Safety and Efficacy Results of Dose-Adjusted Inotuzumab Ozogamicin in Adults with B Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Experience

Introduction: Inotuzumab ozogamicin (InO) is a CD22-directed antibody-drug conjugate indicated for refractory or relapsed (R/R) B cell acute lymphoblastic leukemia(B-ALL). The efficacy and safety of its single and combination regimens have been confirmed in several clinical trials across different phases of treatment, including frontline induction, minimal residual disease (MRD) clearance, salvage therapy, and so forth. Given the high cost of InO, the dose was adjusted to 1 mg (approximately 0.6 mg/m²) per administration, with individual adjustments made at our center to enhance patient accessibility and affordability. In this study, we present a summary of real-world data on the treatment patterns, effectiveness, and safety of InO in Chinese patients with newly diagnosed (ND), MRD-positive, and R/R B-ALL.

Methods: In this retrospective observational study, data on B-ALL patients who received at least one dose of InO in frontline and MRD-positive, R/R settings between June 2019 and April 2023 were collected from the electronic medical records of our center. Intravenous INO was given one or more doses at 1mg (approximately 0.6mg/m²), as a single agent or in combination with other anti-leukemia drugs. For Ph-negative patients, 9 received a single agent regimen and 15 received InO plus chemotherapy regimen. For Ph-positive patients, 15 received InO+TKI regimen and 5 received InO plus chemotherapy and TKI regimen. We report the response rate, incidence of adverse events, and overall survival (OS). OS was defined as the time from the initiation of InO to death from any cause.

Results: Of the 44 enrolled patients, 12 received frontline treatment (InO for frontline remission induction: n = 3; frontline consolidation or maintenance: n = 9), 19 received for MRD, and 13 received treatment in R/R setting (InO for re-induction: n = 13). Intravenous InO was given one or more doses at 1mg (approximately 0.6mg/m²).

In the ND group, 7 and 5 patients were Ph-positive and Ph-negative; 3 and 9 patients were standard risk(SR) and high risk(HR) for relapse. For patients receiving VIC(L)P combined with InO as frontline induction, the median dose of InO was 1(range: 1~3); all achieved complete remission (CR) and 2/3 patients achieved MRD negative. The median time to remission was 27(19-41) days. For patients receiving InO as part of consolidation or maintenance (InO+/-TKI, n=6; InO+VP+/-TKI,n=2; InO+ venetoclax + chidamide, n=1), the median dose of InO was 2(range: 1~5). Four patients underwent autologous hematopoietic stem cell transplantation(autoHSCT), while 2 patients underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). All are still alive, with 2 patients having experienced relapses. The one-year OS rate was 88.9±10.5%.

In the MRD group, 10 and 9 patients were Ph-positive and Ph-negative, and all were classified as HR. Eighteen (94.7%) patients were with extramedullary diseases. The median dose of InO was 2 (range: 1-4). The median time to remission was 28 (range: 14-71) days. Sixteen (84.2%) patients turned MRD negative with 12 of these patients undergoing HSCT ( 3 auto-, 9 allo-). 1-year OS rate was 91.7±8.0%.

In the R/R group, 6 and 7 patients were Ph-positive and Ph-negative; all were HR. Three (94.7%) patients had extramedullary diseases. The median dose of InO was 2 (range: 1-3) and the median time to remission was 30 (range: 16-78) days. Eight (61.5%) patients achieved CR/CRi, 5 of whom achieved MRD negative. After that, 7 patients received alloHSCT, and 4 were second HSCT. 1-year OS rate was 36.9±13.8%.

During InO treatment, AEs of any grade were reported in 79.5% of patients (35/44). Hematological toxicities were observed in 79.5% (35/44) of patients. Hepatic toxicities were observed in 29.5% (13/44) of patients, and only 2 patients experienced G3/4 hepatic toxicities. No veno-occlusive disease (VOD) occurred during InO treatment or in the post-transplantation period.

Conclusions: The results of this study indicate that dose-adjusted InO is a well-tolerated and effective treatment option for B-ALL adults with or without chemotherapy or TKI. It can be employed as a frontline induction, consolidation, maintenance and MRD clearance, and salvage therapy. Given the limited real-world data, further studies are essential to determine its long-term survival benefit and investigate better combination therapy to guide physicians in making evidence-based clinical decisions.