Long-term complete remission and minimal side effects after CD19/CD22 CAR-T cell cocktail therapy in a living donor with DLBCL: A rare case report

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy is a breakthrough in cancer treatment that can induce durable remission in patients with hematological malignancies who have failed prior therapies. As the use of CAR-T cell therapy increases, treatment-related renal complications deserves careful attention, particularly in patients with a solitary kidney, in whom renal complications may further increase clinical risk. Here, we report the case of a living kidney donor who was diagnosed with diffuse large B-cell lymphoma (DLBCL). After CAR-T cell therapy, the patient developed only mild cytokine release syndrome (CRS), without signs of acute kidney injury or renal impairment, and subsequently achieved a favorable metabolic response approaching complete remission.

Background

Chimeric antigen receptor T-cell (CAR-T) therapy represents a major breakthrough in cancer treatment and has achieved durable remissions in patients with refractory hematological malignancies. However, its clinical application is frequently accompanied by adverse events, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis (HLH), and tumor lysis syndrome (TLS) ¹ . These complications may have substantial effects on renal function.

Renal injury following CAR-T cell therapy is multifactorial. CRS may induce vasodilation, capillary leak, and reduced cardiac output, leading to impaired renal perfusion and reduced glomerular filtration rate ² . Circulating cytokines may also contribute to cytokine-induced cardiomyopathy and direct inflammatory renal injury ³ . TLS results in the rapid release of intracellular metabolites, leading to metabolic disturbances and tubular injury^4,5. In addition, HLH-associated acute interstitial nephritis and thrombotic microangiopathy may further contribute to renal ischemia ⁶ .

With the increasing use of CAR-T cell therapy, accumulating evidence has demonstrated its association with renal complications. Acute kidney injury (AKI) is associated with increased mortality, particularly in severe cases ⁷ . A study demonstrated that patients with AKI had significantly shorter median progression-free survival (PFS) and overall survival (OS) ⁸ . Although the clinical impact of renal complications on long-term oncologic outcomes remains heterogeneous, renal dysfunction may complicate treatment and supportive care in selected patients.

Therefore, this case report aims to highlight the importance of careful renal monitoring and increased awareness of potential renal involvement during CAR-T cell therapy, even in the absence of overt AKI. This case suggests that CAR-T cell therapy may be feasible in selected patients with a solitary kidney under careful monitoring.

Case presentation

A 60-year-old patient with a history of living kidney donation presented with abdominal discomfort, and an abdominal mass was detected by computed tomography (CT) at an external hospital in December 2017. Pathological examination confirmed non-Hodgkin’s lymphoma (NHL), specifically diffuse large B-cell lymphoma (DLBCL) of the non–germinal center B-cell-like (non-GCB) subtype (stage IIA; International Prognostic Index [IPI] score: 2; HCT-Comorbidity Index [HCT-CI] score: 0). At baseline, the patient had a solitary kidney and a history of hypertension. Renal function was stable, with a serum creatinine of 101 μmol/L and an eGFR of 67.4 mL/min/1.73 m², corresponding to G2 kidney function. Urinalysis was normal without proteinuria. The patient received four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and one cycle of RGDP (rituximab, gemcitabine, dexamethasone, and cisplatin). Despite these treatments, disease progression was observed, and he was referred to our hospital in April 2018 for CAR-T cell therapy. Baseline PET/CT (April 2018) demonstrated a large hypermetabolic abdominal mass with additional metabolically active lymph nodes along the right iliac vessels, consistent with lymphoma involvement. To reduce tumor burden, 600 mg rituximab was administered. The patient underwent lumbar puncture with intrathecal chemotherapy and received local radiotherapy to the iliac vascular mass. To mitigate antigen escape in the relapsed or refractory setting ⁹ , the patient subsequently received lymphodepleting chemotherapy with fludarabine and cyclophosphamide (FC regimen), followed by infusion of a total of 6.5 × 10⁶/kg CD22 CAR-T cells and 4.15 × 10⁶/kg CD19 CAR-T cells (investigational) on 6 June 2018 (Day 0). Following CAR-T cell infusion, the patient developed only mild cytokine release syndrome (CRS, Grade 1), manifested as low-grade fever (Figure 1). Serial monitoring of serum creatinine, eGFR, urinalysis, and proteinuria demonstrated stable renal function throughout the peri-CAR-T period without KDIGO-defined AKI (Figure 2). The patient was closely monitored for ICANS and TLS, neither of which occurred. Abdominal ultrasonography revealed a left iliac vascular parenchymal lesion (lymphoma, based on the medical history), and the mass was smaller than before. PET/CT performed on Day +138 revealed soft tissue nodules in the right abdominal cavity with irregular metabolism (Lugano score 5). The right abdominal nodule was identified as a suspicious new lesion following comparison with previous PET/CT findings (April 2018); the mass at the entrance of the original pelvic cavity and the lymph nodes beside the right iliac vessels were significantly smaller or had disappeared, with decreased metabolic activity. After CAR-T cell therapy, the patient received consolidation treatment with the PD-1 inhibitor sintilimab and chidamide, along with local radiotherapy at an external hospital (total dose 18 Gy over 20 days). At Day +201, approximately 0.8% of the T lymphocytes were CAR-T cells, the proportion of mature lymphocytes was low, and the distribution of T lymphocyte subsets was normal. The proportion of CD19⁺ B cells was low. Subsequent CT at Day +203 confirmed a significant reduction in the pelvic mass compared with baseline. PET/CT at Day +267 demonstrated persistent mesenteric nodular lesions with heterogeneous hypermetabolism (Lugano score 5). The proportion of CAR-T cells was 0.5%, the proportion of mature lymphocytes was decreased, while T-cell subset distribution remained within the normal range, and the proportion of CD19⁺ B cells was reduced. At Day +321, bone marrow cytology revealed severely decreased hematopoietic activity. Flow cytometry of both peripheral blood and bone marrow showed no evidence of abnormal monoclonal B-cell populations. CD19⁺ B cells were undetectable, and CAR-T cells accounted for 0.4% of total T lymphocytes. At Day +391, PET/CT demonstrated further metabolic improvement, with residual nodular lesions in the abdominal cavity and mesentery showing only mildly increased uptake (Lugano score 4), consistent with a partial metabolic response approaching complete remission.

Figure 1.

Dynamic changes in IL-6 and ferritin levels during CAR-T cell therapy.

Figure 2.

Dynamic changes in serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) during CAR-T therapy.

Discussion

AKI has been reported in approximately 5% to 33% of patients receiving CAR-T cell therapy ¹⁰ . Gutgarts et al. ¹¹ reported that among 46 adult patients with non-Hodgkin lymphoma treated with CAR-T cells, the cumulative incidence of AKI was 30%, including 21.7% with grade 1 and 8.7% with grade 2/3 AKI. A previous study demonstrated that, in patients with DLBCL, baseline renal function did not significantly influence post-CAR-T renal outcomes or treatment efficacy; however, the development of AKI was associated with worse clinical outcomes ¹² . A systematic review by Portuguese et al. showed that CD19 CAR-T therapy may be feasible and effective in select solid organ transplant recipients, including kidney transplant patients, with high objective response rates and manageable toxicity ¹³ . This supports the potential applicability of CAR-T therapy in transplant populations with careful multidisciplinary monitoring.

At our center, this patient represents, to our knowledge, the first reported case of CAR-T cell therapy in an individual with a solitary kidney. Given the patient’s limited renal reserve and primary chemo-refractory disease, CAR-T cell therapy was selected as the treatment strategy. Although the patient did not have a history of organ transplantation, he had a solitary kidney with reduced renal reserve—a condition similarly underrepresented in CAR-T cohorts. Given this high-risk profile, we implemented an intensified renal protection protocol, including daily renal function monitoring, individualized hydration based on volume status, strict avoidance of nephrotoxic agents, and cautious use of contrast media. Importantly, he completed CAR-T therapy without developing overt AKI, suggesting that CAR-T therapy may be a feasible treatment option in carefully selected patients with organ impairment. This case underscores the importance of close renal monitoring and adds to the limited clinical experience for the management of patients with limited renal reserve who are considered for CAR-T therapy.

As discussed above, renal injury associated with CAR-T cell therapy is multifactorial. These mechanisms highlight the importance of early recognition of high-risk features and timely preventive interventions in vulnerable patients. Therefore, close monitoring of renal function and electrolyte balance, together with early individualized preventive and supportive interventions, may mitigate renal injury in patients undergoing CAR-T cell therapy. Baseline assessment of renal function and dynamic monitoring of metabolic parameters may facilitate early risk stratification ¹⁴ . When AKI occurs, prompt identification of underlying causes and timely supportive management, including appropriate fluid resuscitation and anti-cytokine therapy, may contribute to renal recovery, with most CAR-T-associated cases appearing to be reversible ¹⁵ .

The patient also received immunotherapy and radiotherapy after CAR-T treatment, which may have influenced the observed clinical response. PD-1 blockade may enhance T-cell function ¹⁶ . However, given the limited clinical evidence, the extent to which these factors contributed to the outcome in this case remains uncertain.

Future prospective studies are needed to establish reliable predictive models and biomarkers, particularly in high-risk populations with limited renal reserve. Moreover, improved understanding of the pathophysiological mechanisms underlying CAR-T-associated renal complications may further optimize individualized management strategies.

Conclusion

This case describes a patient with a solitary kidney and hypertension who developed DLBCL and was treated with CAR-T cell therapy. The treatment was well tolerated, with only mild CRS. No AKI or clinically relevant renal dysfunction was observed, and renal function remained stable throughout the treatment course. This case may provide useful clinical experience for the management of similar patients.