1. Ibrutinib Plus Rituximab in Treatment-Naive Patients With Follicular Lymphoma
New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, Seattle Genetics, and Takeda Oncology.

2. Frontline Ibrutinib Plus Rituximab in FL: Background
Rituximab commonly used as frontline treatment in FL
Ibrutinib
Oral, irreversible BTK inhibitor affecting B-cell adhesion, migration, survival[1]
Well tolerated with demonstrated therapeutic potential in R/R FL pts[2,3]
Current study evaluates chemotherapy-free combination ibrutinib plus rituximab as frontline therapy[4]
FL, follicular lymphoma; R/R, relapsed/refractory.
1. Wang Y, et al. Clin Pharmacol Ther. 2015;97: Advani, et al. J Clin Oncol. 2013;31: Bartlett, et al. ASH Abstract Fowler NH, et al. ASH Abstract 470.

3. Frontline Ibrutinib Plus Rituximab in FL: Study Design
Multicenter phase II study of combination ibrutinib plus rituximab therapy in previously untreated FL pts
Primary endpoint: ORR
Secondary endpoints: DoR, PFS, OS, and safety
Treatment naive,
stage II, III, or IV FL pts with at least 1 measurable lesion ≥ 2 cm; ECOG PS ≤ 2
(N = 60)
Ibrutinib
560 mg PO QD +
Rituximab
375 mg/m2 IV weekly x 4
Continued until disease progression or toxicity
DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; ORR, overall response rate; OS, overall survival; PS, performance status.
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470.

4. Frontline Ibrutinib Plus Rituximab in FL: Baseline Characteristics
Ibrutinib + Rituximab
(n = 60)
Median age, yrs (range)
65 yrs or older, n (%)
58 (32-84)
18 (30)
Ann Arbor stage III/IV disease, n (%)
48 (80)
FL grade, n (%)
Grade 1
Grade 2
Grade 3a
19 (32)
35 (58)
6 (10)
FLIPI risk scores, n (%)
Low risk (0 - 1)
Intermediate risk (2)
High risk (≥ 3)
7 (12)
23 (38)
30 (50)
ECOG PS, n (%) 1
47 (78)
13 (22)
Bulky disease (≥ 5 cm in at least 1 site), n (%)
≥ 7 cm
≥ 10 cm
12 (20)
2 (3)
ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index; PS, performance status.
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470.

5. Frontline Ibrutinib Plus Rituximab in FL: Response
100 CR PR SD 50
Improvement From Baseline SPD (Max %)
-50 *
N = 60
-100
*Response recorded in database is SD; unresolved query
FL, follicular lymphoma; SD, stable disease; SPD, sum of the products of the greatest perpendicular diameters.
ORR of 82% (49 of 60); CR of 30%
Median follow-up: 13.8 mos with a median time to best response of mos
Median duration of ibrutinib treatment: mos
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470. Reproduced with permission.

6. Frontline Ibrutinib Plus Rituximab in FL: DoR and PFS
100
100 90 90 80 80 70 70 60 60
DoR (%) 50
PFS (%) 50 40 40 30 30 20 20 10 10 3 6 9 12 3 6 9 12 15
Mos From Initiation of Study Treatment
Mos From Initiation of Study Treatment
Pts at Risk, n:
Pts at Risk, n: 49 45 34 9 60 56 53 41 12 1
DoR, duration of response; FL, follicular lymphoma.
At a median follow-up of 13.8 mos:
Median PFS not reached; 12-mo PFS rate of 86%
Median OS not reached; 12-mo OS rate of 98%
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470. Reproduced with permission.

7. Frontline Ibrutinib Plus Rituximab in FL: AEs (≥ 20%)
Fatigue
Diarrhea
Nausea
Constipation
Headache
Grade 1/2 Grade 3/4
Cough
Maculopapular Rash
Vomiting
Dry Eye
Pyrexia
Myalgia
Infusion-Related Reaction
Dizziness
Arthralgia 10 20 30 40 50 60 70 80 90
100
AE, adverse event; FL, follicular lymphoma.
Pts (%)
Grade 3/4 AEs occurred in 29 pts (48%)
 1 pt: fatigue (5%), maculopapular rash (5%), neutropenia (5%), hypertension (3%), and arthritis (3%)
1 death due to Hodgkin’s lymphoma several mos after study discontinuation
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470. Reproduced with permission.

8. Frontline Ibrutinib Plus Rituximab in FL: Additional Safety Outcomes
Characteristic, n (%)
Ibrutinib + Rituximab
(N = 60)
Serious AEs (all in 1 pt each)
Any
Grade 3/4
10 (17)
9 (15)
Bleeding events
19 (32)
Atrial fibrillation
3 (5)
Secondary malignancies
4 (7)
Discontinued ibrutinib due to toxicity/intercurrent illness
Dose reduction of ibrutinib (560 mg to 420 mg) due to toxicity
AE, adverse event; FL, follicular lymphoma.
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470.

9. Frontline Ibrutinib Plus Rituximab in FL: Conclusions
Ibrutinib addition to rituximab in treatment-naive FL pts is highly active with 82% ORR and 30% CR
Combination chemotherapy-free treatment well tolerated with few grade 3/4 serious AEs
AE, adverse event; FL, follicular lymphoma.
Slide credit: clinicaloptions.com
Fowler NH, et al. ASH Abstract 470.

10. Go Online for More CCO Coverage of ASH 2015!
Short slideset summaries of all the key data
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Acute leukemias/chronic leukemias
Myeloma/plasma cell disorders
Lymphomas
MDS and myeloproliferative neoplasms
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