Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia

Franklin Reeves, Mercer University College of Pharmacy


Despite marked improvements in outcomes for children with acute lymphoblastic leukemia (ALL), a poor prognosis is noted for adults, with only 30–40% of patients achieving long-term remission and an overall 5-year survival of 10%. As a result, a need for new regimens that yield high complete remission rates with tolerable toxicity profiles was suggested. [1]


Currently, the best chemotherapy regimen is stated to be cytarabine, alclarubicin, and granulocyte colony stimulating factor (CAG), achieving a remission rates as high as 50%. However, more recently, new immunotherapies are indicated as alternative treatment strategies to standard chemotherapy. A Bi-specific T-cell engager (BiTE), blinatumomab, is reported to yield complete remission in 33% of patients with relapsed ALL. With its success, further immunotherapies are suggested to increase current remission rates. [1]

Title: Inotuzumab Ozogamicin versus Standard Therapy for ALL [2]
Design Open-label, two-group, randomized, phase 3 trial; N= 326
Objective To determine whether inotuzumab ozogamicin results in better outcomes in patients with relapsed or refractory ALL than does standard therapy
Study Groups Inotuzumab ozogamicin, standard therapy
Methods Patients in the inotuzumab ozogamicin group received the trial drug intravenously at a starting dose of 1.8 mg per square meter of body-surface area per cycle. Cycle 1 lasted for 21 days and the subsequent cycles each lasted for 28 days; the patients received treatment for up to six cycles. Patients in the standard-therapy group received the investigator’s choice of one of the following three regimens: FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) therapy for up to four 28-day cycles, cytarabine plus mitoxantrone for up to four 15-to-20-day cycles, or high-dose cytarabine for up to one 12-dose cycle. No crossover between groups was allowed. Patients who achieved complete remission could undergo stem-cell transplantation at the investigator’s discretion.
Duration August 2012 to October 2014
Primary Outcome Measure Complete remission
Baseline Characteristics
  Inotozumab Ozogamicin Standard-Therapy
Age (years)    
Median (range) 47 (18-78) 47 (18-79)
Distribution, n (%)    
<55 66 (61) 69 (63)
≥55 43 (39) 40 (37)
Male, n (%) 61 (56) 73 (67)
Response to most recent induction therapy, n (%)    
Complete response 78 (72) 74 (68)
Partial response 9 (8) 7 (6)
Treatment-resistant disease 17 (16) 18 (17)
Progressive or stable disease 4 (4) 10 (9)
  No. of patients Complete remission P-value
Inotuzumab Ozogamicin Standard-Therapy Inotuzumab Ozogamicin Standard-Therapy  
  % (95% Confidence Interval)  
All patients 109 109 80.7 (72.1 to 87.7) 29.4 (21.0 to 38.8) <0.001
Duration of first remission    
<12 months 71 71 77.5 (66.0 to 86.5) 23.9 (14.6 to 35.5) <0.001
≥ 12 months 38 38 86.8 (71.9 to 95.6) 39.5 (24.0 to 56.6) <0.001
Adverse Events
  Inotuzumab Ozogamicin Standard-Therapy
Adverse event (%)    
Nausea 32 47
Headache 28 27
Febrile neutropenia 12 18
Increased aminotransferase level 20 10
Discontinuation 10 40
Study Author Conclusions Treatment with inotuzumab ozogamicin was associated with a higher rate of remission than standard chemotherapy regimens in adults with ALL.


While inotuzumab ozogamicin was able achieve higher rates of remission than standard chemotherapy, remission does not always equate to long-term disease free survival. Future relapse of ALL is common and adults have higher risk of relapse, considering comorbidities and advancing age. In addition, to obtain complete cure, stem cell transplantation is eventually required. As a result, while targeted immunotherapy has garnished well-deserved attention over increased remission rates, continued research should be directed in an effort to increase the cure rate of adults with ALL.



  1. Seiter K. Therapy for relapsed acute lymphoblastic leukemia: Still a role for standard chemotherapy regimens?. Leuk Res. 2016;41:1-2.
  2. Kantarjian HM, Deangelo DJ, Stelljes M, et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016;375(8):740-53.



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