Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

Abstract

Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involvement. Response to treatment may be unique. We evaluated response to inotuzumab ozogamicin (INO) in 31 relapsed/refractory (r/r) BALL patients with extramedullary disease (EMD). Median age was 31 (range, 19-81) years. All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (allo-HCT; n=18). Overall response rate after two INO cycles was 84% (complete remission (CR), 55%; partial remission (PR), 29%; resistant disease (PD), 13%; early death, 3%). Median follow-up was 29 months and median overall survival (OS) 12.8 months. One-year and 2-year OS rates were 53% (95%-CI, 37-76%) and 18% (95%-CI, 8-43%), respectively. Age had no impact on OS when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allo-HCT (CR, n=6; PR, n=3; PD, n=3). Prior to allo-HCT, eight patients received ≤2 and four patients 3-4 INO cycles. Sinusoidal obstruction syndrome was reported in three patients, including one after transplant. Allo-HCT evaluated as a time-dependent variable had no impact on OS. INO seems to be effective as debulking strategy in r/r-ALL with EMD. However, INO followed by allo-HCT seems not to be effective in maintaining long term disease control.

Sequencing antigen‐targeting antibodies and cellular therapies in adults with relapsed/refractory B‐cell acute lymphoblastic leukemia

“…49 In a retrospective analysis of 31 adults with r/r B-ALL or lymphoid blast crisis with non-CNS EMD, the CR rate was 55%, with 2-year OS of 18%. 53 Furthermore, 4 out 59 inotuzumab responders and 2 out of 41 SOC responders relapsed with EMD. 49 In contrast to blinatumomab, inotuzumab appears to have potential activity in ALL with EMD, without excessive risk of EMD relapse after response.…”

“…In a post‐hoc analysis of the INO‐VATE study in patients with baseline non‐CNS EMD, CR/CRi was reported in five out of seven patients treated with inotuzumab and two out of five patients treated with standard of care (SOC) 49 . In a retrospective analysis of 31 adults with r/r B‐ALL or lymphoid blast crisis with non‐CNS EMD, the CR rate was 55%, with 2‐year OS of 18% 53 . Furthermore, 4 out 59 inotuzumab responders and 2 out of 41 SOC responders relapsed with EMD 49 .…”

“…Extramedullary relapse is a difficult scenario in ALL management, as the efficacy of conventional therapy is limited, particularly if the relapse occurs in the CNS. EMD failure is encountered excessively during blinatumomab therapy, and data for the use of inotuzumab in ALL with EMD are limited 49,53 . Isolated EMD relapse and CNS involvement in ALL are frequent exclusion criteria in clinical studies, leading to limited therapeutic options in r/r patients.…”

“…EMD failure is encountered excessively during blinatumomab therapy, and data for the use of inotuzumab in ALL with EMD are limited. 49,53 Isolated EMD relapse and CNS involvement in ALL are frequent exclusion criteria in clinical studies, leading to limited therapeutic options in r/r patients. In contrast, CD19 CAR T-cell therapy produces high response rates in relapsed ALL with EMD as discussed previously.…”

Results of the compassionate program of inotuzumab ozogamicin for adult patients with relapsed or refractory acute lymphoblastic leukemia in Spain

“…Subanalyses in the INOVATE trial showed that the benefits of IO were more evident if used as first salvage therapy, 10 especially for patients who achieved negative measurable residual disease (MRD) 11 . Other studies demonstrated the benefit of IO even in B‐ALL patients irrespective of disease burden and in patients with disease with extramedullary involvement or B‐cell lymphoblastic lymphoma 12–14 …”