Full-Course Immunotherapy Consolidation for Unfit or Fit B-ALL Who Decline Chemotherapy

Prior treatment

• Concurrent other active malignancies or malignancies requiring treatment.
• Prior exposure to CD19- or CD22-targeted therapies (including but not limited to CD19-directed CD3 T-cell engager, inotuzumab ozogamicin, CD19 or/and CD22 CAR-T).
• Use of immunosuppressive agents within 2 weeks prior to signing informed consent, or planned long-term immunosuppressive therapy after enrollment.
• Severe chronic liver disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis \[HBsAb-positive, HCVAb-positive\]).
  • 1、Patients with occult or prior HBV infection (defined as HBcAb-positive, HBsAg-negative) are eligible only if HBV DNA PCR is negative, and require monthly HBV DNA monitoring with prophylactic antiviral therapy.
  • 2、HCV antibody-positive patients are eligible only if HCV RNA PCR is negative. 3、History of confirmed severe or persistent veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).
  • (7) Bacterial, fungal, viral, mycoplasma, or other infections that are uncontrolled as judged by the investigator; HIV, syphilis, or SARS-CoV-2 infection.
  • (8) Past or current CNS disorders, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease.
  • (9) Primary immunodeficiency or active autoimmune disease. (10) History of severe immediate hypersensitivity to any study drugs. (11) Receipt of live vaccine within 6 weeks prior to screening. (12) Psychiatric disorders or other conditions that may compromise compliance with study requirements, treatment, or monitoring.
  • (13) Pregnant or breastfeeding women, or fertile patients unwilling to use contraception.
  • (14) Any other condition deemed unsuitable for study participation by the investigator.

Other illness

• Presence of central nervous system (CNS) or other extramedullary disease.
• Active cardiac disease (NYHA Class ≥3 as assessed by medical history and physical examination).

• Newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients aged ≥60 years, as per NCCN guidelines.
• Newly diagnosed B-ALL patients aged ≥15 to \<60 years who are unfit for intensive chemotherapy (Unfit), as per NCCN guidelines, meeting at least one of the following criteria:
  • 1、ECOG score ≥2 2、Severe cardiac comorbidities (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction ≤50%, unstable angina) 3、Severe pulmonary comorbidities (e.g., DLCO ≤65%, FEV1 ≤65%) 4、Severe renal comorbidities (e.g., serum creatinine \>2×upper limit of normal (ULN), creatinine clearance \<45 mL/min by any formula) 5、Severe hepatic comorbidities (e.g., total bilirubin \>1.5×ULN, AST/ALT/ALP \>3×ULN) 6、Active infection refractory to antimicrobial therapy 7、Documented cognitive impairment 8、Other comorbidities contraindicating intensive chemotherapy (3) Newly diagnosed B-ALL patients aged ≥15 to \<60 years with good performance status and adequate organ function who decline intensive chemotherapy for subjective reasons (Fit-Declined), as per NCCN guidelines (e.g., fear of toxicity, financial/social/psychological factors, preference for quality of life).
  • (4) Patients aged ≥15 years with relapsed/refractory B-ALL or MRD positivity after prior chemotherapy (5) All patients must meet the following organ function requirements:
• Left ventricular ejection fraction (LVEF) ≥40% by echocardiogram
• Creatinine clearance ≥30 mL/min (by any formula)
• ALT and AST ≤3×ULN, total bilirubin ≤2×ULN (unless attributed to leukemia)
• ≤Grade 1 dyspnea and oxygen saturation \>91% without supplemental oxygen (6) Ability to understand and voluntarily sign the informed consent form. (7) Life expectancy ≥3 months.