assessing long-term outcomes; information that cannot be readily discerned from clinical trials. Here we present results from a real-world database that comprehensively tracks all treatments and responses in patients with multiple myeloma. Methods: Since March 2017, All4Cure has hosted an online platform for patients with multiple myeloma, clinicians and researchers that has been initially focused in the Pacific Northwest. Medical records from consenting patients are collected and information regarding all treatments and responses graphically displayed on their de-identified dashboards. A discussion panel allows for asynchronous communication between members of All4Cure's community of patients, clinicians and researchers (currently numbering over 1600 participants). There is no charge to patients who participate in All4Cure, and clinicians and researchers are neither charged nor paid for their participation. A summarized real-world database describes the lines of therapy that each patient has received, treatment start and stop dates, and responses in accordance with International Myeloma Working Group (IMWG) criteria. Results: The overall profile of patients with multiple myeloma enrolled in All4Cure (N=555) was benchmarked against myeloma patients from the National Program of Cancer Registries (NPCR) (diagnosis year 2017; N=25,895). Patients in all 50 States and D.C. were included in the comparison, and those with monoclonal gammopathy of undetermined significance (MGUS) were not considered. Myeloma patients enrolled in All4Cure are younger at diagnosis or start of treatment (median 61 versus between 65 and 69), more likely to be white (90.3% versus 73.5%), and more likely to reside in Washington State (41.2% versus 2%) compared to the NPCR cohort, reflecting participation influenced by geographic location as described above. After enrollment, All4Cure patients are followed longitudinally throughout the entirety of their disease course, with fewer than 2% having been lost to follow up. To gain insights uniquely available from the All4Cure database and to inform the future direction for our research, we focus our exploratory data analysis on the All4Cure cohort of patients who started treatment in June 2015 or later (N=299). Despite the relatively recent start of the All4Cure database, this timeframe allows up to 6 years of observation following the start of treatment, since the survival rates for the first 1-2 years of treatment are generally very high. Consistent with prior knowledge, increasing age and disease stage are associated with increased morality, as are high-risk cytogenetics such as 17p-, t(4:14) and t(14;16). We further explored the potential impact of early lines of therapy on long-term disease control. While the current literature is mixed on the merits of aggressive treatments in early lines of therapy in terms of overall survival, insights from our data suggest that more aggressive front-line therapies (such as SCT) are associated with improved disease control over time, although this is evolving with the impact of novel therapies and in particular the use of triplet and now quadruplet induction regimens and adapting treatment to achieve measurable residual disease (MRD) negativity. Conclusions: Even with the current limitations regarding the size and representativeness of All4Cure's database, these preliminary results support the validity of this approach for gaining insight into the treatments and outcomes of patients with multiple myeloma in real-world settings. Disclosures Blau: Oncopeptides: Other: Oncopeptides is an All4Cure customer. Blau: All4Cure: Current equity holder in publicly-traded company. Richter: Tisch Cancer Institute: Icahn School of Medicine at Mount Sinai: Current Employment; Janssen, Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive biotechnologies: Speakers Bureau; BMS, Karyopharm, Antengene: Membership on an entity's Board of Directors or advisory committees. Bensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. Richardson: Secura Bio: Consultancy; Protocol Intelligence: Consultancy; Sanofi: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; AbbVie: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: 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; Pfizer: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Real-World Effectiveness and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) in Previously Treated Patients with Hemophilia A (HEM-POWR): Online Patient Portal and LIFE-ACTIVE Sub-Study

Blood ◽

10.1182/blood-2019-128140 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4943-4943

Author(s):

Johannes Oldenburg ◽

María Teresa Alvarez Román ◽

Giancarlo Castaman ◽

Maissaa Janbain ◽

Tadashi Matsushita ◽

...

Keyword(s):

Study Design ◽

Real World ◽

Research Funding ◽

Hemophilia A ◽

Patient Portal ◽

The Real ◽

Patient Reported ◽

Previously Treated Patients ◽

Previously Treated

Background and Rationale: BAY 94-9027 (damoctocog alfa pegol) is a site-specifically PEGylated B-domain deleted recombinant factor VIII (FVIII) with an extended half-life, approved for prophylaxis or treatment of bleeds in previously treated patients (PTPs) aged ≥12 with hemophilia A. The efficacy and safety of BAY 94-9027 was demonstrated in two phase II/III clinical studies in PTPs with severe hemophilia A, however, real-world data are still being gathered. The aim of the HEM-POWR study is to assess the effectiveness and long-term safety of BAY 94-9027 in the real-world clinical setting. Patients will be introduced to an online patient portal that provides study information as well as access to eDiaries and electronic patient-reported outcomes (ePROs) to patients to facilitate retention over the duration of the study. Patients will also be given the opportunity to participate in LIFE-ACTIVE, a sub-study analyzing the relationship between the patients' regular daily activity and the efficacy parameters collected during HEM-POWR. Here we present the features of the patient portal and describe the LIFE-ACTIVE sub-study design. Study Design and Methods: HEM-POWR (NCT03932201) is a multinational, multicenter, non-interventional, open-label, prospective, phase IV, cohort study. It aims to enroll ≥200 PTPs with hemophilia A receiving BAY 94-9027 (on-demand, prophylaxis, or intermittent prophylaxis [as per local label]). Key exclusion criteria are presence or history of FVIII inhibitor (≥0.6 Bethesda units), diagnosis of any bleeding or coagulation disorder other than hemophilia A, or treatment with immune tolerance induction at enrollment. The primary objective of HEM-POWR is to assess the effectiveness of prophylaxis with BAY 94-9027 in the real-world setting through the collection of total bleeding events and analysis of annualized bleeding rate. Secondary objectives include long-term safety, joint health, location and number of target joints, hemostasis during surgery and PROs. Patient enrollment, adherence and retention can be difficult in observational hemophilia studies. The patient portal for this study aims to overcome these challenges by providing study- and product-related information. It also aims to lessen the burden for patients in the study by providing e-solutions to collect their study data, including the ability to complete the study diary, and PRO measures online. The portal also includes videos explaining the study and study procedures, and is country-customized with links to relevant websites. Patients participating in LIFE-ACTIVE will be asked to wear an ActiGraph CP Insight activity-tracking smart watch continually for four 30-day periods, at their initial visit and then at months 12, 24 and 36. Measurements recorded will include physical activity intensity and duration, general mobility, and sleep quality and duration. All data will be transferred to a secure, cloud-based system and patients will not be aware of the values measured by the device. Participating countries include, but may not be limited to Austria, Belgium/Luxemburg, Canada, Colombia, Finland, Germany, Greece, Italy, Japan, Netherlands, Portugal, Saudi Arabia, Denmark, Norway, Sweden, Slovenia, Spain, Switzerland, Taiwan, and USA. The study will run from 2019 until 2025, with an observation period of ≥60 months. Disclosures Oldenburg: Octapharma: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Takeda (Shire): Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; Swedish Orphan Biovitrum: Consultancy, Speakers Bureau. Alvarez Román:CSL Behring: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Sobi: Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Shire (Takeda): Research Funding, Speakers Bureau. Castaman:Shire: Speakers Bureau; Uniqure Kedrion: Speakers Bureau; Pfizer: Research Funding; CSL Behring: Research Funding, Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sobi: Research Funding, Speakers Bureau. Janbain:Shire (Vonvendi): Speakers Bureau; Genentech: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Shire: Consultancy, Honoraria; HTRS-MRA (Bioverativ Sanofi): Research Funding. Matsushita:uniQure: Consultancy, Honoraria; CSL: Consultancy, Honoraria; Bioverative: Research Funding; Pfizer: Consultancy, Honoraria; KM biologists: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria. Meijer:Sanquin: Research Funding; Pfizer, Sanquin, Uniqure: Research Funding; Uniqure, BMS, Aspen, Boehringer Ingelheim, Sanquin, Bayer: Consultancy, Honoraria; Bayer: Research Funding. Sanabria:Bayer: Employment. Reding:Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Biomarin: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

Download Full-text

Impact of Hemophilia a Inhibitor on Joint Health and Health-Related Quality of Life from the Hemophilia Utilization Group Studies Part VIII in the U.S

Blood ◽

10.1182/blood-2020-142947 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Megan M. Ullman ◽

Marilyn J Manco-Johnson ◽

Jonathan C. Roberts ◽

Nicole Crook ◽

Rahul Khairnar ◽

...

Keyword(s):

Research Funding ◽

Hemophilia A ◽

Publicly Traded ◽

Active Inhibitor ◽

Adult Participants ◽

Younger Age ◽

Related Quality ◽

Joint Health ◽

Health Related

Introduction: Persons with hemophilia A (PwHA) and Factor VIII inhibitors experience significant economic burden associated with high treatment costs and compromised physical and psychosocial health. Few studies have compared burden of illness for PwHA with active inhibitors to those with tolerized or no inhibitor. We describe clinical and treatment outcomes, and health-related quality of life (HRQoL) in PwHA with and without inhibitors using the Hemophilia Utilization Group Studies Part VIII (HUGS VIII) baseline cross-sectional data. Methods: HUGS VIII prospectively examines the cost and burden of hemophilia care, including HRQoL, arthropathy, and psychosocial impact in PwHA aged ≥2 years. The study enrolled PwHA with inhibitors and without inhibitor at a 1:2 ratio. Participants were classified to three groups: 1) active inhibitor (FVIII≥1.0 Bethesda Units within six months of data extraction), 2) presumably tolerized inhibitor (history of immune tolerance induction, ITI, and using factor VIII for prophylaxis), and 3) no inhibitor. Parents/adult participants completed a standardized interview at enrollment (baseline) to collect sociodemographic and clinical data, self-reported pain, joint health, and HRQoL measured by the EQ-5D-3L. Clinical chart review documented hemophilic severity, inhibitor level and treatment regimen. Associations between participants' characteristics and inhibitor status were assessed using Chi-square tests. Results: Data from 73 participants with complete baseline information were analyzed. Mean age was 24.8 (standard deviation (SD)=14.1) years, 65.8% were adults, 87.7% had severe hemophilia A, and 87.1% self-reported receiving prophylactic treatment. The three groups of participants were: non-inhibitor (n=42, 57.5%); tolerized inhibitor (n=23, 31.5%); and active inhibitor (n=8, 11.0%). Mean age among the tolerized inhibitor group was significantly younger (17.3, SD=9.3 years) than active inhibitor (22.6, SD=20.4) or non-inhibitor groups (29.3, SD=13.3), p=0.02. Among individuals with inhibitors, 78.6% had undergone ITI which was successful in 72.2%. Adult participants/parents in the active inhibitor group reported a lower rate of full-time employment (42.9%) compared to the non-inhibitor (58.5%) or tolerized inhibitor (55.7%) groups, p=0.03. Compared to those without inhibitors or tolerized inhibitors, those with active inhibitors showed lower HRQoL with lower covariates adjusted mean EQ-5D Visual Analogue Scale (73.1 vs. 83.6, 80.2, P=0.21) or index score (0.80 vs. 0.87, 0.88, P=0.57). Participants with active inhibitors and those without inhibitors were more likely to report having joint pain (85.7%, 75.6% non-inhibitors, vs. 59.1% tolerized inhibitors, p=0.26), or very stiff joints upon arising (71.4%, 73.2%, vs. 27.3%, p=0.002) or during the day (71.4%, 63.4% vs. 27.3%, p=0.01) than those with a tolerized inhibitor, likely due to younger age and earlier institution of long-term effective prophylaxis after ITI. Conclusions: While the study is limited to a small sample with a skew to younger age in persons with tolerized inhibitors, preliminary analyses indicate that individuals with active inhibitors experienced greater negative impacts on employment and HRQoL than PwHA with no or tolerized inhibitors. Younger persons with tolerized inhibitors showed better joint health (less pain, stiffness) than older persons with active or no inhibitor. Future research using longitudinal data on these participants will examine whether individuals in the tolerized inhibitor group with successful ITI continue with long-term prophylaxis and achieve positive joint health outcomes. Disclosures Roberts: uniQure: Consultancy; Takeda: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau. Khairnar:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Wu:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Carrasco:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Curtis:Bayer: Consultancy; USC Hemophilia Utilization Group Study (HUGS): Consultancy; Novo Nordisk: Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy. Tran:Bioverativ: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Takeda: Consultancy. Nichol:Pfizer: Research Funding; Octapharma: Research Funding; CSL Behring: Research Funding; Global Blood Therapeutics: Research Funding; Baxalta US Inc., Bannockburn, IL (a Takeda Company): Research Funding; Genentech Inc.: Research Funding.

Download Full-text

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

Blood ◽

10.1182/blood-2021-148378 ◽

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.

Download Full-text