ANALYSIS OF SUSTAINED HEMATOLOGIC IMPROVEMENT WITH IBRUTINIB TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA
Author(s): ,
William Wierda
Affiliations:
University of Texas MD Anderson Cancer Center,Houston, TX, United States,United States
,
John Byrd
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus, OH, United States,United States
,
Asher Chanan-Khan
Affiliations:
Mayo Clinic Cancer Center,Jacksonville, FL,United States
,
Jan Burger
Affiliations:
University of Texas MD Anderson Cancer Center,Houston, TX, United States,United States
,
Paula Cramer
Affiliations:
University of Cologne, German CLL Study Group,Cologne,Germany
,
Alessandra Tedeschi
Affiliations:
ASST Grande Ospedale Metropolitano Niguarda,Milan,Italy
,
Jennifer Brown
Affiliations:
Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute,Boston, MA, United States,United States
,
Paul Barr
Affiliations:
Wilmot Cancer Institute, University of Rochester Cancer Center,Rochester, NY, United States,United States
,
Susan O'Brien
Affiliations:
University of California Irvine, Chao Family Comprehensive Cancer Center,Orange, CA,United States
,
Fatih Demirkan
Affiliations:
Dokuz Eylul University,Izmir,Turkey
,
Jacqueline Barrientos
Affiliations:
Hofstra Northwell School of Medicine,Hempstead, NY,United States
,
Graeme Fraser
Affiliations:
Juravinski Cancer Centre, McMaster University,Hamilton, ON,Canada
,
Tadeusz Robak
Affiliations:
Medical University of Lodz,Lodz,Poland
,
Charles Phelps
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ, United States,United States
,
Angela Howes
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ, United States,United States
,
Cathy Zhou
Affiliations:
Pharmacyclics, LLC, an AbbVie Company,Sunnyvale, CA,United States
,
James Dean
Affiliations:
Pharmacyclics, LLC, an AbbVie Company,Sunnyvale, CA,United States
,
Danelle James
Affiliations:
Pharmacyclics, LLC, an AbbVie Company,Sunnyvale, CA,United States
,
Peter Hillmen
Affiliations:
The Leeds Teaching Hospitals, St. James Institute of Oncology,Leeds,United Kingdom
,
Thomas Kipps
Affiliations:
University of California San Diego, Moores Cancer Center,La Jolla, CA,United States
Michael Hallek
Affiliations:
University of Cologne, German CLL Study Group,Cologne,Germany
EHA Library. Wierda W. Jun 15, 2018; 214825; PF352
Dr. William Wierda
Dr. William Wierda
Contributions
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Abstract

Abstract: PF352

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
Ibrutinib (ibr), a first-in-class, once-daily oral inhibitor of Bruton’s tyrosine kinase.  Ibrutinib as a single agent is indicated for treatment of patients (pts) with chronic lymphocytic leukemia (CLL) by EMEA and for CLL/small lymphocytic leukemia (SLL) by US FDA and allows for treatment without chemotherapy. Superior efficacy of ibr over comparator drugs was demonstrated in clinical studies with ibr in CLL/SLL (Byrd, NEJM, 2014; Burger, NEJM, 2015; Chanan-Khan, Lancet Oncol, 2016).

Aims
To assess sustained hematologic improvement (SHI) with a side-by-side presentation of three phase 3 clinical studies with ibr vs. comparator arm as first line treatment in pts with CLL/SLL or in pts with relapsed/refractory (R/R) CLL/SLL.

Methods
Ibr 420 mg daily was given until progressive disease or unacceptable toxicity in the RESONATE (PCYC-1112) and RESONATE-2 (PCYC-1115/1116) studies and in combination with bendamustine plus rituximab (BR) in the HELIOS study (CLL3001). Comparator/combination agents were of fixed duration. In the RESONATE study, pts with R/R CLL/SLL received up to 6 cycles of ofatumumab (ofa; Byrd, NEJM, 2014). In RESONATE-2, treatment naïve pts aged ≥65 y with CLL/SLL received up to 12 cycles of chlorambucil (clb; Burger, NEJM, 2015). In the HELIOS study, pts with R/R CLL/SLL received up to 6 cycles of combined placebo and BR (Chanan-Khan, Lancet Oncol, 2016). All patients provided written informed consent. SHI was compared using Fisher’s exact test and was defined as ≥56 days with: 1) platelet count >100 x 109/L if baseline ≤100 x 109/L or increase ≥50% over baseline; or 2) hemoglobin >11 g/dL if baseline ≤11 g/dL or increase ≥2 g/dL over baseline (in pts without blood transfusion or growth factor support).

Results
The analysis included a total of 1238 pts (391 RESONATE, 269 RESONATE-2, 578 HELIOS). Compared to respective comparator arms, ibr treatment resulted in sustained increase in hemoglobin for pts with baseline anemia (RESONATE: 80% vs. 44%, P<0.0001; RESONATE-2: 90% vs. 45%, P<0.0001; HELIOS: 74% vs. 65%, P=0.2528) or sustained increase in platelets for pts with baseline thrombocytopenia (RESONATE: 85% vs. 20%, P<0.0001; RESONATE-2: 83% vs. 46%, P=0.0032; HELIOS: 69% vs. 59%; P=0.1935) (Figure). The rates of SHI were improved with ibr treatment vs. comparators across specified high-risk genomic subgroups (del11q, complex karyotype, unmutated IGHV and trisomy 12) in all three studies and in del17p pts, which were enrolled in the RESONATE study only. Pts with SHI had improved progression-free survival (PFS) with ibr vs. comparators at 36 months in all studies (Figure, RESONATE: 68% vs. 7%; RESONATE-2: 80% vs. 32%; HELIOS: 77% vs. 21%) as well as overall response rates (ORR; RESONATE: 97% vs. 29%; RESONATE-2: 95% vs. 50%; HELIOS: 95% vs. 76%). Improvement in fatigue was observed for all patients who achieved SHI on RESONATE and RESONATE-2. In long term follow-up, grade 3-4 hematologic adverse event (AE) rates overall and in pts with SHI continued to appear favorable for ibr (median treatment and AE collection periods up to 8-fold longer in ibr vs. comparator arms).

Conclusion
Analyses showed that single-agent and combination treatment with ibr resulted in a high frequency of SHI in hemoglobin and platelet levels for both first-line and R/R pts vs. comparators. ORR and PFS improvements with ibr, including in pts with SHI benefit, were maintained vs. comparators. Over a median treatment duration of 34-41 months, the rates of severe hematologic AEs continue to remain low for patients treated with ibr.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Anemia, Chronic Lymphocytic Leukemia, Targeted therapy, Thrombocytopenia

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