Relapsed or Refractory ALL After Immunotherapy Did Not Achieve Complete Remission

Relapsed or primary refractory acute lymphoblastic leukemia (ALL) is a challenging clinical situation. Depending on subtype and protocol, 5–10% of patients have disease that never responds (primary refractory), and 30–60% will relapse after initial response. When second-line immunotherapy fails to achieve the remission needed to proceed, a further escalation is required.

Previous Line — What Didn't Work

Second-line immunotherapy with inotuzumab ozogamicin (for patients with high disease burden and CD22-positive ALL) or blinatumomab (for patients with lower disease burden and preserved T-cell function) was administered with the goal of achieving complete remission or complete remission with incomplete recovery (CR/CRi). This protocol is indicated when that remission goal was not reached — or when disease has recurred, including after stem cell transplantation (SCT).

Next-Line Approach

The protocol for this situation involves a targeted cellular immunotherapy strategy directed at a specific antigen expressed on leukemic blasts — particularly in the setting of more advanced or post-transplant relapsed disease. The full regimen, eligibility criteria, and sequencing are detailed in the structured protocol.

Full regimen, dosing, and algorithm available in the complete protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1182/blood.2023023568

Depending on protocol and subtype, 5% to 10% of patients will be primary refractory, and an additional 30% to 60% of patients will relapse.

CAR-T targeting the CD19 antigen have generated promising results in children and adults with R/R ALL.

CAR-T might be indicated to treat more advanced disease, particularly recurrence after SCT.

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