Addition of Bortezomib to Chemo Yields Benefit for Newly Diagnosed Pediatric T-ALL/T-LL

Pediatric patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma experienced an improvement in survival following treatment with bortezomib and chemotherapy.

Treatment with bortezomib (Velcade) and chemotherapy resulted in improved event-free survival (EFS) and overall survival (OS) in pediatric patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL), according to findings from the phase 3 AALL1231 study (NCT02112916).1 Additionally, a large portion of patients with T-cell acute lymphoblastic leukemia (T-ALL) were able to stop prophylactic cranial radiation without excess relapse.

The 4-year EFS rates amongst all patients treated with or without bortezomib were 83.8% ± 2.1% and 80.1% ± 2.3%, respectively (P = .131). Additionally, the 4-year OS rate was 88.3% ± 1.8% in the bortezomib arm versus 85.7% ± 2.0% in the non-bortezomib arm (P = .085). Specifically, patients with T-LL benefited from treatment with bortezomib, with investigators reporting 4-year EFS and OS rates of 86.4% ± 4.0% and 89.5% ± 3.6%, respectively, versus 76.5% ± 5.1% (P = .041) and 78.3% ± 4.9% (P = .009) among those who didn’t receive the agent.

“The results of this trial have the potential to change the standard of care for patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia,” study chair and first author David T. Teachey, MD, an attending physician and director of clinical research at the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia, said in a press release.2 “The data show that most patients with T-ALL no longer need cranial radiation for cure and also suggest bortezomib should be considered as part of the new standard of care for newly diagnosed patients with T-cell lymphoblastic lymphoma.”

The trial included patients with newly diagnosed T-ALL or T-LL who were between the ages of 1 to 30 years. Patients were randomized 1:1 to receive a regimen with or without bortezomib. Those in the experimental arm received 4 doses of bortezomib at 1.3 mg/m2 per block on days 1, 4, 15, and 18. Investigators used an augmented Berlin-Frankfurt-Münster chemotherapy backbone.

A total of 847 patients enrolled on the trial, 615 of whom had T-ALL and 209 had T-LL. Additionally, 408 patients were treated with bortezomib, and 416 patients received chemotherapy alone. Both cohorts of patients had similar characteristics, although more patients in the non-bortezomib arm were male.

Additional findings from the trial indicated that there was no difference in outcomes based on factors such as race, ethnicity, or sex. In the group of patients with T-ALL, 94.3% experienced complete remission. Additionally, in the T-LL group, all patients except 2 were complete responders.

Grade 3 or higher adverse effects occurred in 80.0% of those in the bortezomib arm and 76.5% in the non-bortezomib arm. Twenty patients—10 in each group—died due to infection. Of these deaths, 11 were from invasive fungal disease. Peripheral neuropathy can occur because of treatment with bortezomib, although the overall rate of peripheral neuropathy was predictable and comparable between arms. Fifteen patients in the bortezomib arm and 11 in the non-bortezomib arm experienced grade 4 or higher pulmonary toxicity.

“This is the first trial demonstrating an overall survival benefit for newly diagnosed pediatric T-LL with a small molecule inhibitor,” said senior study author Stephen P. Hunger, MD, who is chief of the Division of Oncology, director of the Center for Childhood Cancer Research, and holder of the Jeffrey E. Perelman Distinguished Chair in the Department of Pediatrics at Children’s Hospital of Philadelphia. “Before this study, the only drugs that have improved survival for [patients with] newly diagnosed T-ALL/T-LL have been cytotoxic chemotherapeutics. The success of bortezomib in this trial could potentially change the approach to frontline treatment of T-LL.”

References

  1. Teachey DT, Devidas M, Wood BL, et al. Children's Oncology Group Trial AALL1231: a phase III clinical trial testing bortezomib in newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma. J Clin Oncol. Published online March 10, 2022. doi:10.1200/JCO.21.02678
  2. CHOP-led study finds bortezomib improves survival in children with newly diagnosed T-cell lymphoblastic lymphoma. News release. Children’s Hospital of Philadelphia. March 10, 2022. Accessed March 11, 2022. https://bit.ly/3pWL7kG