Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia Lymphoma (TACL) Study
Mené sur 22 patients d'âge inférieur à 21 ans et atteints d'une leucémie lymphoblastique aiguë récidivante, cet essai de phase II évalue le bortezomib en combinaison avec une chimiothérapie à base de vincristine, dexaméthasone, asparaginase pégylée et doxorubicine
Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in 2nd and subsequent relapse. The TACL phase I study, T2005-003 showed that combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase and doxorubicin has acceptable toxicity. The TACL consortium conducted the phase II expansion of this combination in relapsed ALL patients who failed 2-3 prior regimens. Twenty-two patients with relapsed ALL were treated with bortezomib combined with this regimen: ages were 1 - 21 years, with B-precursor ALL (20 patients) and T-cell ALL (2 patients). Grade 3 peripheral neuropathy developed in 2 (9%) patients. After 3 patients died from bacterial infections treatment with vancomycin, levofloxacin and voriconazole prophylaxis resulted in no further infectious mortality in the last 6 patients. Fourteen patients achieved complete remission (CR) and 2 CRp for an overall 73% response rate, meeting predefined criteria allowing for early closure. B-precursor patients faired best with 16/20 (80%) CR + CRp, whereas the 2 T-cell ALL patients did not respond. Thus this combination of bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic antibiotics may be useful in reducing mortality. Bortezomib merits further evaluation in combination therapy in pediatric B-precursor ALL. This study was registered at www.ClinicalTrials.gov as NCT00440726.
Blood 2012