Chemotherapy-Free Achievement of Minimal Residual Disease in a Jehovah’s Witness Patient With Ph-Negative B-ALL

BACKGROUND Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL) is usually treated with intensive chemotherapy, presenting challenges for Jehovah's Witness patients who refuse blood products due to religious beliefs. These regimens often lead to severe cytopenias that require transfusion support. New targeted therapies (eg, inotuzumab ozogamicin and blinatumomab) have become effective options with lower toxicity, particularly for older or frail patients; these benefits may extend to the Jehovah's Witness population. CASE REPORT A 44-year-old Jehovah's Witness man was diagnosed with Ph-negative B-ALL. His comorbidities included hypertension, atrial fibrillation, and a newly identified reduced ejection fraction of 30% to 35%, which precluded the use of anthracyclines. Due to his refusal of blood products and cardiac limitations, he was treated with a chemotherapy-free regimen consisting of inotuzumab induction followed by blinatumomab consolidation. Supportive care included epoetin alfa, romiplostim, iron, and vitamin supplementation. The patient tolerated induction well, with minimal cytopenias and no serious adverse effects. After 2 cycles of inotuzumab, he achieved complete morphologic remission and minimal residual disease (MRD) negativity according to ClonoSEQ. He is currently receiving consolidation with blinatumomab. CONCLUSIONS This is the first known reported case that demonstrates the feasibility and effectiveness of a chemotherapy-free induction strategy using inotuzumab and blinatumomab for frontline treatment of Ph-negative B-ALL in Jehovah's Witness patients. It shows that MRD negativity can be safely achieved without cytotoxic chemotherapy or transfusion support and supports the use of the ALLIANCE A041703 trial regimen as a treatment model for this unique and underserved patient group.