medwireNews: First-line treatment with dasatinib is effective and well tolerated in chronic myeloid leukaemia (CML) patients aged over 65 years, shows an Italian clinical practice study.
The researchers believe that the second-generation tyrosine kinase inhibitor “could play a major role in the frontline treatment” of this patient population, the majority of whom have multiple comorbidities.
They identified a “real-life” cohort of 65 patients older than 65 years who received first-line dasatinib for chronic phase CML at 26 Italian centres between 2012 and 2015. More than half (60.1%) of the participants had one or two concomitant conditions requiring treatment, while nearly a third (30.7%) had at least three comorbidities.
The majority (83.0%) initiated dasatinib therapy at a dose of 100 mg/day, with the remaining starting treatment at doses of 80 mg or 50 mg once a day, report Roberto Latagliata (“Sapienza” University of Rome, Italy) and co-investigators.
Haematological and nonhaematological adverse events of grade 3 or 4 occurred in 12.3% and 18.5% of study participants, respectively. Among the 10 (15.4%) patients who discontinued treatment as a result of toxicities, six did so due to pleural effusion, equating to 9.5% of patients overall.
Noting that no patient initiating dasatinib at a dose below 100 mg/day discontinued therapy due to side effects, the team suggests that “[i]n the future, […] an individualized approach, consisting of a reduced starting dose with progressive modifications based on response and toxicity, could be useful at least in some patient[s] older than 65 years with comorbidities.”
Dasatinib, given for a median of 17 months, induced a complete cytogenetic response in 92.3% of patients, while 76.9% achieved a major molecular response.
As reported in Neoplasia, the cumulative event-free survival rates at 12 and 24 months were 85.4% and 69.3%, respectively, and the corresponding rates for cumulative overall survival were 98.3% and 89.9%.
Latagliata et al say that their study provides information on first-line dasatinib in a group of patients generally excluded from clinical trials. For instance, newly diagnosed CML patients in Italy are a median age of around 60 years, but the median age of participants in the DASISION trial pitting dasatinib against imatinib was under 50 years. By contrast, the median age of the current cohort was 75.1 years.
The study authors are aware, however, that their cohort may also be subject to selection bias “as many physicians still consider [imatinib] therapy the best frontline drug for patients older than 65 years.”
They admit: “It is reasonable that, in our centers, low-risk or very frail patients older than 65 years probably did not receive [dasatinib] as frontline therapy and were not included in our real-life cohort.”
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016