Program: Oral and Poster Abstracts
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Poster II
Methods: Data were analyzed for pts with R/R FL (N=16) treated with oral ibrutinib in the phase I study (PCYC-04753), where pts received escalating doses of ibrutinib 1.25-12.5 mg/kg/day per cycle (1 cycle = 28 days + 7 days rest) or continuous doses of ibrutinib 8.3 mg/kg/day or 560 mg/day fixed dose (1 cycle = 35 days). Pts with stable disease or better, who received therapy for 6 months, continued ibrutinib at a fixed dose of 560 mg/day in the extension study (PCYC-1103) until progression or unacceptable toxicity. Pt data categories included low-dose (1.25 mg/kg/day, 2.5 mg/kg/day, or 5 mg/kg/day) or high-dose (8.3 mg/kg/day or 12.5 mg/kg/day) groups.
Results: Eight pts each were categorized into low-dose and high-dose groups. Baseline characteristics were similar, but median treatment duration was longer for the high-dose group (Table; 12 vs. 4 months). Increased ORR (63% vs. 25%) and CR rates (38% vs. 0%) were observed in the high-dose compared with low-dose group (Table). Median duration of response (DOR) was longer in the high-dose group (12 vs. 3 months), as was median progression-free survival (PFS; 24 vs. 9 months). Median overall survival (OS) was not reached (NR) in either group. Grade ≥3 adverse events (AEs) occurred in 3 pts in each group. Common grade ≥3 AEs reported in ≥3 pts in the combined groups included (low-dose, high-dose) diarrhea (n=2, 6), fatigue (n=3, 4), nausea (n=2, 4), cough (n=3, 2), myalgia (n=1, 3), headache (n=0, 3), muscle spasms (n=1, 2), pruritus (n=0, 3), and rash (n=0, 3). Serious AEs occurred in 3 pts in the low-dose and 1 pt in the high-dose group. AEs leading to treatment discontinuation occurred in 2 pts in each group. No fatal AEs occurred. Among 4 pts (high-dose group) receiving ibrutinib beyond 1 year (range, 18 to 61 months), no unexpected or increased AEs were observed; 1 pt experienced 2 grade 3 AEs (non-cardiac chest pain and vomiting), both within 60 days from start of treatment and lasting 1 day. No other grade ≥3 AEs occurred among these 4 pts.
Conclusions: Higher doses of single-agent ibrutinib were associated with increased response rates and prolonged PFS in pts with R/R FL. A higher dose was not associated with increased AEs or with cumulative toxicity during extended therapy. In the current analysis, pts with FL derived the most benefit from ibrutinib doses at 8.3 mg/kg/day or higher. A study testing single-agent ibrutinib at 560 mg/day in pts with R/R FL is ongoing (Bartlett Blood 2014) as is a phase 2 study evaluating ibrutinib 560 mg/day in chemoimmunotherapy refractory FL.
Table. Patient Characteristics and Efficacy |
||
|
Low dose |
High dose |
Median age, yrs (range) |
57 (48-70) |
62.5 (41-71) |
Median no. of prior therapies (range) |
3 (1-4) |
2 (1-5) |
Ann Arbor stage III/IV disease, n (%) |
6 (75) |
6 (75) |
FLIPI score, % (low / intermediate / high)* |
25 / 38 / 38 |
13 / 38 / 50 |
Median treatment duration, months (range) |
3.8 (0.5-11.1) |
12.4 (0.2-61.5) |
ORR, n (%) |
2 (25) |
5 (63) |
Median DOR, months (range) |
n=2; 3.4 (1.8-4.9) |
n=5; 12.3 (4.8-51.3) |
Median PFS, months (95% CI) |
9.2 (0.5, 13.4) |
23.7 (2.2, NE) |
10-month PFS, % |
35.7 |
70 |
Median OS, months (95% CI) |
NR |
NR |
10-month OS, % |
100 |
100 |
*FLIPI scores from baseline data. NE, not estimable |
Disclosures: Off Label Use: single-agent ibrutinib therapy in patients with relapsed FL. Boyd: Celgene: Research Funding , Speakers Bureau ; Genentech: Research Funding ; US Oncology: Research Funding ; GSK: Research Funding . Sharman: Gilead: Consultancy , Honoraria , Research Funding , Speakers Bureau ; TG Therapeutics, Inc.: Research Funding ; Janssen: Research Funding ; Roche: Research Funding ; Celgene Corporation: Consultancy , Research Funding ; Pharmacyclics: Consultancy , Honoraria , Research Funding ; Calistoga: Honoraria . Smith: Pharmacyclics: Consultancy ; Celgene: Consultancy . Clow: Pharmacyclics LLC, an AbbVie Company: Employment . Chu: Pharmacyclics LLC, an AbbVie Company: Employment .
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*signifies non-member of ASH