Real-World Experience of Efficacy and Toxicity Issues of Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

Background: In adult patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL), CR rates are low and survival outcomes are very poor. For effective salvage therapy and allogeneic hematopoietic cell transplantation (allo-HCT) in remission, inotuzumab ozogamicin (INO) or blinatumomab (BLIN) have been introduced and revealed their efficacy in clinical trials. We analyzed the treatment outcomes of INO for R/R BCP-ALL patients.

Methods: One hundred patients with R/R BCP-ALL (Ph-positive 25, Ph-negative 75) were treated with a median 2 cycles (range: 1-5) of INO. We applied weekly INO with a dosage of 0.8mg/BSA for first week followed by 0.5mg/BSA for second and third week. For second cycle, we applied 0.5mg/BSA of weekly INO for 3 weeks in patients with complete remission (CR) after first cycle. For post-remission treatment, allo-HCT was planned for all patients.

Results: At the time of INO salvage treatment, 7 (7.0%) were primary refractory (4 BLIN-failure), 36 (36.0%) had relapsed during/after consolidation chemotherapy (23 BLIN-failure), and 57 (57.0%) had relapsed after first (n=47) or second (n=10) previous allo-HCT (23 BLIN-failure). At the time of relapse, bone marrow relapse (BMR) alone was observed in 61 (61.0%) and isolated extramedullary relapse (EMR) in 11 (11.0%), and both BMR+EMR in 28 (28.0%). At the end of first INO cycle, overall response was achieved in 60 (60.0%) patients (57.1% for primary refractory, 61.7% for early relapse < 12 months, and 57.6% for later relapse) and 7 of them underwent allo-HCT. We observed 12 (12.0%) early deaths, 28 non-responders, and 4 of them discontinued INO due to VOD/SOS and infectious complications. At the end of second INO cycle, best response was observed in 67 (67.0%) with MRD response of 63.1% and among them, 39 (58.2%) underwent allo-HCT. Among the rest 28 responders, 9 died in CR (2 VOD/SOS, 7 sepsis), 16 relapsed, and 3 are alive in CR after INO consolidation. Follow-up duration was median 24 months (range 8.5-53.5), and 2-year OS was 20.4%, and patients treated with allo-HCT showed 37.7% of 1-year OS.

Conclusion: Our data suggested that INO can be a feasible choice for salvage for adults with R/R BCP-ALL which showed a good CR rate. However, we experienced unexpectedly high regimen-related mortality caused by hepatotoxicity and infectious complications or thrombocytopenia due to marrow suppression. Risk-adapted dose adjustment or patient selection for INO are important for better treatment outcomes.

Park:ImpriMed, Inc.: Consultancy, Current holder of stock options in a privately-held company. Kim:Jazz Pharmaceuticals, Takeda, Astellas, AbbVie and APLC: Other: Travel; AbbVie, Astellas, BMS, Handok, Novartis, AML-Hub, Jazz Pharmaceuticals and Takeda: Honoraria, Speakers Bureau; BL&H: Research Funding; AML-Hub, APBMT, ICBMT, APLC, Novartis and BMS: Other: and leadership or fiduciary roles in other board, society, committee or advocacy group ; BMS & Celgene, Novartis, APLC, AbbVie, Astellas, Janssen, Handok, Pfizer, Sanofi Genzyme, AML-Hub, Daiichi Sankyo and APBMT: Membership on an entity's Board of Directors or advisory committees; AbbVie, AIMS Bioscience, AML-Hub, Astellas, BMS & Celgene, Boryung Pharm Co., Daiichi Sankyo, Janssen, Handok, LG Chem, Novartis, Pfizer, SL VaxiGen, VigenCell, Aston Bioscience, Ingenium, Amgen, Sanofi Genzyme, Takeda, Meiji Pharm Co. and GreenCross Phar: Consultancy.