Konference: 2015 51th ASCO Annual Meeting - účast ČR
Kategorie:
Maligní lymfomy a leukémie
Téma: Leukemia, Myelodysplasia, and Transplantation
Číslo abstraktu: LBA7005
Autoři: M.D. Asher Alban Akmal Chanan-Khan; MD Paula Cramer; prof. MUDr. Fatih Demirkan; Dr. Graeme Fraser; Dr. Rodrigo Santucci Silva; MD Halyna Pylypenko; M.D. Sebastian Grosicki; MD Ann Janssens; M.D. Alexander S. Pristupa, Ph.D.; prof. MUDr. Jiří Mayer, CSc.; Marie-Sarah Dilhuydy; Dr. Javier Loscertales; Dr. Nancy L. Bartlett, MD; Dr. Abraham Avigdor; prof. Simon A. Rule; Steven Sun; Michelle Mahler; Mariya Salman; Angela J. Howes; Prof. MD Michael Hallek
Background: The phase III HELIOS study evaluated
the first-in-class, oral covalent BTK inhibitor ibrutinib in
combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in
patients (pts) with previously treated CLL/SLL. The preplanned
interim analysis reported here showed that the primary end point
was met, upon which the IDMC recommended unblinding the study.
Methods: Pts received BR ( ≤ 6 cycles) and were
randomized 1:1 to ibr (420 mg daily) or plb. Purine analog
refractoriness was a stratification factor. Pts with del17p ( >
20% of cells) were excluded. Primary end point was independent
review committee (IRC)-assessed progression-free survival (PFS).
Secondary end points included overall survival (OS) and overall
response rate (ORR) per IRC.Results: 578 pts were
randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV;
median 2 prior therapies. 6 cycles of BR were completed in 83% and
78% of pts in the ibr and plb arms, respectively. At a median
follow-up of 17.2 months, IRC-assessed PFS was significantly longer
with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR:
0.203, 95% CI: 0.150-0.276, P< 0.0001); PFS results
were consistent across high-risk subgroups. ORR and CR/CRi rates
were 82.7% vs 67.8% (P< 0.0001) and 10.4% vs 2.8%.
Median OS was not reached. 90 pts (31%) in the BR+plb arm with
confirmed PD crossed over to receive ibr, as permitted per the
protocol. Incidence of most AEs was similar between arms. The most
common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2%
vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs
were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each
arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%,
and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue)
was improved with BR+ibr vs BR+plb. Conclusions:
The addition of ibr to BR reduced the risk of progression or death
by 80% compared with BR+plb. ORR was also significantly improved.
Safety of BR+ibr was consistent with the known profiles for BR and
ibr. The data further support ibr as an important treatment option
for pts with previously treated CLL/SLL. Clinical trial
information: EudraCT No. 2012-000600-15; UTN No.
U1111-1135-3745.
Citation:
J Clin Oncol 33, 2015 (suppl; abstr LBA7005)
www.asco.org (též
presentace, slide)
Datum přednesení příspěvku: 30. 5. 2015