Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden

• Published in: Blood cancer journal (New York) Vol. 10; no. 8; p. 81
• Main Authors: DeAngelo, Daniel J., Advani, Anjali S., Marks, David I., Stelljes, Matthias, Liedtke, Michaela, Stock, Wendy, Gökbuget, Nicola, Jabbour, Elias, Merchant, Akil, Wang, Tao, Vandendries, Erik, Neuhof, Alexander, Kantarjian, Hagop, O’Brien, Susan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.08.2020; Springer Nature B.V
• Subjects: 631/67/1059/602; 631/67/1990/283/2125; 692/699/1541/1990/283/2125; Acute Disease; Adult; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow - drug effects; Bone Marrow - pathology; Cancer; Cancer Research; Chemotherapy; Hematology; Humans; Immunotherapy; Inotuzumab Ozogamicin - adverse effects; Inotuzumab Ozogamicin - therapeutic use; Kaplan-Meier Estimate; Leukemia; Medical prognosis; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Researchers; Statins; Targeted cancer therapy; Treatment Outcome
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-020-00345-8

Adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) have a poor prognosis, especially if disease burden is high. This post hoc analysis of the phase 3 INO-VATE trial examined the efficacy and safety of inotuzumab ozogamicin (InO) vs. standard of care chemotherapy (SC) among R/R ALL patients with low, moderate, or high disease burden, respectively, defined as bone marrow blasts (BMB) < 50% ( n  = 53 vs. 48), 50–90% ( n  = 79 vs. 83), and >90% ( n  = 30 vs. 30). Patients in the InO vs. SC arm with low, moderate, and high BMB%, respectively, had improved rates of complete remission/complete remission with incomplete hematologic recovery (74% vs. 46% [ p  = 0.0022], 75 vs. 27% [ p  < 0.0001], and 70 vs. 17% [ p  < 0.0001]), and improved overall survival (hazard ratio: 0.64 [ p  = 0.0260], 0.81 [ p  = 0.1109], and 0.60 [ p  = 0.0335]). Irrespective of BMB%, cytopenias were the most common treatment-emergent adverse events, and post-transplant veno-occlusive disease was more common with InO vs. SC. Patients with extramedullary disease or lymphoblastic lymphoma showed similar efficacy and safety outcomes. This favorable benefit-to-risk ratio of InO treatment irrespective of disease burden supports its use in challenging and high disease burden subpopulations. INO-VATE is registered at www.clinicaltrials.gov : #NCT01564784. Plain language summary Acute lymphoblastic leukemia (ALL for short) is a type of blood cancer where the body makes too many immature white blood cells called lymphoblasts. This study involved people with ALL whose cancer had returned after, or stopped responding to, previous treatment. These people received either inotuzumab ozogamicin (InO for short) or standard chemotherapy. Researchers divided people into groups, based on the level of lymphoblast cells they had in their bone marrow (called disease burden): low, medium, or high disease burden. In this study, compared with people who received standard chemotherapy, people who received InO were more likely to have no signs of their cancer (called remission), live to the end of the study, and/or reach the end of the study without their cancer getting worse. The researchers saw these results across all disease burden groups. For people who received InO, those with high disease burden were equally as likely as those with low disease burden to achieve remission, and/or experience medical problems. For people who received standard chemotherapy, those with high disease burden were less likely than those with low disease burden to achieve remission. Further information in a plain language format is available in Supplementary Information (SI) Fig. S1.