Bortezomib extends survival of children with newly diagnosed T-cell lymphoblastic lymphoma
Click Here to Manage Email Alerts
The addition of bortezomib to chemotherapy significantly improved survival outcomes among children and young adults with T-cell lymphoblastic lymphoma, according to phase 3 study results published in Journal of Clinical Oncology.
Additionally, radiation can be eliminated in 90% of children with T-cell acute lymphoblastic leukemia with the intensified chemotherapy regimen, researchers noted.
Rationale and methods
“The cure rate for children and young adults with [T-cell acute lymphoblastic leukemia] and [T-cell lymphoblastic lymphoma] has improved significantly during the past 30 years. Nevertheless, patients with relapsed disease have poor outcomes and are rarely salvaged,” David T. Teachey, MD, attending physician and director of clinical research at Center for Childhood Cancer Research at Children’s Hospital of Philadelphia, told Healio. “Thus, the primary goal in the treatment of T-ALL and T-LL is to identify novel effective agents and move them to the front line and prevent relapse.”
A strong biologic rationale exists for targeting the proteasome in T-ALL and T-LL, Teachey said. Moreover, bortezomib (Velcade, Millennium/Takeda), a proteasome inhibitor, has shown promise in early-phase trials among patients with relapsed and refractory disease. “Thus, we moved bortezomib to the front line in a randomized trial,” he said.
Teachey and colleagues randomly assigned 824 children and young adults with T-ALL (n = 615) or T-LL (n = 209) enrolled between 2014 and 2017 to a modified Berlin-Frankfurt-Münster chemotherapy regimen, which included dexamethasone instead of prednisone and the addition of two extra doses of pegaspargase, with or without bortezomib during induction and delayed intensification.
Key findings
Overall, results showed the bortezomib group, compared with the chemotherapy-alone group, had numerically but not statistically significantly higher rates of 4-year EFS (83.8% vs. 80.1%) and 4-year OS (88.3% vs. 85.7%). However, among those with T-LL, researchers observed significant improvements with bortezomib in 4-year EFS (86.4% vs. 76.5%; P = .041) and 4-year OS (89.5% vs. 78.3%; P = .009).
Researchers noted no new adverse events with bortezomib.
Implications
“Bortezomib is an active drug in T-LL and should be considered for children with relapsed T-LL who have not been treated with bortezomib. For newly diagnosed children with T-LL, we need to strongly consider making bortezomib part of the new standard-of-care therapy,” Teachey said. “Using modern chemotherapy backbones, the majority of children with T-ALL can be cured without radiation, which has huge implications as radiation leads to cognitive impairment and secondary malignancies. Children who received cranial radiation when young have higher mortality rates then the general population and increased unemployment.”
Future research is needed to better understand why bortezomib significantly improved cure rates in T-LL but not T-ALL, Teachey added.
“We have ongoing correlative biology studies dedicated to answering this question. Some children with T-ALL treated on AALL1231 did have improved outcomes with bortezomib and we need to understand who these children are and why. We also need to figure out the best way to include bortezomib in future clinical trials,” Teachey said. “Finally, while we need to figure out ways to eliminate cranial radiation in all children with T-ALL, it is also important to highlight that the only way this type of trial can happen is through cooperative groups. Childhood cancers are rare, and most children are cured overall. Thus, we need multicenter collaborative efforts, and as outcomes continue to improve in childhood malignancies, we are also going to have to move toward more international collaborations.”
For more information:
David T. Teachey, MD, can be reached at Children’s Hospital of Philadelphia, 3008 CTRB, 3501 Civic Center Blvd., Philadelphia, PA 19104; email: teacheyd@email.chop.edu.
Collapse
Click Here to Manage Email Alerts