Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab

Abstract

<jats:sec><jats:title>Introduction</jats:title><jats:p> Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47–241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted. </jats:p></jats:sec>

Case report: atypical, unilateral optic nerve infiltration as the first sign of acute lymphoblastic leukemia (ALL) relapse

“…Blinatumomab is a bispecific antibody binding simultaneously to CD19 on the surface of B-cells and CD3 on the surface of T-cells leading to tumor cell lysis [ 12 ]. Compared to standard chemotherapy, Blinatumomab has shown promising results regarding long term survival in a randomized, multi-center trial [ 13 ] and is approved for the treatment of B-cell ALL [ 12 ]. Box warnings of Blinatumomab include neurological symptoms such as encephalopathy, convulsions, speech disorders, delirium, and balance disorders.…”

An Unusual Presentation of Extramedullary Relapse Following Blinatumomab in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

“…Sites of EMR included the CNS, kidney, lymph node, muscle, chest wall, and nasopharynx. In another recent study by Lau et al including adult patients with R/R B-ALL or with minimal residual disease positive and treated with blinatumomab, the EMR rate was 20% and included lymph nodes, pancreas, adrenal gland, kidneys, liver, left parotid gland, and brain [ 12 ]. In our case, the patient presented multiple EMR sites.…”

Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors

“…Unfortunately, most patients still relapse eventually after primary response to blinatumomab therapy. These relapses are currently being extensively investigated and the data have thus far indicated that relapses are frequently found at immune-privileged extramedullary locations and some relapses have lost CD19 antigen expression, but more research is required to further elucidate these resistance mechanisms [ 18 , 19 ].…”