Successful administration of chimeric antigen receptor (CAR) T-cell therapy in patients requiring hemodialysis

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B-cell malignancies. However, there is no data on the safety and efficacy of CAR T-cell therapy in patients with end stage renal disease (ESRD) requiring dialysis. In this report, we present two patients with DLBCL and ESRD who were successfully treated with different CAR T-cell products. Patient #1 is a 66 year-old woman with a history of HIV who was treated to complete response with axicabtagene ciloleucel with treatment complicated by grade 1 cytokine release syndrome (CRS) and grade 2 immune effector cell-associated neurolotoxicity syndrome (ICANS). Patient #2 is 52 year old woman whose ESRD was caused by ifosphamide toxicity and was treated to complete response with lisocabtagene maraleucel and did not experience either CRS or ICANS. Both patients received lymphodepletion chemotherapy with fludarabine and cyclophosphamide, which was dose-adjusted for ESRD with scheduled dialysis 12 h after each dose of lymphodepletion chemotherapy. Patients with DLBCL and ESRD can be safely administered both lymphodepletion chemotherapy and CAR T-cell therapy. Additionally, the fact that both patients achieved complete response to therapy suggests that CAR T-cell therapy should be strongly considered in patients with ESRD. Long-term follow up is needed to determine if therapy in this setting is of curative intent.

Chimeric antigen receptor T-cell therapy in a dialysis patient with lymphoma

“…A case series reported the successful treatment of two ESKD patients with CAR-T therapy for relapsed/refractory DLBCL. 8 Both patients received lymphodepletion chemotherapy with cyclophosphamide and dose-adjusted fludarabine, followed by HD 12 h post-treatment, similar to our patient. Both patients achieved an initial complete response, with one experiencing Grade 1 CRS and Grade 2 ICANS.…”

“…Cyclophosphamide was administered at a rate of 660 mg/24 h, and owing to her ESKD, the fludarabine was dose reduced to 20 mg/m 2 (from the recommended dose of 30 mg/m 2 ). 8 This dose reduction was derived from the limited existing literature in which fludarabine was used as a conditioning therapy in patients with ESKD undergoing stem cell transplantation. 9 She then received lisocabtagene maraleucel CAR-T therapy, a CD-19 directed modality which incorporates a 41-BB costimulatory domain.…”

Enabling CAR T‐cell therapies for HIV‐positive lymphoma patients – A call for action

“…Nine published case reports on CD19-targeted CAR T-cell therapy in patients with lymphoma and HIV were identified [31][32][33][34][35][36]. Three cases were excluded from the analysis because data were insufficient (Table 1) [34,35].…”

“…The optimal CD4 + /CD8 + CAR T-cell ratio has not been clarified, and the ratio differs according to the specific CAR T-cell product [23]. Notably, in all published cases of CAR T-cell treatment for r/r HIV-lymphomas, axicabtagene ciloleucel was used, a CAR T-cell product without a specific CD4 + /CD8 + ratio [26,[31][32][33][34][35][36].…”

Safe and successful CAR T-cell therapy targeting BCMA in a multiple myeloma patient requiring hemodialysis

“…Patients with severe renal insufficiency (RI) or receiving hemodialysis have typically been excluded from clinical trials. Thus, data for these MM patients are scarce, although now exist for patients with diffuse large B-cell lymphoma (DLBCL) [3,4].…”