1. Phase II Study: Pembrolizumab Plus Pomalidomide and Dexamethasone Active in R/R Multiple Myeloma
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. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Background
PD-1/PD-L1 pathway blockade being exploited in several cancers to restore cytotoxic T-cell activity and anticancer immunity[1]
Pembrolizumab: humanized anti–PD-1 monoclonal antibody
Pomalidomide: immunomodulatory thalidomide analogue indicated in combination with dexamethasone for pts with MM and ≥ 2 previous treatments including lenalidomide and a PI with progression ≤ 60 days of last regimen
Current study evaluates the safety and efficacy of pembrolizumab combined with pomalidomide and dexamethasone in pts with relapsed/refractory MM[2]
MM, multiple myeloma; PI, proteasome inhibitor; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
1. Boussiotis VA. N Engl J Med. 2016;375: Badros AZ, et al. ASH Abstract 490.

3. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Study Design
Exploratory trial
Primary endpoint: safety
Secondary endpoints: ORR, PFS, OS
Exploratory endpoints: correlation of BL levels of PD-1 and PD-L1 in BM with response
Mo 24
Pts with R/R MM and 2 lines of previous tx including IMid and PI; ECOG PS < 2 and adequate organ function;
no active autoimmune disease requiring treatment or history of severe autoimmune disease
(N = 48)
Pembrolizumab* 200 mg IV Days 1, 14 +
Pomalidomide 4 mg PO Days
Dexamethasone 40 mg† PO Days 1, 7, 14, 21
Q28D
Pembrolizumab 200 mg IV/mo +
Pomalidomide 4 mg PO +
Dexamethasone 40 mg† PO
Responders
*First 6 pts received pembrolizumab on Day 1 only.
†Pts > 70 yrs of age received 20 mg.
BL, baseline; BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; IMiD, immunomodulatory drug; MM, multiple myeloma; PI, proteasome inhibitor; PS, performance status; R/R, relapsed/refractory; tx, treatment.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

4. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Baseline Characteristics
Pts
(N = 48)
Median age, yrs (range)
< 65 yrs, %
65-74 yrs, %
≥ 75 yrs, %
64 (35-83) 54 37 13
Male sex, % 66
Race, %
White
Black
Other 38 8
ECOG PS 0-1, % 92
Isotype, %
IgG isotype
IgA isotype
IgD isotype
Light chain in urine
Light chain in serum only 60 15 2
Characteristic
Pts
(N = 48)
Median LDH IU/L (range)
> ULN, %
509 ( ) 8
Median creatinine, mg/dL (range)
1 ( )
Median BM plasmacytosis, % (range)
20 (15-100)
Standard-risk cytogenetics, %
Normal
Hyperdiploid
t(11;14) 38 21 13 4
High-risk cytogenetics, %
del(17p)
t(14;16)
t(14;20)
t(4;14)
1q+ 62 10 27
BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; MM, multiple myeloma; PI, proteasome inhibitor; PS, performance status; R/R, relapsed/refractory; ULN, upper limit of normal.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

5. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Prior Therapy
Characteristic
Pts (N = 48)
Median time from diagnosis to study, yrs (range)
4 (1.2-26)
Median lines of earlier therapy (range)
2 lines, %
3 lines, %
> 3 lines, %
3 (2-5) 35 38 27
Previous therapy, %
ASCT
Bortezomib
Carfilzomib
Lenalidomide
Thalidomide 72
100 50 98 2
Refractory, %
Proteasome inhibitors
IMiDs + proteasome inhibitors 79 90 73
ASCT, autologous stem cell transplantation; IMiD, immunomodulatory drug; MM, multiple myeloma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

6. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Adverse Events
All Grades
Grade > 3
In > 30% of pts
Fatigue
Neutropenia
Hyperglycemia
Thrombocytopenia
Anemia
Dizziness
Constipation
URT infection
Dyspnea
Edema
In > 20% to 30% of pts
Lymphopenia
Muscle spams
Rash
Diarrhea
Infection
Pneumonia
Nausea
In ≥ 10% to 20% of pts
Hypotension
Peripheral neuropathy
Arrhythmia
irAEs in any pt
Pneumonitis (12%)*
Hypothyroidism (10%)
Adrenal
Hepatitis
Vitiligo
Hypothyroidism
Pneumonitis
irAE, immune-related adverse event; MM, multiple myeloma; R/R, relapsed/refractory; URT, upper respiratory tract.
*With ground glass opacification in 6 pts who presented with cough, shortness of breath, low-grade fever.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

7. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Safety
Outcome
Pts (N = 48)
Median no. of cycles (range)
Median follow-up, mos
8 (3-23)
9.6
Dose reduction, n (%)
Pembrolizumab, n*
Pomalidomide, n†
Dexamethasone, n‡
22 (49) 2 13 7
Discontinuation due to regimen toxicity, n (%)
Pneumonitis, n
Shortness of breath, n
Fatigue, n
5 (11) 3 1
Deaths, n 9
Disease progression, n 23
MM, multiple myeloma; R/R, relapsed/refractory.
*Pneumonitis, n = 2
†Fatigue, n = 5; neutropenia, n = 3; rash, n = 2; palpitation, n = 1; muscle spasm, n = 1; peripheral neuropathy, n = 1.
‡Uncontrolled hyperglycemia, n = 3; weight gain, n = 2; cellulitis, n = 1; lack of sleep, n = 1.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

8. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Efficacy
Response, %
Full Efficacy Population
(N = 45)
Refractory to 2 Classes
(n = 32)
High-Risk Cytogenetics
(n = 27)
ORR 65 68 56
Clinical benefit 72 69 60
Best response
sCR CR
VGPR PR MR SD PD 7 2 20 36 23 5 3 18 44 22 4 41 31
sCR + CR+ VGPR, % 29 24 15
MM, multiple myeloma; MR, minimal response; PD, progressive disease; R/R, relapsed/refractory, sCR, stringent; SD, stable disease; VGPR, very good PR.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

9. Full Efficacy Population
Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Duration of Response and Survival
Outcome, Mos (95% CI)
Full Efficacy Population
(N = 45)
Median duration of response
16.3 ( )
Median PFS
17.4 ( )
Median OS
Not reached (18.8-not reached)
PFS significantly longer in low-risk vs high-risk subgroups (P = .0366)
MM, multiple myeloma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

10. PD-L1 Marker Expression T-Cell Infiltrate Marker Expression
Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Biomarker Expression and Efficacy
PD-L1 Marker Expression
Response
Negative
(n = 10)
Weakly Positive
(n = 6)
Positive
(n = 27)
ORR, %
sCR CR
VGPR PR
MR + SD + PD 60 20 40 50 77 8 38 23
sCR + CR+ VGPR, %
54*
Median PFS, mos (95% CI)
17.4
( )
17.5
( )
NR (3.7-NR)†
T-Cell Infiltrate Marker Expression
Response, %
CD3+/
PD1+
(n = 6)
PD1-
(n = 10)
CD3-/
(n = 22)
Best response
sCR CR
VGPR PR
MR + SD + PD 33 67 70 10 40 20 30 73 14 9 50 23
sCR + CR+ VGPR, %
23%‡
Median PFS, mos
(95% CI)
6.3
(2.6-NR)
16.5
( )
17.5¶
(11.7-NR)
MM, multiple myeloma; MR, minimal response; NR, not reached; PD, progressive disease; R/R, relapsed/refractory; sCR, stringent CR; SD, stable disease; VGPR, very good PR.
*P = .05 vs PD-L1 negative. †P = .5 vs PD-L1 negative.
‡P = .12 vs CD3+/PD-1+. ¶P = .05 vs CD3+/PD-1+.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

11. Pembrolizumab, Pomalidomide, Dexamethasone for R/R MM: Investigator Conclusions
In this small study of pts with R/R MM, the combination of pembrolizumab/pomalidomide/dexamethasone appears active
AEs occurred in ~ 50% of the study population
Discontinuation in 10%; most AEs manageable
These results suggest that future studies are warranted to further understand the role of PD-1/PD-L1 inhibitors in pts with MM
AE, adverse events; MM, multiple myeloma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Badros AZ, et al. ASH Abstract 490.

12. 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