1. Phase II KEYNOTE-170/KEYNOTE-013 Update: Pembrolizumab in Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma
Integrating New Malignant Hematology Findings Into Practice: Independent Conference Coverage of ASH 2018* December 1-4, 2018; 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.
Supported by educational grants from AbbVie, AstraZeneca, Celgene Corporation, Dova Pharmaceuticals, Incyte, Jazz Pharmaceuticals, Novartis Pharmaceuticals, Pharmacyclics, Seattle Genetics, and Takeda Oncology.

2. About These Slides
Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients
When using our slides, please retain the source attribution:
These slides may not be published, posted online, or used in commercial presentations without permission. Please contact for details
Slide credit: clinicaloptions.com
Disclaimer: The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Background
R/R PMBCL associated with poor outcomes, few treatment options[1]
Genetic abnormalities (eg, activation of NF-kB, JAK/STAT[2]; amplification/translocation of 9p24[3-6]) often lead to overexpression of PD-L1 and PD-L2 in PMBCL
May be sensitive to PD-1 blockade
Pembrolizumab: humanized IgG4 monoclonal antibody against PD-1
Phase Ib KEYNOTE-013 showed preliminary efficacy, safety of pembrolizumab in PMBCL[1]
41% ORR; 12% CR rate; median DoR not reached
Phase II KEYNOTE-170 extends KEYNOTE-013 and adds biomarker analyses[1]
Current analysis presents updated safety, efficacy data from KEYNOTE-013 and full KEYNOTE-170 cohort with pembrolizumab in patients with R/R PMBCL
DoR, duration of response; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory.
1. Armand. ASH Abstr Savage. Blood. 2003;12: Green. Blood. 2010;17: Twa. Blood. 2014;123: Shi. Am J Surg Path. 2014;38: Chen. Clin Can Res. 2013;13:3462.
Slide credit: clinicaloptions.com

4. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Study Design
Phase Ib KEYNOTE-013
R/R PMBCL patients ≥ 18 yrs of age without ASCT*
(N = 21)
Pembrolizumab
10 mg/kg Q2W (patients 1-10)
or 200 mg Q3W (patients 11-21)
Treatment up to 2 yrs or until unacceptable toxicity, PD, or study withdrawal
Response assessment by PET/CT scan:
KEYNOTE-013: Wk 12 then Q8W (10 mg/kg Q2W) or Wks 6, 12 then Q9W (200 mg Q3W), IWG 2007 criteria
KEYNOTE-170: Wk 12 then Q12W, IWG 2007 criteria
Phase II KEYNOTE-170
R/R PMBCL patients ≥ 18 yrs of age without ASCT,* failed ≥ 2 prior regimens
(N = 53)
Pembrolizumab
200 mg Q3W
Treatment up to 2 yrs or until unacceptable toxicity, PD, or study withdrawal
ASCT, autologous stem cell transplantation; DoR, duration of response; IWG, International Working Group; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory.
Primary endpoints: ORR, safety (KEYNOTE-013 only) Secondary endpoints: DoR, PFS, OS, safety (KEYNOTE-170)
*Failed, ineligible, or refused.
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228. NCT

5. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Patient Characteristics
KEYNOTE-013 (N = 21)
KEYNOTE-170 (N = 53)
Median age, yrs (range)
31 (22-62)
33 (20-61)
Female, n %
14 (67)
30 (57)
Prior transplant, n (%)
8 (38)
14 (26)
Median prior therapies, n (range)
3 (2-9)
3 (2-8)
Prior radiation, n (%)
15 (71)
17 (32)
Prior rituximab, n (%)
21 (100)
53 (100)
PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228.

6. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Efficacy
Characteristic, n (%)
KEYNOTE-013
(N = 21)
KEYNOTE-170†
(N = 53)
KEYNOTE-170‡ OR CR PR
10 (48)
7 (33)
3 (14)
24 (45)
7 (13)
17 (32)
23 (43)
11 (21)
12 (22) SD
5 (24)
5 (9) PD
4 (19)
12 (23)
13 (25)
Nonevaluable/ no assessment*
2 (10)
Characteristic
KEYNOTE-013
(N = 21)
KEYNOTE-170
(N = 53)
Median duration of follow-up, mos
29.1
12.5
Median time to response, mos
2.7§
2.8ǁ
PFS
12-mo, %
Median, mos (range) 47
10.4 (3.4-NR) 38
5.5 ( ) OS 65
31.4 (4.9-NR) 58
NR (7.3-NR)
NR, not reached; PD, progressive disease; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory; SD, stable disease.
*Insufficient data for response assessment. †Cheson criteria. ‡Lugano criteria.
§2 patients converted from PR to CR after 12 mos; 4 patients maintained CR after 2 yrs on treatment (2.3+, 2.5+, 3+, 3.5+ yrs). ǁNo relapses in patients with CR reported at database lock.
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228.

7. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Safety
TRAEs, n (%)
KEYNOTE-013 (N = 21)
KEYNOTE-170 (N = 53)
Any TRAEs
15 (71)
30 (57)
Grade 3/4 TRAEs
Neutropenia
Febrile neutropenia
Fatigue
Increased ALT
Increased AST
Hyponatremia
C difficile infection
Pneumonia
Tumor flare
VTE
5 (24)
3 (14)
1 (5)*
1 (5)
12 (23)
7 (13)
1 (2)
1 (2)*
AEs, n (%)
KEYNOTE-013 (N = 21)
KEYNOTE-170 (N = 53)
Immune-mediated AEs§
Grade 3/4
4 (19)
1 (5)†
6 (11)
1 (2)‡
*Discontinuation. †Myositis. ‡Pneumonitis.
§Includes thyroid disease, colitis, myositis, pneumonitis.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory; TRAE, treatment-related adverse event; VTE, venous thrombotic event
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228.

8. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Biomarker Analyses
Patients with tissue available for biomarker analysis (n = 42)
KEYNOTE-013 (n = 5), KEYNOTE-170 (n = 37)
IHC membranous staining evaluated and scored by 2 independent pathologists
H score by IHC reflects percentage of PD- L1+ cells and relative intensity of staining
Range 0-300: 0 = no/low PD-L1+; = ~ 50% cells PD-L1+
PD-L1 H score correlated with magnitude of 9p24 abnormality by FISH (n = 40; P = )
PD-L1 H score significantly associated with PFS (P = .029)
Median PFS for 0, mos: 2.0 ( )
Median PFS for 1-99, mos: 6.3 ( )
Preselected Cutoffs
H Score
1-99
≥ 100
PD-L1 (n = 42), n (%)
8 (20)
19 (46)
14 (34)
PD-L2 (n = 41), n (%)
22 (54)
4 (10)
15 (37)
PD-L1/L2*
Patients, n (%)
ORR, %
PFS, mos‡
5 (12) 0†
1.2
12 (29) 33
4.8
24 (59) 63
11.1
PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory.
*Both H scores = 0, at least 1 H score ≥ 100, all others †P = ‡P < .001.
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228.

9. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Conclusions
Pembrolizumab results in durable responses in R/R PMBCL
Median DoR not yet reached with median follow-up of 29.1 mos (KEYNOTE-013), 12.5 mos (KEYNOTE-170)
12-mo OS > 50%; durable CR in both studies
Manageable toxicity profile
Biomarker analyses: PD-L1 H score associated with PFS; patients lacking expression of PD-L1/L2 have reduced response to pembrolizumab, worse outcomes
Data support receptor-level blockade in R/R PMBCL, per investigators
Future studies needed to validate/refine
Pembrolizumab received accelerated FDA approval for R/R PMBCL in June 2018
DoR, duration of response; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Armand. ASH Abstr 228.

10. Go Online for More CCO Coverage of ASH 2018!
Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in:
Leukemias
Lymphomas/CLL
Multiple Myeloma
Other Hematologic Diseases
clinicaloptions.com/oncology