Konference: 2015 57th ASH Annual Meeting - účast ČR
Kategorie: Maligní lymfomy a leukémie
Téma: 642. CLL: Therapy, excluding Transplantation: Upfront CLL Therapy Excluding Transplantation
Číslo abstraktu: 495
Autoři: MD Alessandra Tedeschi; MD Paul M. Barr; MD Tadeusz Robak, PhD.; Dr. Carolyn Owen; M.D. Paolo Ghia, Ph.D.; MD Osnat Bairey; Peter Hillmen, M.B. ChB, Ph.D.; Dr. Nancy L. Bartlett, MD; Dr. Jianyong Li (Jian-Yong Li), Ph.D.; M.D. David Simpson, FRACP, FRCPA, MBChB; M.D. Sebastian Grosicki; Prof. Stephen Devereux, FRCP, FRCPath, PhD; Helen McCarthy, FRCP, FRCPath, PhD; MD Steven Coutre; MD Hang Quach; MD Gianluca Gaidano, PhD; MD Zvenyslava Maslyak; MD Don A. Stevens; MD Ann Janssens; MD Fritz C. Offner, PhD; prof. MUDr. Jiří Mayer, CSc.; Prof. Dr. Michael O'Dwyer; MD Andrzej Hellmann, Ph.D.; M.D. Anna Schuh, Ph.D.; MD Tanya Siddiqi; MD Aaron Polliack; Dr. Constantine S. Tam, MBBS; MD Michael Keating, MBBS; Deepali Suri, MS; Cathy Zhou, MS; Fong Clow, ScD; MD Lori Styles; MD Danelle F. James, MAS; MD Thomas J. Kipps, PhD; MD Jan A. Burger, Ph.D.
Methods: Pts aged ≥65 years with treatment-naïve CLL/SLL were randomized 1:1 to receive 420 mg ibr daily until progression or clb 0.5 mg/kg (up to maximum of 0.8 mg/kg) on days 1 and 15 of a 28-day cycle for up to 12 cycles. Pts with del17p were excluded. Primary endpoint was independent review committee (IRC)-assessed PFS periwCLL 2008 criteria, with 2012 clarification for treatment-related lymphocytosis. Secondary endpoints included overall survival (OS), ORR, event-free survival (EFS), rate of hematologic improvement, and safety. Pts with IRC-confirmed progression could transfer to an extension study where next-line therapy (including ibr) could be initiated if they had an iwCLL indication for treatment.
Results: Among 269 pts enrolled, median age was 73 years (70% ≥70 years). Baseline characteristics were balanced between arms; 45% had advanced Rai stage, 20% had del11q, and 69% had comorbidities at baseline including CIRS score >6, reduced creatinine clearance, or ECOG status of 2. For pts treated with clb, 40% completed 12 cycles of therapy (mean dose 0.6 mg/kg). At a median follow-up of 18.4 months (mos), ibr significantly prolonged IRC-assessed PFS vs clb (median not reached [NR] vs 18.9 mos; HR 0.16, 95% CI 0.09-0.28, P<0.0001); this was consistent within subgroups including age ≥70 years, del11q, and unmutated IGHV. As assessed by investigator, ibrreduced the risk of progression or death by 91% (HR 0.09; 95% CI, 0.04-0.17; P<0.0001; Figure 1A), with an 18-mo PFS of 93.9% vs 44.8%. Ibr significantly prolonged OS vs clb (median NR for either arm; HR 0.16, 95% CI 0.05-0.56, P=0.0010; Figure 1B); 24-mo OS was 97.8% vs 85.3%, respectively. Three deaths occurred on the ibr arm vs 17 deaths on clb arm. The IRC-assessed ORR was 86.0% with ibr (4.4% CR/CRi) vs 35.3% with clb (1.5% CR/CRi). ORR with ibr was higher than clb at all evaluated time points; at 8 mos, ORR was 84% and 31%, respectively. Investigator-assessed ORR was 90.4% (9.6% CR/CRi) vs 35.3% (4.5% CR/CRi), respectively. Median EFS was also prolonged withibr (NR vs 12 mos; HR 0.17, 95% CI 0.10-0.26; P<0.0001). A ≥50% reduction in lymph node burden was observed in 91.2% vs 36.8% (P<0.0001), and reduction in spleen enlargement in 75.7% vs 39.1% (P<0.0001), for ibr and clb, respectively. Rates of sustained hematologic improvements were significantly higher with ibr vs clb, including in pts with baseline anemia (84% vs 45%; P<0.0001) or thrombocytopenia (77% vs 43%; P=0.0054). Median duration of treatment was 17.4 mos with ibr and 7.1 mos with clb. Most frequent (≥20% of pts) adverse events (AEs) with ibrincluded diarrhea, fatigue, cough and nausea. Most frequent AEs with clb included nausea, fatigue, neutropenia, anemia and vomiting. AEs leading to treatment discontinuation were less frequent with ibr (9% vs 23%). Atrial fibrillation occurred in 6% (6 pts grade 2 and 2 pts grade 3) with ibr and 1% with clb. Hypertension was noted more frequently on ibr, but was limited to grade 1-3 and managed without ibr dose modification or discontinuation. Major hemorrhage occurred in 4% (1 pt grade 2, 4 pts grade 3, 1 pt grade 4) with ibr over median follow-up of approximately 1.5 years, and in 2% with clb. At the time of study closure, 87% of pts randomized to ibr continue to receive ibr.
Treatment with single-agent ibr was superior
to clb in terms of PFS, OS, ORR, EFS and hematologic improvement in
treatment-naïve older CLL/SLL patients, with an 84% reduction in
risk of death, and an acceptable safety profile.
Disclosures: Off Label Use: ibrutinib in first-line CLL (including non-del17p CLL). Barr: Gilead: Consultancy ;Abbvie: Consultancy ; Pharmacyclics LLC, an AbbVie Company: Consultancy , Research Funding . Robak: Janssen:Consultancy , Research Funding ; MorphoSys AG: Consultancy , Honoraria , Research Funding ; Gilead Sciences:Research Funding . Owen: Janssen: Honoraria ; Lundbeck: Honoraria ; Gilead: Honoraria ; Roche: Honoraria . Ghia:Adaptive: Consultancy ; Pharmacyclics: Consultancy ; Gilead: Consultancy , Research Funding , Speakers Bureau ;GSK: Research Funding ; AbbVie: Consultancy ; Janssen: Consultancy ; Roche: Consultancy , Research Funding ;Acerta Pharma BV: Research Funding . Hillmen: Janssen: Consultancy , Honoraria , Research Funding ; AbbVie:Honoraria , Research Funding ; Roche Pharmaceuticals: Honoraria , Research Funding ; Novartis: Honoraria , Research Funding ; Celgene: Research Funding ; Pharmacyclics LLC, an AbbVie Company: Honoraria , Research Funding ; Gilead: Honoraria , Research Funding . Bartlett: Novartis: Research Funding ; Millennium: Research Funding ; Pharmacyclics: Research Funding ; Gilead: Consultancy , Research Funding ; Genentech: Research Funding ; MERC: Research Funding ; Insight: Research Funding ; Colgene: Research Funding ; Medimmune:Research Funding ; Seattle Genetics: Consultancy , Research Funding ; Janssen: Research Funding ; Pfizer:Research Funding ; Kite: Research Funding ; Dynavax: Research Funding ; Idera: Research Funding ; Portola:Research Funding ; Bristol Meyers Squibb: Research Funding ; Infinity: Research Funding ; LAM Theapeutics:Research Funding . Coutre: Gilead: Research Funding ; AbbVie: Research Funding ; Pharmacyclics LLC, an AbbVie Company: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees , Research Funding ;Novartis: Research Funding ; Celgene Business Advisory Board: Membership on an entity’s Board of Directors or advisory committees ; Janssen: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees . Quach: Celgene Corp, ONYX, Janssen, Takeda, Novartis, BMS: Honoraria , Research Funding .Janssens: Mundipharma: Speakers Bureau ; Roche: Consultancy , Speakers Bureau ; Janssen: Consultancy .O'Dwyer: Celgene: Honoraria , Research Funding . Hellmann: BMS: Consultancy , Other: funding of travel, accomodations or expenses , Speakers Bureau ; Novartis: Consultancy , Other: funding of travel, accomodations or expenses , Research Funding , Speakers Bureau . Schuh: Acerta Pharma BV: Research Funding . Siddiqi: Seattle Genetics: Speakers Bureau ; Pharmacyclics/Jannsen: Speakers Bureau ; Kite pharma: Other: attended advisory board meeting . Tam: AbbVie: Honoraria ; Roche: Honoraria ; Janssen: Consultancy , Honoraria , Research Funding . Keating: Glaxo-Smith-Kline Inc.: Other: Advisory board ; Celgene Corp.: Consultancy . Suri: Pharmacyclics LLC, an AbbVie Company: Employment . Zhou: Pharmacyclics LLC, an AbbVie Company: Employment . Clow:Pharmacyclics LLC, an AbbVie Company: Employment . Styles: Pharmacyclics LLC, an AbbVie Company:Employment . James: Pharmacyclics LLC, an AbbVie Company: Employment . Kipps: Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor ; Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor . Burger: Pharmacyclics LLC, an AbbVie Company: Research Funding .
Datum přednesení příspěvku: 7. 12. 2015