Paraneoplastic necrobiotic xanthogranuloma in multiple myeloma: a rare case report of successful treatment of relapse with carfilzomib, lenalidomide and dexamethasone

Necrobiotic xanthogranuloma is a rare non-Langerhans cell histiocytosis (CD68-positive, CD1a-negative) characterized by yellow to red-brown papules, plaques and nodules with telangiectasias, most commonly affecting the periorbital region (80-85% of cases), but it can also involve the face, trunk and extremities.(1) Although accumulating evidence, primarily from case reports of bortezomib-based regimens and intravenous immunoglobulin with or without ruxolitinib, suggests favorable outcomes in newly diagnosed multiple myeloma with associated necrobiotic xanthogranuloma (2-4) evidence to guide the management of relapsed disease remains scarce.

A 49-years-old man was diagnosed with multiple myeloma associated with paraneoplastic cutaneous necrobiotic xanthogranuloma. According to local treatment guidelines, patient received four cycles of bortezomib, thalidomide, and dexamethasone (VTD) as first-line therapy, achieving a partial response. To deepen the response, he underwent autologous stem cell transplantation (ASCT) with high-dose melphalan (200 mg/m²), resulting in complete remission (CR) of both the hematologic disease and the cutaneous lesions.

Seven years after ASCT, the patient developed new cutaneous lesions (ranging in color from red-brown to yellow plaques) on the arms, legs and periorbital region. Skin biopsy confirmed recurrent necrobiotic xanthogranuloma. Simultaneously, first relapse of multiple myeloma was confirmed by serum protein electrophoresis.

Second-line treatment with carfilzomib 27 mg/m² D1-2, D8-9, D15-16, lenalidomide 25mg D1-21, and dexamethasone 40mg D1, D8, D15 (KRd) was initiated.

After four cycles of KRd, the patient achieved a very good partial response. To further improve the treatment response, patient underwent a second ASCT with high-dose melphalan (200 mg/m²), followed by eight cycles of KRd maintenance therapy.

Following treatment, the patient achieved a second CR. The cutaneous lesions resolved and repeat biopsies from the previous lesion sites demonstrated no residual necrobiotic xanthogranuloma.

The patient has remained in complete clinical remission for more than 3.5 years after KRd-based therapy, with no recurrence of cutaneous paraneoplastic manifestations. No grade 3 or higher treatment-related adverse events were observed.

This case suggests that KRd-based therapy, combined with ASCT, may provide durable disease control and complete resolution of paraneoplastic necrobiotic xanthogranuloma in patients with relapsed multiple myeloma. Further studies are needed to define optimal management.