CUTANEOUS INVOLVEMENT IN MULTIPLE MYELOMA IN THE ERA OF PROTEASOME INHIBITORS: HAS THE DISMAL PROGNOSIS CHANGED?

Abstract

We present a 3-case series of MM with cutaneous involvement and a wide range of clinical manifestations and dismal prognosis after cutaneous involvement. Case 1- A 55-year-old man presenting with symptomatic MM, IgG- kappa, Durie-Salmon IIIA stage, and ISS = 3. He was treated with CyBORD, 4 cycles with complete response. Subsequently, he underwent HSCT whose conditioning was performed with MEL 200 mg/m 2 and infusion of 12 x 10 6 CD34/kg cells. After HSCT, he remained in complete response and maintenance with bortezomib. After 4 months, he developed erythematous infiltrated plaque that evolved to an exophytic tumor on the left posterior axillary line. In addition, sudden spinal cord compression on T12 level whose radiological investigation demonstrated bone plasmacytoma was also observed. Decompressive laminectomy and skin lesion biopsy were performed, which confirmed the presence of cutaneous infiltration by MM. Hence, the patient received a third-line treatment with DVd. The patient's renal function deteriorated and his skin lesions showed progressive growth. Eventually he became septic and died. Case 2- A 76-year-old man diagnosed with IgA/lambda secreting MM with Durie Salmon IIIA and ISS II. His initial treatment consisted of an association of melphalan, prednisone and bortezomib, which resulted in complete remission. A few months later, the patient relapsed leading to further treatment with lenalidomide and dexamethasone. At that moment, the patient showed no response and underwent a regimen containing KRD, which was unsuccessful. The association of dara-VMP was used after he developed renal failure, cardiovascular impairment and skin lesions over his legs were noted. A fine needle aspiration was performed and microscopic analysis showed signs of cutaneous plasmacytosis confirming cutaneous infiltration by MM. The patient developed multiple organ failure after sixty days of the onset of such cutaneous lesions. Case 3- A 50-year-old woman with a diagnosis of IgA secretory MM, Durie Salmon IIIB, ISS 3. Initial therapeutic approach was performed with thalidomide and dexamethasone. A partial response with stabilization of heavy and light chain monoclonal protein. A few months later, her condition deteriotated. Thus, a protocol with CYBORD was introduced. Despite treatment, she developed purplish plaques and nodules on the left anterior chest wall and over both arms, which evolved with rapid growth. Biopsy of the cutaneous lesions was performed, which revealed an extramedullary plasmacytoma. Afterwards, a more aggressive therapeutic regimen was applied containing melphalan, vincristine, cyclophosphamide and methylprednisolone with no clinical response.Ultimately she died of sepsis. Cutaneous plasmacytic infiltration in multiple myeloma (MM) is a rare clinical condition, usually associated with a high burden of malignant cells and a poor prognosis. The clinical management of the secondary infiltration of the MM does not have a standard optimal therapeutic regimen. There are some physiopathologic hypothesis that arise that cutanea infiltracao is owemore aggressive forms of myeloma usually with characteristics of plasmablasts and clones with high prevalence of high-risk molecular markers. In our experience, the use of these drugs has not translated into additional survival to patients, underscoring the role of skin involvement as a poor prognostic factor.