1. Phase II PCYC-1121 Trial: Ibrutinib Monotherapy Active in R/R Marginal Zone Lymphoma
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*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.
R/R, relapsed/refractory.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. Ibrutinib in R/R MZL (PCYC-1121): Background
Marginal zone lymphoma: indolent B-cell lymphoma; ~ 10% of NHL cases
Treatment
No standard of care, with no specifically approved treatment
Options include chemoimmunotherapy and anti-CD20 antibodies
Linked to infection-induced B-cell growth and survival[1]
Ibrutinib: first-in-class oral inhibitor of BTK
Approved to treat CLL/SLL, mantle cell lymphoma, and Waldenström’s macroglobulinemia
BTK: major component of B-cell receptor signaling[1]
Multicenter, open-label phase II trial studied efficacy and safety of ibrutinib in pts with R/R MZL[2]
CLL, chronic lymphocytic leukemia; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; R/R, relapsed/refractory; SLL, small lymphocytic leukemia.
Slide credit: clinicaloptions.com
1. Niemann et al. Semin Cancer Biol. 2013;23: Noy A, et al. ASH Abstract 1213.

3. Ibrutinib in R/R MZL (PCYC-1121): Study Design
Pts with R/R MZL with
≥ 1 prior therapy including ≥ 1 anti-CD20-directed regimen, ECOG PS 0-2
(N = 63)
Until disease progression or unacceptable toxicity
Ibrutinib
560 mg PO once daily
Primary endpoint: ORR by IRC using 2007 IWG criteria
Secondary endpoints: DoR, PFS, OS, and safety
DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; IRC, independent review committee; IWG, International Working Group; MZL, marginal zone lymphoma; PS, performance status; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

4. Ibrutinib in R/R MZL (PCYC-1121): Baseline Characteristics
Total (N = 63)
Median age, yrs (range)
66 (30-92)
Age ≥ 65 yrs, n (%)
36 (57)
MZL subtype, n (%)
Splenic
Nodal
Extranodal
14 (22)
17 (27)
32 (51)
Bulky disease > 6 cm, n (%)
Bone marrow involvement, n (%)
21 (33)
Baseline cytopenias, n (%)
Any cytopenia
Hemoglobin ≤ 11 g/dL3
Platelet count ≤ 100,000 per mm3
Absolute neutrophil count ≤ 1500 per mm3
27 (43)
6 (10)
1 (2)
LDH, ≥ 350 U/L, n (%)
12 (19)
Creatinine clearance < 60 mL/min, n (%)
9 (14)
Characteristic
Total (N = 63)
Prior therapies, median n (range)
2 (1-9)
No. prior systemic therapies, n (%) 1 2
≥ 3
23 (37)
18 (29)
22 (35)
Type of prior therapy, n (%)
Rituximab monotherapy
Rituximab chemoimmunotherapy
Radiation
Splenectomy
ASCT
17 (27)
40 (63)
9 (14)
4 (6)
2 (3)
Refractory to most recent therapy, n (%)
14 (22)
B symptoms at baseline, n (%)
15 (24)
ASCT, autologous stem cell transplantation; LDH, lactate dehydrogenase; MZL, marginal zone lymphoma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

5. Ibrutinib in R/R MZL (PCYC-1121): Response
ORR per IRC assessment: 48%
ORR concordance rate (IRC and investigator assessment): 85%
Clinical benefit rate (CR + PR + SD) per IRC assessment: 83%
Tumor shrinkage in 79% of pts including all 3 MZL subtypes
DoR at 18 mos: 62%
Median time to response
Initial: 4.5 mos
Best: 5.2 mos
DoR, duration of response; IRC, independent review committee; MZL, marginal zone lymphoma; R/R, relapsed/refractory; SD, stable disease.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

6. Ibrutinib in R/R MZL (PCYC-1121): Response Across Pt Subgroups
ORR, % (95% CI)
Extranodal disease
Yes No 36 24
50 (35-66)
46 (28-65)
Bone marrow involvement 21 35
62 (41-79)
46 (31-62)
Prior regimens 1 2
≥ 3 22 18 20
50 (31-69)
44 (25-66)
50 (30-70)
Prior chemoimmunotherapy 39
46 (32-61)
52 (32-72)
Prior rituximab only 16
69 (44-86)
Subgroup n
ORR, % (95% CI)
All pts 60
48 (35-62)
MZL subtype
Extranodal
Splenic
Nodal 30 13 17
50 (33-67)
54 (29-77)
41 (22-64)
Age
< 65 yrs
≥ 65 yrs 24 36
58 (39-76)
42 (27-58)
Baseline ECOG PS
≥ 1 32 28
44 (28-61)
54 (36-71)
Tumor size (nodal/extranodal)
> 6 cm
≤ 6 cm 14 43
50 (27-73)
46 (32-61)
Tumor size (nodal) 9 41
56 (27-81)
ECOG, Eastern Cooperative Oncology Group; MZL, marginal zone lymphoma; PS, performance status; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

7. Ibrutinib in R/R MZL (PCYC-1121): AEs
Median duration of therapy: 11.6 mos
Median follow-up: 19.4 mos
38% of pts still on study treatment
Reasons for discontinuation: disease progression (32%), AEs (17.5%), withdrawal of consent (6%), investigator decision (6%)
AEs
Most common AEs: fatigue, diarrhea, anemia, nausea, thrombocytopenia, peripheral edema, cough, arthralgia, dyspnea, upper respiratory infection
Leading to dose reductions: 6 pts (10%)
Treatment discontinuation: 11 pts (17.5%)
Treatment-emergent deaths: 1 pt each PD, cerebral hemorrhage, parainfluenza pneumonia
AE, adverse event; MZL, marginal zone lymphoma; PD, progressive disease; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

8. Ibrutinib in R/R MZL (PCYC-1121): Conclusions
Ibrutinib monotherapy is active in R/R MZL
ORR in total population: 48%
Effective across nodal, extranodal, and splenic subgroups
AE profile consistent with previous experience
Investigators conclude ibrutinib is an effective chemotherapy-free therapeutic option for R/R MZL
AE, adverse event; MZL, marginal zone lymphoma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Noy A, et al. ASH Abstract 1213.

9. Go Online for More CCO Coverage of ASH 2016!
Short slideset summaries of all the key data
Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Leukemias
Lymphomas/CLL
Myeloma/plasma cell disorders
MDS and myeloproliferative neoplasms
clinicaloptions.com/oncology