Dr Patel on MRD Responses With Inotuzumab Ozogamicin Plus Dasatinib in Ph+ ALL

"When looking at the entire cohort of 21 patients treated on the study, we found that within 3 courses of therapy, 90% of patients achieved an MR4 or better.”

Anand Patel, MD, an assistant professor of medicine and medical director of Inpatient Leukemia Service at the University of Chicago Medicine, discusses primary findings from a phase 2 study (NCT04747912) evaluating the efficacy and safety of the TKI dasatinib (Sprycel) and inotuzumab ozogamicin (InO; Besponsa)–based therapy for patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph-positive ALL).

Findings presented at the 2025 ASH Annual Meeting and Exposition confirmed that dasatinib plus inotuzumab ozogamicin–based induction therapy produced high rates of MR3 or greater after 2 courses of therapy, Patel reported. Overall, by the end of course 3 (EOC3), 100% of patients in the full cohort (n = 21) achieved either MR4 or minimal residual disease (MRD)–negative disease at a sensitivity of 10-6 by next-generation sequencing; 90% of these responses were MR4, 5% were MR3, and 5% were complete response (CR). The MRD-negativity rate was 90% at EOC3. Notably, 2 patients had MRD-negative disease per next-generation sequencing despite not achieving MR4 at this time point.

Of note, the trial utilized a modified schema (Schema 2) that successfully eliminated the complication of veno-occlusive disease (VOD), supporting the further development of this induction approach. For the 14 patients treated on Schema 2, no VOD or dose-limiting toxicities (DLTs) occurred. Moreover, by the end of course 2, the MR4 rate in this patient population was 57%, the MR3 response was 14%, and the CR rate was 29%, indicating deep molecular response. Best responses at EOC3 included MR4 (93%) and CR (7%).

At a median follow-up of 2.1 years, the 2-year overall survival rate in the 21-patient cohort was 80% (95% CI, 64%-100%), Patel noted. Crucially, only 1 systemic relapse of disease occurred, and no patients had relapses in their central nervous system, he added. Furthermore, no patients treated on the study received allogeneic stem cell transplant, Patel concluded.