1. Blinatumomab After AlloHSCT in Patients With R/R B-Precursor ALL
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.
AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; R/R, relapsed/refractory.
This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, Seattle Genetics, and Takeda Oncology.

2. Blinatumomab in R/R ALL: Background
Poor outcomes for pts with R/R ALL treated with alloHSCT
Blinatumomab: bispecific T cell–engaging antibody
Targets T cells to CD19+ B cells (normal and malignant)[1]
CD19 expressed on all tested B-lineage ALL cells[2,3]
Phase II study of blinatumomab as monotherapy for R/R B-precursor ALL resulted in 43% of pts achieving CR or CRh after 2 cycles[4]
82% of CR/CRh pts achieved MRD negativity[4]
Current exploratory analysis evaluated RFS, OS, and AEs in subset of Ph- ALL pts who relapsed after alloHSCT prior to blinatumomab treatment[5]
AE, adverse event; AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; CRh, complete response with partial hematologic recovery; MRD, minimal residual disease; Ph, Philadelphia chromosome; RFS, relapse-free survival; R/R, relapsed/refractory.
1. Bargou R, et al. Science. 2008;321:
2. Raponi S, et al. Leuk Lymphoma. 2011;52:
3. Piccaluga PP, et al. Leuk Lymphoma. 2011;52:
4. Topp MS, et al. Lancet Oncol. 2015;16:57-66.
5. Stein AS, et al. ASH Abstract 861.
Slide credit: clinicaloptions.com

3. Blinatumomab in R/R ALL: Study Design
Subanalysis[1] of single-arm phase II study[2]
Primary endpoint: CR/CRh during first 2 cycles
Secondary endpoints: CR, CRh, OS, RFS, safety, alloHSCT rate; exploratory: MRD by PCR during first 2 cycles
Primary Endpoint Assessment
During First 2 Cycles
Adult pts with
Ph- B-precursor R/R ALL;
≥ 10% BM blasts
± extramedullary disease;
ECOG PS 0-2;
relapse w/in 12 mos alloHSCT but no alloHSCT ≤ 3 mos,
no GvHD G2-4,
no GvHD tx ≤ 2 wks,
or CNS pathologies
(N = 64)
Blinatumomab cIV
9 µg/day x Days 1-7 (cycle 1)
28 µg/day x ≤ 2 cycles
(4 wks on, 2 wks off)
Consolidation:
Blinatumomab cIV
28 µg/day x ≤ 3 cycles
(4 wks on, 2 wks off)
Follow-up
≤ 24 mos
AlloHSCT offered to pts in CR/CRh* in any cycle
AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; ANC, absolute neutrophil count; BM, bone marrow; cIV, continuous intravenous infusion; CNS, central nervous system; CRh, complete response with partial hematologic recovery; ECOG, Eastern Cooperative Oncology Group; GvHD, graft vs host disease; MRD, minimal residual disease; Ph, Philadelphia chromosome; PS, performance status; RFS, relapse-free survival; R/R, relapsed/refractory; tx, treatment.
*CRh: Platelets > 50,000/µL; ANC > 500/µL.
1. Stein AS, et al. ASH Abstract Topp MS, et al. Lancet Oncol. 2015;16:57-66.
Slide credit: clinicaloptions.com

4. Blinatumomab in R/R ALL: Baseline Characteristics
Pts
(N = 64)
Age, median yrs (range)
32 (19-74)
Age group, %
18 to younger than 35 yrs
35 yrs or older 63 37
Male, % 67
Time to relapse,* median mos (range)
6 (1-33)
Number of prior salvage therapies, % of pts 1 2
≥ 3 14 36 19 31
Previous post alloHSCT salvage therapy, % 69
ALL, acute lymphoblastic leukemia; AlloHSCT, allogeneic hematopoietic stem cell transplantation; R/R, relapsed/refractory.
*Relapse from last previous alloHSCT or post alloHSCT salvage therapy.
Slide credit: clinicaloptions.com
Stein AS, et al. ASH Abstract 861.

5. Blinatumomab in R/R ALL: Efficacy
Parameter, %
Pts
(N = 64)
95% CI
Hematologic response
CR/CRh, first 2 cycles
CR, first 2 cycles
CRh, first 2 cycles
CR/CRh, first cycle*
Blast-free hypoplastic or aplastic BM
Failure to respond
Insufficient treatment duration 45 28 17 76 6 19 11
33-58
18-41
9-29 --
2-15
10-31
Treatment outcomes
AlloHSCT after CR or CRh*
100-day transplant-related mortality 24 14
2-67
Molecular response†
MRD response
Complete MRD response
MRD nonresponse
No MRD assessment
(n = 18) 89 83
AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; BM, bone marrow; CRh, complete response with partial hematologic recovery; MRD, minimal residual disease; R/R, relapsed/refractory.
*n = 29. †Pts who achieved CR in first 2 cycles.
Slide credit: clinicaloptions.com
Stein AS, et al. ASH Abstract 861.

6. Blinatumomab in R/R ALL: RFS and OS
Median RFS (n = 29): 7.4 mos (95% CI: )
Median OS (N = 64): 8.5 mos (95% CI: )
ALL, acute lymphoblastic leukemia; RFS, relapse-free survival; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Stein AS, et al. ASH Abstract 861.

7. Blinatumomab in R/R ALL: AEs
Grade ≥ 3 AEs in ≥ 5 pts, %
Prior AlloHSCT[1]
(N = 64)
ITT Population[2]
(N = 189)
Neutropenia
Febrile neutropenia 22 20 16 26
Anemia 17 14
Thrombocytopenia 9
Increased ALT 13 7
Pyrexia 11
Hypokalemia
Leukopenia 8
Pneumonia
Increased AST 4
Increased bilirubin
Encephalopathy 3
Hypotension
Decreased WBC count 5
AE, adverse event; AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRh, complete response with partial hematologic recovery; GI, gastrointestinal; ITT, intent to treat; PD, progressive disease; R/R, relapsed/refractory; WBC, white blood cell.
Death in 8 pts, none of whom achieved CR/CRh: infection (n = 5), 1 each GI hemorrhage, PD, respiratory failure
1. Stein AS, et al. ASH Abstract Topps MS, et al. Lancet Oncol. 2015;16:57-66.
Slide credit: clinicaloptions.com

8. Blinatumomab in R/R ALL: GvHD
GvHD in 7 pts during treatment until 30 days following treatment
Pts With GvHD, n
Pts With Prior AlloHSCT (N = 64)
Grade 1
Grade 2
Grade 3
Skin 1 2
Nonspecified
Mouth
Multiple events*
Arthralgia
Serum ALP increase
Serum bilirubin increase --
AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; ALP, alkaline phosphatase; GvHD, graft vs host disease; R/R, relapsed/refractory.
*1 pt had 3 different events.
Slide credit: clinicaloptions.com
Stein AS, et al. ASH Abstract 861.

9. Blinatumomab in R/R ALL: Conclusions
Blinatumomab achieved antileukemic activity in Ph- R/R ALL pts after alloHSCT[1]
CR/CRh rate: 45%
Median RFS (7.4 mos) and OS (8.5 mos) were consistent with those reported for ITT population[2]
Blinatumomab does not appear to be associated with increased GvHD
Investigators suggest future investigations combining blinatumomab with other immunotherapies in this pt population
AlloHSCT, allogeneic hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; CRh, complete response with partial hematologic recovery; GvHD, graft vs host disease; ITT, intent to treat; Ph, Philadelphia chromosome; RFS, relapse-free survival; R/R, relapsed/refractory.
Chen R, et al. ASH Abstract Topp MS, et al. Lancet Oncol. 2015;16:57-66.
Slide credit: clinicaloptions.com

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