CAR T-Cell Therapy Plus Auto-HSCT Demonstrate Efficacy, Safety in Ph– B-ALL

Results from a phase 2 clinical trial (NCT05470777) show that the sandwich therapy of sequential CD22/CD19 chimeric antigen receptor (CAR) T-cell therapy with autologous hematopoietic stem cell transplantation (auto-HSCT) demonstrated significant efficacy and a favorable safety profile in patients with Philadelphia chromosome-negative (Ph-negative) B-cell acute lymphoblastic leukemia (B-ALL).¹

The study reported exceptional efficacy results at a median follow-up of 28 months (range, 10–50 months). With a median follow-up of 28 months, the 2-year overall survival (OS) rate was 97% (95% CI, 90%–100%) and the 2-year leukemia-free survival (LFS) rate was 72% (95% CI, 58%–90%). All 35 patients who completed the full treatment regimen survived. The strategy achieved deep and durable molecular remissions, with 80% of patients maintaining continuous measurable residual disease (MRD)-negative status.

The sandwich strategy induced progressively deeper remissions at each treatment stage. Post-chemotherapy, 92% of patients achieved complete remission (CR), with 54% achieving MRD-negativity by multiparameter flow cytometry (MFC). Post CAR-T1, 100% of patients achieved MFC-MRD-negative CR, and post CAR-T2, all patients remained MFC-MRD-negative CR, and 93% of evaluable patients achieved MRD-negativity by the more sensitive next-generation sequencing (NGS) method.

The remissions achieved were durable; 80% (n = 28/35) of patients maintained continuous MFC-MRD-negative CR after CAR-T2, and 72% (n = 20/27 evaluable patients) maintained continuous NGS-MRD-negative CR after CAR-T2.

Of the 35 patients who completed the sandwich strategy, 20% (n = 7) experienced relapse. The median time to relapse was 5 months. All relapses were CD19-positive. A high white blood cell count at initial diagnosis was identified as a potential risk factor for relapse. All patients who relapsed achieved CR again after salvage therapy with blinatumomab (n = 5) or chemotherapy (n = 2).

When compared to an external control group of patients who received allogeneic (allo)-HSCT, the sandwich strategy showed a significantly longer OS and a nonrelapse mortality (NRM) rate of 0%, versus 15% in the allo-HSCT group.

The strategy was effective regardless of genetic risk. There was no significant difference in OS or LFS between patients in the poor and standard-risk genetic groups. This suggests the sandwich strategy may overcome poor genetic risk factors.

An exploratory analysis comparing the 37 patients with an external control group of 52 patients who underwent allo-HSCT showed significant advantages in the sandwich strategy. OS was significantly longer in the sandwich strategy group (P =.021), and LFS was comparable between both groups (P =.576). The relapse rate was 24% in the sandwich strategy group vs 19% in the allo-HSCT group (P =.607).

These findings position the CD22/CD19 CAR T-cell and auto-HSCT sandwich strategy as a potent potential alternative to allo-HSCT, offering a path to allo-HSCT-free survival with reduced toxicity for patients with Ph-negative B-ALL.

Safety Profile

Notably, the treatment was well-tolerated, with no instances of severe (grade ≥3) cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) observed. Mild (grade 1–2) CRS occurred in 22% of patients after CAR-T1 and 34% of patients after CAR-T2.

All patients experienced expected grade 3-4 hematotoxicity. B-cell aplasia occurred in all patients. Four patients experienced infections (2 sepsis, 2 lung infections). No severe organ toxicity was reported.

Study Design and Methodology

This was a phase 2, open-label, single-center study with a total of 37 newly diagnosed adolescent, young adult, and adult patients (median age, 28 years) with Ph-negative B-ALL who were unable to undergo or declined all-HSCT. Of the total patients, 57% presented with high-risk genetic features. The primary end point was OS and the secondary end point was LFS.

Patients received standard induction and consolidation chemotherapy. This was followed by a first infusion of sequential CD22 and CD19 CAR T-cells. Patients then underwent auto-HSCT using a modified BuCy conditioning regimen. A second infusion of CD22 and CD19 CAR T-cells was administered 2 days after the autologous stem cell infusion.

“In conclusion, the CD22/CD19 CAR T-cells and auto-HSCT sandwich strategy is a promising approach for treating Ph-negative B-ALL in [adolescent, young adult] and adult patients, offering high efficacy with a favorable safety profile,” concluded study authors Qian et al. “Future studies with larger sample sizes and longer follow-up are warranted to further validate these findings and further explore allo-HSCT–free strategies.”

REFERENCE

1.Qian CS, Wang ZH, Li Z, et al. A phase 2 trial of a “sandwich” strategy: Sequential CD22/CD19 chimeric antigen receptor T-cells therapy combined with autologous hematopoietic stem cell transplantation in patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. Cancer. Published November 6, 2025. Accessed November 19, 2025. 2025;131(22):e70168-e70168. doi:10.1002/cncr.70168