Assessment of Central Nervous System Responses in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Receiving Brexucabtagene Autoleucel As an FDA-Approved Standard of Care

Transplantation and Cellular Therapy(2024)

Cited 0|Views21
No score
The central nervous system (CNS) respresents a common site of extramedullary disease relapse in acute lymphoblastic leukmeia (ALL). CNS relapses contribute to adverse outcomes, and frequently exclude patients from participating in clinical trials. Current approved novel salvage therapies (bliantumomab and inotuzumab) have limited activity in B-ALL with CNS relapse. Brexucabtagene autoleucel (brexu-cel) was the first FDA-approved CAR T-cell product for adult patients with relapsed/refractory (r/r) B-ALL based on the ZUMA-3 study, which excluded patients with clincally evident CNS involvement. The safety and efficacy of using brexu-cel in these patients is yet to be established.Methods: Data from the Real World Outcomes Collaborative for CAR T in ALL (ROCCA), a retrospective, consortium of more than 25 U.S. institutions, were used to study adult patients with r/r B-ALL who received brexu-cel as standard of care therapy. The patient population for this analysis includes adults with active CNS disease (CNS 2 or CNS 3) at apheresis. CNS disease was classified into CNS 1 (no identifiable CNS disease), CNS 2 (detectable blasts in CSF with < 5 WBC/uL), and CNS 3 (detectable blasts with >5 WBC/uL and/or clinical signs). ASTCT consensus criteria were used for CRS and ICANS.Results: Of 152 patients infused, 28 (18%) had CNS 2 (n =13) or CNS 3 (n = 15) status at the time of pre-apheresis disease assessment. Patients had a median age of 48 years (range, 24-76), and 57% were males. Twelve of 28 patients had Ph-neg B-ALL. At first diagnosis, 20 (71.4%) patients had CNS 1 disease. Additionally, 13 (46.4%) had active systemic disease in addition to their CNS disease while 15 patients were in morphologic remission, 8/15 being MRD negative. Eight patients received IT chemotherapy as part of their bridging therapy. Only 7/28 patients underwent follow up CNS evaluation after bridging therapy prior to CAR T infusion, and all of them experienced disease clearance. Of 19 evaluable patients who did not receive IT bridging, 17 (89.5%) cleared CNS disease (CNS 1) after brexu-cel. Two patients had persistent CNS disease: one with CNS 2 and one with CNS 3 disease. ICANS occurred in 23/28 (82.1%) patients; however, only one patient (3.6%) experienced grade 3-4 ICANS. This compared favborably to the overall cohort in which 9% experienced grade 3-4 ICANS.Conclusion: This is the first study examining CNS responses to brexu-cel in adults with B-ALL entering CAR T with active CNS involvement. We uncovered high rates of CNS ALL clearance with a single infusion of brexu-cel. While most patients experienced low grade ICANS, severe ICANS was rare and less common than among the general brexu-cel treated population.
Translated text
AI Read Science
Must-Reading Tree
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined