ABC Regimen: Combination of 3rd Generation TKI Olverembatinib, Blinatumomab and Chidamide for Older New Diagnosed Ph-Positive ALL Patients

Background

Tyrosine kinase inhibitors (TKIs) have improved the long-term outcomes of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), but resistance to TKIs remains a challenge. Previous reports showed that 3rd generation TKI ponatinib, combined with chemotherapy, result in modest rates of complete molecular response (CMR) of 75% in three months. Our recent study, a frontline combination of Olverembatinib and PDT-ALL-2016 regime in Ph+ALL, had shown a promising outcome, achieving a complete molecular response (CMR) rate of 84.6% at day 90. Furthermore, the combination of TKI and blinatumomab (BITE) as chemotherapy-free treatment approach had been demonstrated safety and effective, however, the long-time survival is unsatisfactory, especially for those who harbored IKZF1 deletion. Our previous work showed that chidamide, a histone deacetylase inhibitor, can upregulate the expression of IKZF1 for ALL patients who had IKZF1 deletion. Hence we designed an ABC regimen (NCT06220487) that combined 3rd Generation TKI Olverembatinib, Blinatumomab and Chidamide as a chemo-free regimen for new diagnosed Ph-positive ALL.

Methods

From June 2022 to Nov 2023, 9 patients with new diagnosed Ph+ ALL treated with ABC regimen were enrolled, The detail of ABC regimen was showed in Figure 1 (Induction×1: corticosteroid prephase: prednisone, 1-14 day; olverembatinib: 40mg, 8-42 day, Qod; blinatumomab: 28ug, 15-28 day; chidamide: 10mg, 28-41 day, Qod; and consolidation×4：olverembatinib: 40mg, 1-42 day, Qod; blinatumomab: 28ug, 1-24 day; chidamide: 10mg, 15-41 day, Qod). Complete Molecular Remission (CMR) was defined as absence of a detectable BCR-ABL1 transcript quantitative RT-PCR analysis at a sensitivity of 0.01%, and continuously monitor in day30, day60 and day90 after receiving olverembatinib.

Results

A total of 9 patients were enrolled in this study. The median age was 61 (50-73) years old, 6 (66.67%) patients had ≥2 comorbid diseases. The characteristics were list in Table 1. With a median follow-up of 14 months, all patients achieved complete remission (CR) after induction. Four patients (44.4%) achieved CMR after induction, 7 patients (77.7%) achieved CMR at 2 months and 8 patients (88.8%) achieved CMR at 3 months. No patients died or relapse within duration of follow-up, the 1.5 year OS and EFS was 100%.

Adverse events were observed in 4 (44.5%) patients, one patient developed septic shock during treatment. One patient experienced grade 2 cytokine release syndrome (CRS) and pneumocystis jiroveci pneumonia. One patient developed herpes zoster. One patient developed transient ischemic attack.

Conclusion

This study showed the good efficacy and safety of ABC regimen for Ph-positive ALL. All the 9 patients were elderly, most of them combined with more than 2 comorbid diseases, ABC regimen showed good safety for them. Moreover, a notable rate of survival and CMR were observed, the 3 month CMR was 88.8%, the 1.5 year OS and EFS were 100%, no patients relapsed or died, which holds promise for improved long-term survival. (This work was supported by National Natural Science Foundation of China [81770170, 81970147, 82170163], Clinical Trial Funding of Nanfang Hospital, Southern Medical University [2023CR009, LC2016ZD009, 2019CR012])

No relevant conflicts of interest to declare.