1. A N O V E L A G E N T L E A D I N G B i T E T H E R A P Y
Blinatumomab

2. Acute Lymphoblastic Leukemia (ALL)
 Cancer of stem cells in bone marrow that produce
lymphocytes.
 Hematologic progenitor cells originate in bone marrow.
 Erythrocytes and platelets
 Rapid proliferation of lymphocytes causes other cell
types to be crowded out.
 Abnormal white blood cells accumulate
 Decrease in number and production of other cell types
 Clinical Markers
 Absolute Neutrophil Count <500/µL
 Platelets <50,000/µL
 WBC >100,000 (T-cell ALL) >30,000 (B-cell ALL)
 Hemoglobin <7g/dL

3. Salvage Therapy Relapse or Refractory ALL
 Clofarbine
 Vincristine
 Liposomal Vincristine
 Nelarbine
 Cytarabine
 Liposomal Cytarabine
 Fludarbine
 Idarubicin
 Asparaginase
 MTX
 Etoposide
 Mitoxantrone
 Cyclophosphamide
 Anthracyclines
 Dexamethasone, Prednisone
 Remission rates for newly
diagnosed adult patients
are over 80% with standard
induction regimens.
 Adoptive Cell Transfer (ACT)
 Chimeric antigen receptors
(CAR)
 Pathway to allogenic
hematopoietic stem cell
transplant (HSCT)
 Bispecific CD19 directed CD3
T-cell engagers (BiTE)
Standard of Care

4. BiTE Immunotherapy
Courtesy of Amgen: www.biteantibodies.com
 How BiTE Immunotherapy Works

5. Blinatumomab
 Indications
 Relapse or Refractory B-cell ALL
 Philadelphia Chromosome
 Negative
 Clinical Data
 36 patients – median age 32
 69% - Complete Remission or partial hematologic recovery
 88% - Minimal Residual Disease (MRD)
 No difference observed in overall survival with patients who
underwent HSCT after Blinatumomab monotherapy.

6. Cytokine Release Syndrome
 Inflammatory symptoms resulting from cytokine
elevations associated with T cell engagement and
proliferation.
 Mild – flulike symptoms, low grade fever, myalgia, headache
 Moderate to severe – vascular leak, hypotension, pulmonary edema,
coagulopathy, multi-organ system failure, death
 Prophylaxis and treatment involves reduction of cytokine
levels and blocking action at receptor site.
 Steroids – concern with decreased efficacy or treatment
 Tocilizumab – IL-6 receptor blocker
 IL-2, TNF-α, INF-γ, IL-6, IL-10, IL-4
 Dexamethasone 20 mg IV 1 hour prior to first dose of a
cycle, a step dose, or before restarting after an
interruption of 4 hours or more.

7. Nervous System and Psychiatric Disorders
 CNS events reported in 15-20% of patients treated
with Blinatumomab.
 16 reported CNS events
 8 seizures or convulsions
 6 encephalopathy or confusion
 2 cerebellar symptoms
 All CNS events reversible upon withholding drug
 4/6 re-challenged successfully at lower dose
 Symptoms
 Seizures, difficulty speaking or slurred speech, loss of
consciousness, confusion and disorientation, loss of balance

8. Other Major Adverse Events
 Infection
 33% of patients in phase 2 trial dealt with severe infections
 6 patients died as a result of infections during trials
 B cells undetectable in lass than 2 days
 Leukopenia, hypogammaglobinemia
 Tumor Lysis Syndrome
 Common in acute leukemias
 Characterized by hyperuricemia, hyperkalemia,
hyperphosphatemia, hypocalcemia, acute renal failure,
neuromuscular dysfunction, cardiac dysrhythmias, hematuria.
 Restore electrolyte balance with hydration, diuresis to remove
uric acid, Rasburicase.

9. Clinical Use
 Patient KS (Jan 2015)
 Ataxia
 Complete Remission
 Unique Regimen
 28 dose cycle (min 45 kg)
 Doses 1-7 at 9 mcg/day
 Doses 8-28 at 28 mcg/day
 Patient is hospitalized for first 9 days of the first cycle and first 2
days of the second cycle.
 Cost
 $3178.57/vial x 9 vials
 Billing (DRG) codes 838 vs 837
 $21,561 reimbursement for the total admission
 That’s not good!

10. Prognosis after Blinatumomab therapy

11. Conclusion
 Blinatumomab treatment not only reduces relapse
incidence but also contributes to improved overall
survival. Blinatumomab-induced MRD negativity
translates into relapse free survival.
• BLOOD JOURNAL DECEMBER 20, 2012