It is a new and exciting time for acute lymphoblastic leukemia (ALL). While nearly 50 years ago, only one in nine children with ALL survived with chemotherapy, nowadays nearly 90% of children have a chance of long-term survival. Adults with ALL, as well as the special category of adolescents and young adult (AYA) patients, are catching up with the new developments seen in children, but still their prognosis is much worse. A plethora of factors are regarded as responsible for the differences in treatment response, such as age, ethnicity, disease biology, treatment regimens and toxicities, drug tolerance and resistance, minimal residual disease evaluation, hematopoietic stem cell transplantation timing and socio-economic factors. Taking these factors into account, bringing pediatric-like protocols to adult patient management and incorporating new agents into frontline treatment could be the key to improve the survival rates in adults and AYA.

Introduction. The advent of Bruton’s tyrosine kinase (BTK) inhibitors brought about a paradigm shift in the management of chronic lymphocytic leukemia (CLL), by offering a well-tolerated chemotherapy-free approach. Here, we share the experience with ibrutinib of a major Romanian regional cancer center. Methods. We screened patients treated for CLL in our center over 6 years (2017- 2022) and included those who were treated with ibrutinib either in the first line of therapy or in subsequent lines. Results. We enrolled 61 patients, 40 with treatment-naïve (TN) CLL and 21 with relapsed/refractory (R/R) CLL, with a median age at treatment initiation of 65 years. Concerning the prognostic-predictive workup, IgHV mutational status was available for 78.7% of the patients, TP53 sequencing for 82%, assessment of 17p deletion for 82%, and CD38 marker analysis was performed for 70.5%. With a median follow-up period of 55 months, the overall response rate (ORR) was 90.2%, with a median progression-free survival (PFS) of 33 months and a median overall survival (OS) that has not been reached. In our cohort, albeit non-significant statistically, patients with TP53 mutation had a shorter OS and those with mutated IgHV, a shorter PFS. Rai 3-4 and Binet C stages at diagnosis were associated with a shorter PFS, but not OS. In our cohort, the correlation between survival and high Cumulative Illness Rating Scale (CIRS) index was not statistically significant. Ibrutinib was generally well tolerated in our cohort, as only 14.8% of our patients discontinued treatment due to adverse effects. Conclusion. Our study suggests that ibrutinib is a valid therapeutic option for TN or R/R CLL patients, with a high ORR and a good safety profile.