Page 74 - Haematologica Vol. 110 - January 2025

ARTICLE - Real-life study on 421 adult Ph-neg ALL treated with LAL1913 program D. Lazzarotto et al.
LAL1913 clinical trial. Moreover, our analysis confirms the important role of HSCT in patients with high-risk factors or MRD positivity. Therefore, outside of clinical trials, efforts should be made to examine the disease characteristics in detail, keeping up with recently identified molecular subgroups, and to strictly monitor MRD at the appropriate timepoints to better identify patients with risk factors for early HSCT referral.9,10
A limitation of our study is that, for the majority of the pa- tients, the Ph- like signature was not available; this should be more widely tested in standard clinical practice.25-28 Furthermore, the widespread use of immunotherapy in patients with persisting pre-transplant MRD could improve transplant outcome. We are waiting for the results of the studies testing these approaches in patients with baseline high-risk features29 or in all cases, including MRD-negative patients, where blinatumomab also appears to be effective.30 The tolerability of pegaspargase in the real-life setting re- mains an important concern, given the role of this drug as a cornerstone in the therapy regimen, and, indeed, our study is limited by the lack of a precise correlation analysis between pegaspargase dosage and response. Future studies are need- ed to personalize drug dosage for each patient according to tolerance, while remaining within the range of efficacy.8,20,22,31,32 The widespread availability of asparaginase activity monitoring could help optimize dose calculation.33
A detailed analysis of infectious complications was beyond the scope of this study and will be detailed in a subsequent report. However, this remains an important issue to address, as infections are an important cause of morbidity and mortal- ity, and efforts should be made to standardize anti-infectious
References
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prophylaxis, especially on the anti-mycotic front.24,34
Finally, elderly patients still show inferior outcomes com- pared to younger patients, even observing a median OS of 45 months. Future studies should aim at identifying the optimal age cut-off to define the “elderly”, and to de- sign better and tailored induction therapies incorporating front-line immunotherapy to reduce toxicity and improve outcome.35-37
Disclosures
No conflicts of interest to disclose.
Contributions
AC designed the study (of which she is Principal Investiga- tor), and wrote and revised the paper. DL collected data, performed the analysis, and wrote the paper. RF, CP, MC and SC collected data and helped revise the paper. All other authors collected data and approved the final manuscript.
Acknowledgments
We would like to thank all the members of the Campus ALL-Italy network.
Funding
This work was partly supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), 5x1000 Metastases Special Program, N. 21198, Milan, Italy (to RF).
Data-sharing statement
Data regarding this research cannot be shared openly due to patient privacy concerns.
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treatment regimens for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a review. JAMA Oncol. 2018;4(5):725-734.
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