Abstract
Background & Rationale:Philadelphia-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL) accounts for ~20–30% of adult ALL. Contemporary frontline regimens combine a BCR-ABL1 tyrosine-kinase inhibitor (TKI) with the CD19-directed bispecific T-cell engager blinatumomab. Patients with end-stage renal disease (ESRD) are routinely excluded from clinical trials, and there are no prospective data guiding the use of TKIs or immunotherapy in dialysis-dependent Ph+ ALL. Dasatinib is primarily hepatically cleared but exhibits highly variable exposures in ESRD, having been reported to reach supratherapeutic troughs and cardiotoxicity. Blinatumomab (54 kDa) is minimally removed by standard high-flux dialysis filters, yet only anecdotal safety data exist. To date, the literature is limited to isolated reports of reduced-dose imatinib or dasatinib monotherapy in dialysis patients. Here we describe successful use of full-dose dasatinib combined with continuous-infusion blinatumomab in a patient on thrice-weekly hemodialysis, resulting in a durable MRD-negative remission.
Case Description:A 63-year-old man with ESRD on hemodialysis (HD) presented with abdominal pain and was found to have circulating blasts. Bone-marrow aspirate confirmed Ph+ B-ALL with 77% blasts, BCR-ABL1 p190 fusion, monosomy 7, and IKZF1 deletion. Initial blood counts were notable only for baseline anemia.
Treatment consisted of dasatinib 100 mg once daily plus standard dose blinatumomab (step-up 9 µg → 28 µg/day) with intrathecal prophylaxis. HD was scheduled immediately prior to each blinatumomab bag change to minimize drug loss and manage fluid shifts. The first cycle was complicated only by grade 1 cytokine-release syndrome; no ICANS occurred. Other toxicities included episodic pancytopenia, mucositis, rash, pleural effusions and volume overload, all managed with supportive care and transient dose holds.
Results:After cycle 1 the patient achieved MRD-positive complete remission (BCR-ABL1/ABL1 ratio 0.019%, 3.6-log reduction). Following cycle 2, bone-marrow biopsy demonstrated MRD-negative complete remission with undetectable BCR-ABL1. Serial lumbar punctures remained negative. The molecular remission was sustained for 11 months until the patient died in continuous remission from dialysis-related sepsis considered unrelated to therapy. No dialysis-associated clearance of blinatumomab was clinically apparent, and no high grade cardiopulmonary toxicity attributable to dasatinib occurred.
Discussion:Few case reports have described administration of TKIs in dialysis-dependent Ph+ ALL, and none have combined a TKI with blinatumomab. Our case demonstrates that standard-dose dasatinib and blinatumomab can be delivered safely with careful HD scheduling, yielding a deep and durable molecular remission. Pharmacologic principles support this approach: dasatinib is ~96% protein-bound and predominantly fecally excreted, while blinatumomab's molecular weight exceeds the cutoff of conventional filters. Prospective PK studies and multi-institutional registries are warranted to optimize dosing and broaden access for this high-risk population.
