Diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype, involving the nasal cavity and sinuses-02

In March 2021, a 52-year-old male patient from Northeast China presented with nasal mass discovered during a routine check-up. He experienced symptoms of nasal congestion, headaches, blurred vision, and night sweats, without fever or weight loss.

Initial examinations revealed extensive soft tissue mass involving the right nasal cavity and sinuses, affecting critical structures such as the orbit, anterior skull base, sphenoid sinus, and left ethmoid sinus on MRI. Pathological examination of the right maxillary sinus suggested diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype.

Immunohistochemistry (IHC) indicated high invasiveness with double expression of Ki-67 (90%+), CD20 (+), c-Myc (>80%+), Bcl-2 (>90%), Bcl-6 (+), CD10 (-), Mum1 (+), CD79a (+), CD30 (-), and CyclinD1 (-), with no detectable Epstein-Barr virus-encoded small RNA (EBER).

Fluorescence in situ hybridization (FISH) detected Bcl-6 and c-myc translocations, but no Bcl-2 gene translocation. Next-generation sequencing (NGS) confirmed mutations in MYD88, CD79B, IGH-MYC, BAP1, and TP53 genes, indicating a high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations.

Positron emission tomography-computed tomography (PET-CT) depicted irregular soft tissue masses in the right nasal cavity and superior sinus, approximately 6.3x3.8cm in size, with indistinct borders. The lesion extended upwards into the right ethmoid sinus, outwardly to the medial wall of the orbit and intraorbital region, and posteriorly to the sphenoid sinus and skull base. The lesion exhibited increased fluorodeoxyglucose (FDG) uptake with an SUVmax of 20. Mucosal thickening was noted in the left ethmoid and superior sinus, with normal FDG metabolism.

The patient had previously undergone R2-CHOP, R-ESHAP, BEAM+ASCT, and local radiotherapy, with disease progression observed. Due to chemotherapy resistance and extensive multi-organ involvement (including lungs, liver, spleen, and bones), the patient was diagnosed with primary refractory DLBCL. The disease progressed rapidly with high invasiveness, elevated LDH levels, a modified International Prognostic Index (NCCN-IPI) score of 5, TP53 mutation, and MCD subtype, experiencing relapse within 6 months post-autologous transplantation.

Following bridging therapy, the patient briefly received steroid treatment with poor response. Later treatment included CD79 monoclonal antibodies combined with bendamustine and mechlorethamine hydrochloride, resulting in a significant reduction in LDH levels and noticeable tumor shrinkage.

After successful preparation of CAR-T therapy, the patient underwent lymphocyte depletion (lymphodepletion) chemotherapy with the FC regimen, achieving the intended lymphocyte clearance and subsequent severe leukopenia. However, three days before CAR-T infusion, the patient developed fever, herpes zoster in the lumbar region, and elevated serum lactate dehydrogenase (LDH) levels up to 25.74ng/ml, indicating a possible mixed-type active infection adverse event (AE). Considering the increased risk of CAR-T infusion due to active infection, potentially leading to fatal outcomes, the patient received broad-spectrum antibiotics covering various pathogens.

Following CAR-T infusion, the patient developed high fever on the infusion day, progressing to dyspnea, hemoptysis, and worsening pulmonary symptoms by day three. Pulmonary venous CT angiography on day five revealed scattered ground-glass opacities and interstitial changes, confirming pulmonary hemorrhage. Despite initial avoidance of steroids due to potential CAR-T suppression, and supportive treatment focused on anti-infection management, the patient's condition showed limited improvement.

On day seven, significant CAR gene copy number expansion was detected in peripheral blood, prompting a treatment adjustment with low-dose methylprednisolone (40mg-80mg). Five days later, bilateral lung rales decreased, and hemoptysis symptoms were notably controlled.

By day eight, CAR-T therapy demonstrated remarkable efficacy. Within just one month of CAR-T treatment, the patient achieved complete remission (CR). Subsequent examinations up to July 2023 confirmed the patient remained in CR, indicating a deep response to CAR-T therapy and potential for cure.