Highlights in acute lymphoblastic leukemia

In the selection of his key highlights related to acute lymphoblastic leukemia, Dr Jan Brijs (University Hospital Lille, Lille, France) focussed on the integration of immunotherapeutic agents such as blinatumomab or inotuzumab ozogamicin (Ino) in first line treatment regimens for patients with B-ALL. In addition, an study was presented evaluating the potential of asciminib in patients with Philadelphia chromosome positive (Ph+) B-ALL.

Blinatumomab is a well established treatment for patients with relapsed/refractory (R/R) B-ALL. More recently, studies have also demonstrated the potential of this agent to  eradicate minimal residual disease (MRD) in B-ALL patients with residual MRD-positivity in first or second remission. In addition, phase II studies such as HOVON 146 and  a phase II study from the MD Anderson cancer center have also demonstrated a benefit when integrating blinatumomab in the first line treatment of MRD-negative B-ALL patients. The latter was recently confirmed in the randomised phase III E1910 study. In this trial, the addition of blinatumomab to consolidation chemotherapy significantly improved the overall survival (OS) of adult B-ALL patients in MRD-negative remission after induction and intensification chemotherapy.¹ Further subgroup analyses of this trial have suggested that the use of blinatumomab in this setting did not improve outcomes in patients above the age of 55 years. Furthermore, subgroup data indicate that the benefit of blinatumomab is particularly pronounced in patients with adverse risk features. Finally, the E1910 investigators looked into the role of an alloSCT as consolidation therapy. Interestingly, alloSCT did not differ between patients with or without blinatumomab in consolidation. In a multivariate analysis of all MRD-negative patients in E1910, only the receipt of blinatumomab but not alloSCT proved to be associated with an improved OS.¹ Based on the results of E1910 and earlier studies, Dr Brijs concludes that blinatumomab should now be considered standard of care in the 1st line treatment of both MRD-positive and -negative patients after induction chemotherapy. However, several questions remain to be answered. This includes the optimal number of blinatumomab cycles, the potential of blinatumomab to replace chemotherapy, the potential to sequence blinatumomab with CAR-T therapy and the place of alloSCT in the treatment landscape of B-ALL patients.

A second immunotherapeutic agent that has become an established part of the treatment armamentarium for R/R ALL consists of the antibody-drug conjugate inotuzumab ozogamicin (ino). More recently, this agent was also evaluated as a more tolerable alternative to high intensity induction therapy for elderly B-ALL patients. For example, induction therapy with ino was investigated in the INITIAL-1 trial. In this trial 45 older patients (median age: 64 years) received two to three cycles of dexamethasone with ino, followed by chemotherapy. All patients responded, and 71% of responders achieved MRD negativity. After a median follow-up of 2.7 years, the 3-year event-free survival (EFS) and OS rates were 55% and 73%, respectively.² Similarly, the EWALL-INO trial evaluated low-intensity chemotherapy with ino as frontline therapy among 131 older patients (median age, 68 years). The ORR and MRD negativity rates in this trial were reported at 90% and 80%, respectively with a the 2-year OS rate of 73%.³ As such, these results show improved outcomes with the integration of ino into the frontline treatment of older patients with Ph-negative B-ALL.

In the final part of the video, Dr Brijs turns the attention to patients with Ph+ B-ALL. While these patients generally have a better prognosis than Ph- patients, there continues to be a need for better treatment options. In this respect, several studies are evaluating the potential of asciminib, an allosteric inhibitor of BCR::ABL1 that targets the ABL1 myristoyl pocket. During EHA 2025, results were presented of the first study evaluating this agent as monotherapy in the treatment of R/R Ph+ B-ALL. The study included 28 adults with Ph+ ALL who were R/R to ≥1 prior TKI or intolerant of TKIs. Patients received asciminib at a starting dose of 40 mg BID, and an adaptive Bayesian logistic regression model guided dose escalation to 280 mg BID.⁴ The median age of patients in the study was 60 years and patients were heavily pretreated (89.3% ≥2 prior TKIs, 53.6% prior ponatinib, 46.4% post transplant relapse). The median duration of exposure was short at only 9.5 weeks, with 8/28 and 4/28 pts receiving ASC for ≥24 weeks and ≥144 weeks, respectively. The treatment was generally well tolerated and asciminib showed promising antileukemic activity, with a couple of patients (those with longer drug exposure) experiencing long-term disease control. As such, these findings demonstrate the feasibility to use asciminib in this setting and form the basis for further exploration of asciminib in Ph+ B-ALL, most likely in combination with other TKIs.