Comparison of Acute Kidney Injury in Patients with Relapsed or Refractory Multiple Myeloma Following CAR T-Cell and Bispecific Antibody Therapies
Authors: Nishimura Noriko , Mailankody Sham , Nemirovsky David , Derkach Andriy , Costa Bruno Almeida , Farzana Tasmin , Shaikh Aisha , Latcha Sheron , Gutgarts Victoria , Jurgens Eric M , Firestone Ross S , Nath Karthik , Chung David J. , Landau Heather J. , Scordo Michael , Shah Gunjan L. , Shouval Roni , Hashmi Hamza , Hassoun Hani , Maclachlan Kylee H , Hultcrantz Malin , Korde Neha , Lesokhin Alexander M. , Shah Urvi A. , Tan Carlyn Rose , Giralt Sergio A. , Usmani Saad Z. , Rajeeve Sridevi 
Published: December 2024

Introduction/Background: Chimeric antigen receptor (CAR)-T cell and bispecific antibody (BsAb) therapies demonstrated high response rates in relapsed/refractory multiple myeloma (RRMM), yet patients often experience significant toxicities. Data on the incidence, risk factors, and outcomes of acute kidney injury (AKI) following CAR T cell and BsAb therapies in RRMM are scarce.

Methods: This retrospective study included 205 patients with RRMM who received either first commercial CAR-T cell therapy (n=112) or commercial BsAb therapy (n=93) at our institution between February 2021 and March 2024. Acute kidney injury (AKI) was defined using KDIGO criteria as follows: stage 1 (creatinine rise ≥0.3 mg/dl or 1.5× baseline), stage 2 (2× baseline), and stage 3 (3× baseline). Incidence of AKI occurring up to 90 days post-CAR-T or BsAb therapy was assessed using cumulative incidence following either therapy or death as a competing risk. Univariable cause-specific Cox regression models were constructed to evaluate association with event-free survival (EFS): defined as the time from infusion of BsAb or CAR-T to the date of disease progression, subsequent treatment, or death from any cause: and overall survival (OS). Chronic Kidney Disease (CKD) was defined as eGFR of &lt;60 ml/min/1.73m2 over 3 months using the CKD Epidemiology Collaboration (CKD-EPI) formula.

Results: The prevalence of chronic kidney disease (CKD) at baseline was similar in the BsAB and CAR-T groups, 17% vs. 21%, respectively with two patients on maintenance hemodialysis in each group. Compared to the CAR-T cohort, patients treated with BsAb were older (median age: 71 years vs. 67 years) and had a higher proportion with creatinine clearance (CrCl) &lt;60mL/min (44% vs. 26%) at baseline, a higher proportion of albumin &lt;3.5g/dL (47% vs. 21%), a lower proportion of M-spike &lt; 1.5g/dL (73% vs. 97%), and more high-risk cytogenetics (54% vs. 37%). Among patients treated with CAR-T, fludarabine was omitted in 12% due to shortages and reduced in 34% due to CrCl.

In the entire cohort at the day 30 timepoint, highest stage I, II & III AKI were seen in 8.3%, 2.1%, 0.53%, respectively. The cumulative incidence of AKI within 90 days was 16% for any stage. There was no significant difference in the incidence of any-stage AKI at 90 days between CAR-T or BsAb treated patients (17% vs. 14%, p=0.5). All patients recovered from post infusion AKI, except for 2 patients treated with BsAb who died of pneumonia within a month without AKI recovery. The median time to recovery from AKI was 3 days (IQR 1-7) in BsAb group and 2 days (IQR (1- 4) in CAR-T group. In univariable Cox regression models, baseline albumin &lt;3.5g/dL (HR: 2.24, 95% CI: 1.10-4.60, p=0.029), M-spike ≥1.5g/dL (HR: 4.03, 95% CI: 1.93-8.40, p&lt;0.001), and ICANS (HR: 2.85, 95% CI: 1.21-6.70, p=0.029), were associated with shorter time-to-AKI, while treatment modality (BsAb vs CAR-T), baseline CKD, and fludarabine use were not. In multivariable analysis, only M-spike ≥1.5g/dL remained significant (HR: 4.11, 95% CI: 1.49-11.3, p=0.009).

At a median follow-up of 8.3 months following BsAb and 10 months following CAR-T, AKI was associated with inferior OS by univariable analysis in both BiTE (HR 3.37; 95% CI, 1.68-8.30, p=0.003) and CAR-T (HR 3.49; 95% CI, 1.22-9.98, p=0.035) groups. Patients who developed AKI had significantly lower OS (HR 2.67; 95% CI, 1.25-5.69, p=0.011) in the entire cohort in multivariable analysis, while stratifying by treatment and adjusting for age, cytogenetics, prior lines of therapy, and M-spike. There was no significant association between AKI and EFS. MM and infections are the most frequent primary cause of death.

Conclusion: Our study found that in patients with RRMM, higher tumor burden, as indicated by high M-spike, increases the risk of AKI following BsAb and CAR T-cell therapies. The overall incidence of AKI was low, and AKI was reversible in most patients. AKI was associated with inferior survival highlighting that AKI, even if transient, may be a poor prognostic marker. Larger studies can help corroborate these findings which suggest that pts with pre-existing CKD can undergo BsAbs and CAR-T therapy without worsening of their renal function and that AKI in the immediate post therapy setting is usually transient and reversible.