Emerging biological therapies to treat acute lymphoblastic leukemia.
Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered: Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented. Rituximab, a naked anti-CD20 MoAb, improves the results of chemotherapy in Philadelphia chromosome-negative BCP-ALL. Inotuzumab ozogamicin, an anti-CD22 immunotoxin, yields complete remission (CR) rates of 80% in R/R patients and in elderly newly diagnosed patients. Blinatumomab, a bispecific anti-CD19 and anti-CD3 agent redirects effector T cells towards B leukemic cells, is approved in R/R patients (40% CR, duration 6 months) and under investigation in MRD+ CR patients (80% negativation). Autologous anti-CD19 CAR-T cells undergo proliferation and persistence in the recipient. In limited series, they salvage more than 80% of advanced patients. Cytokine-release syndrome, encephalopathy and B-cell aplasia are shared, to varying extents, by blinatumomab and CAR-T cells. Expert opinion: Despite technological, ethical and clinical issues, biological therapies are currently changing the paradigm of treatment in BCP-ALL, and seem promised to dramatic developments.
a Hematology , University Cancer Institute , Toulouse , France.
Françoise
F
Huguet
a Hematology , University Cancer Institute , Toulouse , France.
Suzanne
S
Tavitian
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001691:Biological Therapy / Q000379:methods; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
Acute lymphoblastic leukemia; CAR-T cells; adoptive immunotherapy; biological therapies; blinatumomab; inotuzumab ozogamicin; monoclonal antibodies; rituximab