Bortezomib Shows Survival Benefit in Children With T-Cell Lymphoblastic Lymphoma

The AALL1231 trial of bortezomib showed survival benefit for children with T-cell lymphoblastic lymphoma and significantly reduced need for cranial radiotherapy in patients with T-cell acute lymphoblastic leukemia.

Bortezomib (Velcade) was found to have event-free survival (EFS) and overall survival (OS) benefit in children with T-cell lymphoblastic lymphoma (T-LL) but not in the full study population with T-LL or T-cell acute lymphoblastic leukemia (T-ALL), according to findings from the Children’s Oncology Group published in the Journal of Clinical Oncology.1

Results from the AALL1231 trial (NCT02112916) showed that patients with T-LL who received bortezomib plus chemotherapy had 4-year EFS of 86.4% ± 4.0% versus 76.5% ± 5.1% with chemotherapy alone (P = .041). The 4-year OS was 89.5% ± 3.6% versus 78.3% ± 4.9% with bortezomib or without bortezomib, respectively (P = .009). This trial also showed that cranial radiotherapy (CRT) can be avoided in most patients with T-ALL. However, the overall results for patients across both disease types did not show statistically significant benefit to EFS.

“The results of this trial have the potential to change the standard of care for patients with T-LL and T-ALL,” 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, stated 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-LL.”

The phase 3 AALL1231 study randomized 824 patients with newly diagnosed T-ALL or stage II to IV T-LL 1:1 to receive chemotherapy with or without bortezomib. The treatment was modified from the augmented Berlin-Frankfurt-Münster regimen used in the previous phase 3 AALL0434 trial (NCT00408005) of nelarabine (Arranon) in T-ALL by including dexamethasone instead of prednisone and adding 2 extra doses of pegaspargase (Oncaspar) to reduce the need for CRT, which can have serious long-term adverse events (AEs) in children.1

In AALL0434, 90.8% of patients with T-ALL received CRT, while in AALL1231, only 9.5% were scheduled to receive CRT.1,3 There was no statistically significant difference in EFS for patients who did not receive CRT in AALL1231 versus comparable patients who did receive CRT in the AALL0434 trial (P = .412); the same was true of OS (P = .600).

Currently, 5-year OS for patients with T-ALL and T-LL is approximately 85%, but less than 35% of patients survive a relapse, making more intensive frontline therapy a major area of study in preventing relapse.2

Though there were favorable survival outcomes for patients with T-LL, those with T-ALL did not show statistically significant improvement. The overall results for patients with both disease types showed that those receiving bortezomib had an EFS of 83.8% ± 2.1% versus 80.1% ± 2.3% without bortezomib (P = .131).1

“This is the first trial demonstrating an OS benefit for newly diagnosed pediatric T-LL with a small molecule inhibitor,” senior study author Stephen P. Hunger, MD, 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, said in a statement.2 “Before this study, the only drugs that have improved survival for newly diagnosed [patients with] T-ALL/T-LL have been cytotoxic chemotherapeutics.”

No excess toxicity from bortezomib was reported in the trial. With the significant benefit to EFS and OS in T-LL, bortezomib could improve outcomes for many patients with this form of childhood lymphoma.

“The success of bortezomib in this trial could potentially change the approach to frontline treatment of T-LL,” Hunger concluded.

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. Children’s Hospital of Philadelphia. Published March 10, 2022. Accessed March 14, 2022. https://bit.ly/3w5ANuB

3. Dunsmore KP, Winter SS, Devidas M, et al. Children's Oncology Group AALL0434: a phase III randomized clinical trial testing nelarabine in newly diagnosed T-cell acute lymphoblastic leukemia. J Clin Oncol. 2020;38(28):3282-3293. doi:10.1200/JCO.20.00256