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Acute lymphoblastic leukemia in adults: encouraging developments on the way to higher cure rates.

ABSTRACT: Conventional cytotoxic chemotherapy for adult acute lymphoblastic leukemia (ALL) is not adequate to cure most patients of the disease. Complete remission is achieved in the majority of patients, but responses are often not durable. Allogeneic stem cell transplant is used for patients with high risk features, including those who are positive for minimal residual disease after induction and consolidation therapy. Nevertheless, transplant is a toxic intervention, and does not guarantee long-term disease-free survival. Monoclonal antibodies target surface antigens present on leukemic blasts, with the aim of minimizing off-target toxicity. Rituximab, an antibody directed against CD20, prolongs the survival of younger adults with ALL when added to chemotherapy in the frontline setting. Novel agents, such as the cytotoxin-antibody conjugate inotuzumab, and the bispecific T-cell engaging compound blinatumomab, have exhibited marked antileukemic activity in the relapsed setting. As these agents continue in clinical development, it will be important to eventually incorporate them in the frontline treatment approach. We review current strategies for treating adult ALL, with a focus on novel and targeted therapies that are under development.

SUBMITTER: Mathisen MS

PROVIDER: S-EPMC5681222 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Acute lymphoblastic leukemia in adults: encouraging developments on the way to higher cure rates.

Mathisen Michael S MS Kantarjian Hagop H Thomas Deborah D O'Brien Susan S Jabbour Elias E

Leukemia & lymphoma 20130621 12

Conventional cytotoxic chemotherapy for adult acute lymphoblastic leukemia (ALL) is not adequate to cure most patients of the disease. Complete remission is achieved in the majority of patients, but responses are often not durable. Allogeneic stem cell transplant is used for patients with high risk features, including those who are positive for minimal residual disease after induction and consolidation therapy. Nevertheless, transplant is a toxic intervention, and does not guarantee long-term di ...[more]

PMID: 23547835

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Project description:BackgroundMany older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.MethodsIn a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point.ResultsThe data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group.ConclusionsThe addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).

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Acute lymphoblastic leukemia in adults: encouraging developments on the way to higher cure rates.

Publications

Acute lymphoblastic leukemia in adults: encouraging developments on the way to higher cure rates.

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