Dr Patel on the Feasibility of Outpatient Treatment in Ph+ ALL

Anand Patel, MD, University of Chicago, discusses a phase 2 study that investigated the efficacy and safety of a TKI and inotuzumab ozogamicin (InO; Besponsa)-based therapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The primary goal was to achieve a high rate of minimal residual disease (MR3+) while reducing intense chemotherapy and prolonged inpatient antibody treatment, which are often associated with other regimens like TKI plus blinatumomab (Blincyto).

The study enrolled 21 patients (pts) with a median age of 60. Eligibility required newly diagnosed Ph+ ALL, age ≥18, ECOG ≤2, and CD22+ on ≥20% of blasts. Treatment evolved from schema 1 to schema 2 after 2 patients on cchema 1 developed veno-occlusive disease (VOD) outside the initial dose-limiting toxicity (DLT) window. Schema 2 included dasatinib (Sprycel) and dexamethasone in course 1 (C1), InO in C2, followed by TKI plus POMP for C3, and so on. TKI was switched from dasatinib to ponatinib (Iclusig) if MR4 was not achieved by the end of course 2 (EOC2).

The therapy demonstrated high response rates:

• The MR3+ rate (MR3 or MR4, indicating a BCR::ABL1 qRT-PCR of <0.1% or <0.01%) was 81% after 2 courses across all patients.
• The MR4 rate was 62% at EOC2 and 90% at the end of course 3 (EOC3).
• The NGS MRD negative (MRD–) rate was 62% by EOC2 and 90% by EOC3. By EOC3, 100% of patients achieved either MR4 or NGS MRD- disease.
• For the 14 patients treated on schema 2, no VOD or DLTs occurred.
• The estimated 2-year overall survival was 79%.

The TKI plus InO-based therapy for newly diagnosed Ph+ ALL successfully met the efficacy end point, achieving an 81% MR3+ rate within 2 courses with limited cycles of InO. The modified schema 2 eliminated VOD complications, supporting further development of this induction approach.

REFERENCE

Patel A, Duvall A, Saygin C, et al. Primary efficacy analysis of phase II study investigating tyrosine kinase inhibitor (TKI) and inotuzumab ozogamicin-based therapy for newly diagnosed Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Presented at: 67th ASH Annual Meeting; December 6–9, 2025; Orlando, Florida. Abstract 441.