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.

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;321:974-977. 2. Raponi S, et al. Leuk Lymphoma. 2011;52:1098-1107. 3. Piccaluga PP, et al. Leuk Lymphoma. 2011;52:325-327. 4. Topp MS, et al. Lancet Oncol. 2015;16:57-66. 5. Stein AS, et al. ASH 2015. Abstract 861. Slide credit: clinicaloptions.com

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 2015. Abstract 861. 2. Topp MS, et al. Lancet Oncol. 2015;16:57-66. Slide credit: clinicaloptions.com

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 2015. Abstract 861.

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 2015. Abstract 861.

Blinatumomab in R/R ALL: RFS and OS Median RFS (n = 29): 7.4 mos (95% CI: 5.0-10.1) Median OS (N = 64): 8.5 mos (95% CI: 4.2-11.2) ALL, acute lymphoblastic leukemia; RFS, relapse-free survival; R/R, relapsed/refractory. Slide credit: clinicaloptions.com Stein AS, et al. ASH 2015. Abstract 861.

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 2015. Abstract 861. 2. Topps MS, et al. Lancet Oncol. 2015;16:57-66. Slide credit: clinicaloptions.com

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 2015. Abstract 861.

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 2015. Abstract 518. Topp MS, et al. Lancet Oncol. 2015;16:57-66. Slide credit: clinicaloptions.com

Go Online for More CCO Coverage of ASH 2015! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Acute leukemias/chronic leukemias Myeloma/plasma cell disorders Lymphomas MDS and myeloproliferative neoplasms clinicaloptions.com/oncology