Blinatumomab as salvage therapy in patients with relapsed/refractory B-ALL who have failed/progressed after anti-CD19-CAR T therapy

Ann Med. 2023 Dec;55(1):2230888. doi: 10.1080/07853890.2023.2230888.

Abstract

Background: Anti-CD19 chimeric antigen receptors (CARs) T-cell therapy has been shown to have excellent efficacy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). But many patients are refractory to anti-CD19-CAR T-cell therapy or relapse again.

Methods: Five patients with R/R B-ALL did not respond to anti-CD19-CAR T-cell therapy or had a disease progression again after CAR-T cell therapy. They received a salvage therapy of Blinatumomab. The clinical response, CD19 expression on ALL cells, the proportion of CD3+ T cells, level of cytokine levels of interleukin-6 (IL-6), hematological toxicity, grade of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxic syndrome (ICANS) were observed in salvage therapy of Blinatumomab.

Results: Four patients obtained CR/CRi, even in patients without high expression of CD19 in B-ALL cells, while the other patient received NR after Blinatumomab therapy. The CD19 expression on ALL cells, the proportion of CD3+ T cells, and CD3+CD8+ T cells were deficient in Pt 5, who obtained PR in Blinatumomab therapy. One patient (Pt 3) was diagnosed with grade 0 hematological toxicity. The other four patients were diagnosed with grades 2-3 of hematological toxicity. The CRS was grade 0/one patient, grade 1/three, and grade 2/one. The ICANS was grade 0/four patients, grade 1/one. Rhizopus microsporus pneumonia and cryptococcal encephalopathy in two patients were controlled during Blinatumomab therapy.

Conclusions: Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in R/R B-ALL patients without high expression of CD19 in B-ALL cells, patients with CNS leukemia or co-infection.Key messagesSome R/R B-ALL patients did not respond to anti-CD19 CAR T-cell therapy or had a disease progression again. Effective and safe salvage therapy for such patients remains to be explored.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients without high expression of CD19 in B-ALL cells.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients with CNS leukemia or co-infection.

Keywords: B-cell acute lymphoblastic leukemia; anti-CD19-CAR T therapy; blinatumomab; salvage therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific* / therapeutic use
  • Antigens, CD19
  • CD8-Positive T-Lymphocytes
  • Coinfection* / drug therapy
  • Coinfection* / etiology
  • Disease Progression
  • Humans
  • Immunotherapy, Adoptive
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Receptors, Chimeric Antigen / therapeutic use
  • Salvage Therapy*

Substances

  • Antigens, CD19
  • blinatumomab
  • Receptors, Chimeric Antigen
  • Antibodies, Bispecific

Grants and funding

This work was partially supported by the Chinese Society of Clinical Oncology Beijing Xisike Clinical Oncology Research Foundation (Y-SY2021QN-0184). Chinese Society of Clinical Oncology Beijing Xisike Clinical Oncology Research Foundation (Y-Young2022-0209). The National Natural Science Foundation of China (81900186). Tianjin Municipal Science and Technology Commission Grant (20JCZDJC00120 and 21JCQNJC00070). The CAMS Innovation Fund for Medical Science (NO.2020-I2M-C&T-A-019).