- ONCOLOGY Vol 26 No 9
- Volume 26
- Issue 9
Treatment of Adult Acute Lymphoblastic Leukemia (ALL) With a Focus on Emerging Investigational and Targeted Therapies
In this review, we will discuss the management of ALL in the adult population, in the context of the recently published guidelines from the NCCN. We will focus in particular on the strides being made in salvage and targeted approaches.
Acute lymphoblastic leukemia (ALL) in adults is a very challenging disease. Adults tend to present with higher-risk features and are unable to tolerate chemotherapy regimens as intense as those administered to children. The overall treatment plan for adult ALL is modeled after the pediatric paradigm and includes multi-agent chemotherapy in the forms of induction, consolidation, maintenance, and central nervous system prophylaxis. Most patients will go into complete remission but often relapse; relapse is typically indicative of chemotherapy-refractory disease. Salvage therapy generally consists of cytotoxic agents from drug classes the patient has had limited or no exposure to. The results of conventional chemotherapy for relapsed ALL are unacceptable. The goal of therapy in these patients is to achieve a second remission followed by allogeneic stem-cell transplantation. Monoclonal antibodies directed at cell-surface antigens offer a targeted approach to treating leukemia and other cancers. Anti-CD20 monoclonal antibodies have been shown to improve survival when used in the frontline setting. Novel, highly active antibodies directed at CD19 and CD22 are being investigated in the relapsed and refractory settings. These agents will likely be explored as components of first-line therapy as clinical development continues.
Introduction
Acute lymphoblastic leukemia (ALL) is a heterogeneous disease characterized by the accumulation and proliferation of clonal lymphoid progenitor cells in the bone marrow, periphery, and/or extramedullary sites. The disease is expected to be diagnosed in 6,050 individuals in 2012, with a higher proportion of the diagnoses in children.[1] While ALL is known as a cancer success story in the pediatric setting, with cure rates approaching 90%,[2] the same cannot yet be said of adults. Historically, cure rates for adult ALL are approximately 20% to 40%,[3] depending on patient age and disease characteristics, although these numbers may be improving in younger adults treated with regimens that incorporate targeted therapies.[4] Patients who are at a particularly high risk for a poor outcome include those with rearrangements involving the mixed lineage leukemia (MLL) gene, or with Philadelphia chromosome (Ph)-positive disease. These subtypes occur at a much higher frequency in adults than they do in children. Adults are also far less likely to have favorable cytogenetic features at diagnosis, such as t(12;21) or hyperdiploidy. Unfortunately, most patients will achieve complete remission (CR), and then subsequently suffer a relapse. Salvage regimens for ALL are improving, and targeted therapies are currently being examined in clinical trials. In this review, we will discuss the management of ALL in the adult population, in the context of the recently published guidelines from the National Comprehensive Cancer Network (NCCN).[5] We will focus in particular on the strides being made in salvage and targeted approaches.
FIGURE 1
Outcomes of Frontline HyperCVAD According to Risk Category