Early intensification with postinduction myeloid-type chemotherapy may not improve outcomes in infants younger than 1 year with acute lymphoblastic leukemia (ALL) compared with lymphoid-type chemotherapy, according to results from a study published in the Journal of Clinical Oncology.
Lysine methyltransferase 2A (KMT2A) gene rearrangements and coexpression of myeloid markers typically characterize infant ALL and are associated with worse prognosis. The KMT2A gene codes a transcriptional coactivator involved in hematopoiesis.
The Interfant-06 trial (ClinicalTrials.gov Identifier: NCT00550992) comprised 18 national and international study groups and assessed whether myeloid-style consolidation chemotherapy improves outcomes compared with lymphoid-style chemotherapy, what role stem cell transplantation (SCT) plays in these patients, and what additional factors were independently prognostic.
Researchers classified 651 patients as low-risk (germline KMT2A), high-risk (KMT2A-rearranged, 6 months or older, and with white blood cell count ≥ 300 x 109/L or a poor prednisone response), or medium-risk (all other cases of KMT2A rearrangements).
Patients in the medium- and high-risk groups were randomly assigned to receive lymphoid course chemotherapy (161 patients) or experimental treatment with myeloid chemotherapy (169 patients).
The 6-year probability for disease-free survival was similar between treatment arms, at 39.3% in the experimental myeloid arm compared with 36.8% in the controlled lymphoid arm (P =.47). Overall survival (OS) at 6 years was not significantly different between patients receiving myeloid- and lymphoid-type chemotherapy (54.4% vs 47.1%; P =.027).
The 6-year event-free survival (EFS) for the overall study population was 46.1%, and the 6-year OS was 58.2%. Patients in the West European and North American study groups experienced 6-year EFS of 49.4% (P =.0018) and 6-year OS of 62.1% (P <.001), a 10% to 12% improvement compared with patients in other countries. These regional differences were “mainly because of fewer toxic deaths, illustrating how regional handling of this protocol influences outcome,” according to the authors.
In high-risk patients with the intention of undergoing SCT, 6-year EFS was 20.9%. Because many of these infants experienced early events, only 46% of them actually underwent SCT.
Independent prognostic factors for inferior EFS included KMT2A rearrangement, younger age at diagnosis, WBC count of 300 x 109/L or more, and poor response to prednisone.
The authors noted that future studies will assess the use of epigenetic drugs and immunotherapy with the lymphoid-type chemotherapy backbone.
1. Pieters R, De Lorenzo P, Ancliffe P, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the Interfant-06 protocol: results from an international phase III randomized study [published online July 8, 2019]. J Clin Oncol. doi:10.1200/JCO.19.00261