Failure of Single-Agent Rituximab for Treatment of Subcutaneous Intravascular Lymphomatosis (IVL): A Case Report.

IVL is an uncommon large-cell lymphoma, usually of B-cell origin. Typically, the CD20+ lymphoma cells possess defects in homing receptors. This leads to limited cell migration from the vessel endothelium, resulting in cell crowding and blockage of intravascular lumens. Patients frequently present with skin lesions, fever, and neurological dysfunction, reflecting the ability of malignant cells to infiltrate various organs. The wide spectrum of clinical manifestations of IVL, along with its propensity to afflict elderly patients with multiple comorbidities, presents a diagnostic and therapeutic challenge; most cases are discovered post-mortem. Anthracycline-based chemotherapy is the standard treatment for this malignancy, but outcomes are disappointing, with most patients destined to die from progressive lymphoma and, less commonly, chemotherapy-induced complications. An 86-year-old female underwent a lesion biopsy after bilateral thigh plaques (the largest of which measured 8 × 13 cm) became increasingly erythematous and painful, despite treatment with antibiotics and corticosteroids. She was diagnosed with subcutaneous CD20+ IVL. Laboratory studies were notable for hematocrit 29% with iron indices consistent with inflammatory block, lactate dehydrogenase 950 IU/L (normal < 240 IU/L) and β2-microglobulin 1.8 mg/mL (normal < 2.0mg/mL). Whole-body computed tomography and positron emission tomography fusion studies did not suggest lymphoma elsewhere. She received rituximab (375 mg/m²/week × 8 weeks) and achieved a complete remission (CR), with the disappearance of thigh discomfort and resolution of her medial thigh plaques. Three months after completion of rituximab treatment, a new left posterior chest wall mass was biopsied and proved to be recurrent IVL. She declined further treatment and was referred to hospice care. Through a Medline search we were able to identify 12 additional patients who were treated with multi-agent chemotherapy and rituximab (n=10) or rituximab monotherapy (n=2). The patients’ ages ranged from 42 to 86 years. The most common clinical presentations in these cases included fever (n=5), nervous system involvement (n=3), and skin rash (n=2). Excluding one multi-agent therapy patient who died during treatment, all patients in our search achieved CRs, with a median follow-up duration of 14 months (range, 6–36 months). Among various lymphoma subgroups (including elderly patients with high-risk features and those with IVL), rituximab has been used as a single agent and to augment the anti-lymphoma properties of multi-agent chemotherapy. Our case report is the first to describe IVL recurrence following rituximab monotherapy, and highlights the need for further investigation on the use of rituximab in the treatment of this rare lymphoma.