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In recent years, there have been attempts to use more intensive chemotherapy, inspired by those used in pediatric patients, in adolescent and young adult (AYA) patients with B‑cell ALL. These regimens derived from pediatric protocols include more intensive use of corticosteroids, vincristine, as well as asparaginase. They also emphasize timely administration of therapy with less time between treatment cycles and use MRD quantification to determine the next steps of therapy. The pediatric-inspired regimens have been studied by a variety of groups in the United States and Europe and have consistently demonstrated better outcomes than conventional adult regimens in AYA patients.
A typical regimen for ALL consists of induction therapy, consolidation or early intensification, an interim maintenance phase, a course of delayed intensification, followed by another consolidation and a final prolonged course of maintenance. As mentioned, pediatric regimens involve more intensive use of corticosteroids, vincristine, and asparaginase. Therefore, these regimens are usually quite intensive upfront and prolonged, requiring a rigorous approach to maintain patients on schedule for therapy. For patients with Ph-positive diseases, a BCR/ABL tyrosine kinase inhibitor (TKI) is usually added to the various regimens.
The Intergroup C10403 study examined a pediatric-like regimen in AYA patients with ALL. Among 295 evaluable patients, the 3-year EFS rate was 59% with a median EFS of 78 months compared with historical control of 30 months. The 3-year OS rate was 73% and the median OS was not reached. These results represent very promising outcomes in this patient population, particularly compared with conventional regimens previously used in similar populations.
Other approaches to the treatment of ALL include the addition of targeted therapies such as rituximab to conventional therapies. A subset of patients with B‑cell ALL expresses the protein CD20 on the cell surface; consequently, rituximab, a CD20 antibody, has been combined with traditional chemotherapies for CD20-expressing B‑cell ALL. In a study conducted at the MD Anderson Cancer Center, 282 patients with CD20-positive B-cell ALL received hyper-CVAD plus rituximab. Both CR duration and OS were significantly improved by the addition of rituximab to hyper-CVAD.
More recently, InO, an ADC targeting CD22, was combined with mini‑hyper-CVD, a less intensive version of hyper-CVAD, in 52 patients older than 60 years of age with Ph-negative ALL in a single-arm phase II study. Both the PFS and OS outcomes were quite promising with a 3-year OS rate of 56%, which compared favorably vs the historical values in patients treated with hyper-CVAD.
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