Tailored Treatment Boosts Prognosis in High-Risk T-cell ALL

Roxanne Nelson

December 09, 2014

SAN FRANCISCO — It is axiomatic that tailoring cancer treatment to the individual can improve outcomes.

But that is not always easy, especially in patients with a difficult-to-treat cancer such as high-risk subtypes of T-cell acute lymphoblastic leukemia (T-ALL).

T-ALL has sometimes been associated with a poor prognosis, and it is generally worse for patients with a specific protein signature called the early thymic precursor (ETP) immunophenotype.

But new data, presented during the plenary session here at the American Society of Hematology 56th Annual Meeting, show that patients with this subtype can achieve the same outcomes as other T-ALL patients when treatment is individualized to their risk.

Even though patients with ETP T-ALL had a higher incidence of residual disease after therapy initially, overall survival was similar in patients with and without the ETP subtype, said lead study author Brent Wood, MD, PhD, from the University of Washington in Seattle.

Dr Brent Wood

"This is the first large trial to demonstrate that patients with ETP T-ALL may have an outcome similar to that of other patients with this disease," he told Medscape Medical News.

The Children's Oncology Group AALL0434 trial is the largest study ever conducted in T-ALL, Dr Wood explained. It involved 1144 patients 1 to 30 years of age.

Patients were treated with a standard four-drug induction. After response-based risk stratification on day 29, intermediate- and high-risk patients were randomized to receive or not receive six 5-day courses of nelarabine during the consolidation, delayed intensification, and maintenance phases.

Early Stratification

Risk stratification involved the detection of minimal residual disease (MRD) with flow cytometry in peripheral blood on day 8 and in bone marrow on day 29. MRD below 0.1% was considered to be low risk, below 1.0% was considered to be intermediate risk, and above 1.0% was considered to be high risk.

In the cohort, 11.3% of the T-ALL patients had the ETP immunophenotype, 17.0% had an immunophenotype related to ETP and were classified as near-ETP, and 71.6% had a non-ETP immunophenotype.

At the end of the induction phase, there was a "notable statistical difference" in the level of MRD detected in the three groups. The rate of low-risk patients was lower in the ETP group than in the near-ETP and non-ETP groups (18.6% vs 35.2% vs 69.5%). In addition, rates of induction failure were significantly higher in the ETP and near-ETP groups than in the non-ETP group (7.8% vs 6.7% vs 1.1%; P < .0001).

In addition, an initial white blood cell count of at least 200,000/μL was associated with a worse outcome than a count below 200,000/μL.

But despite these differences in induction failure and MRD, event-free survival and 5-year overall survival were essentially the same in the three groups, Dr Wood reported.

Five-year event-free survival was 87.0% for patients in the ETP group, 84.4% for those in the near-ETP group, and 86.9% for those in the non-ETP group. Rates of 5-year overall survival were similar in the three groups (93% vs 91.6% vs 92%).

"After about the first year or two, there really is no difference between the ETP subsets," said Dr Wood. "The poor ETP status that had been previously described for this subtype appears to have been eradicated by the therapies used in the AALL0434 trial."

Event-free survival was worse when MRD in the bone marrow was intermediate or high risk than when it was low risk (76.3% vs 89.0%; P = .0001), as was overall survival (86.6% vs 93.8%; P = .0008). The proportion of patients classified as intermediate or high risk was 81.4% in the ETP group, 64.8% in the near-ETP group, and 30.5% in the non-ETP group.

All patients had similar outcomes, despite differences in MRD after induction, and the incidence of induction failure was higher in the EPT and near-ETP groups.

"The study also demonstrates the utility of using post-therapeutic monitoring disease detection that was able to stratify patients in terms of risk at the end of induction at day 29," Dr Wood explained. "It emphasized the benefit of stratifying patients by MRD at the end of induction and the end of consolidation."

Two Essential Points

This study has two important points, said Karen Ballen, MD, director of the leukemia program at the Massachusetts General Hospital in Boston. "One is that a high white count is associated with a poorer outcome," she said. "Previously we thought 100,000/μL was a cutoff, but that may be changing."

"Also important was looking at patients at day 8 to see if they have minimal residual disease; those patients usually end up doing worse," she told Medscape Medical News. "They need to be risk-stratified to have more aggressive therapy."

"It's a very large study of a rare disease, so I congratulate the authors," Dr Ballen added.

American Society of Hematology (ASH) 56th Annual Meeting: Abstract 1. Presented December 7, 2014.


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