Alessandro Moscetti

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

BackgroundImmunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes.Design and methodsSeventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group.ResultsMedian age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT.ConclusionsDespite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.

Quick response to bortezomib plus dexamethasone in a patient with AL amyloidosis in first relapse.

High-dose melphalan followed by autologous stem cell transplantation is currently the treatment of choice in fit patients affected by AL amyloidosis. However, the majority of AL amyloidosis patients is ineligible for transplant or experience relapse after this kind of treatment. A new treatment approach is represented by bortezomib, a proteasome inhibitor widely used in multiple myeloma. We used a combination therapy of bortezomib and dexamethasone in a 66-years-old woman affected by systemic AL amyloidosis and relapsed after nine courses of oral melphalan and dexamethasone. The patient received only two courses of bortezomib and dexamethasone due to severe somatosensory polyneuropathy development. Anyway complete remission (CR) and organ response were both achieved after 1.5 and 2.5 months, respectively. Disease relapse occurred after 7 months of a CR period. The excellent response obtained with bortezomib and dexamethasone in a pretreated and relapsed patient represents a new chance of treatment in AL amyloidosis even though it is complicated by multiorgan impairment. Introduction: Primary systemic AL amyloidosis is clinically characterized by progressive dysfunction of multiple visceral organs, including heart, kidneys, liver, and gastrointestinal (GI) tract, and it is pathologically caused by amyloid deposition in various tissues due to the presence of an underlying plasma cell dyscrasia in the bone marrow [1,2]. Prognosis is poor, particularly in patients with cardiac involvement [3,4]. Prompt initiation of treatment is required in systemic form in order to inhibit the growth of malignant clone and to reduce the supply of the amyloidogenic light chains. Treatment choice depends on patient’s age and performance status like on the type and extent of organ damage. The therapeutic armamentarium has greatly expanded in recent years from melphalan–prednisone as single resource in 1977 to several effective therapies including highdose dexamethasone-based regimens combined with melphalan (MDex), thalidomide (ThalDex), and cyclophosphamide-thalidomide (CTDex), high-dose melphalan followed by autologous stem cell transplantation (SCT), to the new agents basically represented by lenalidomide and bortezomib [5]. Bortezomib is a small boronic acid derivative that inhibits the 26S proteosome which can produce clinically useful remissions in patients with relapsed myeloma [6,7]. Bortezomib has efficacy in myeloma refractory to thalidomide [8] but has substantial, although often manageable, toxicity [9]. Encouraging data from myeloma suggested that it might also be a useful agent in AL amyloidosis. Kastritis et al. reported for the first time the efficacy of the proteasome inhibitor in patients with AL amyloidosis. The hematologic response rate was observed in 94%, including a 44% CR. The median follow-up was 11.2 months [10]. Wechalekar et al. conducted a trial in which heavily pretreated patients received bortezomib with or without dexamethasone. Bortezomib was median the third-line therapy (range 1–6). Seven out of nine (77%) patients who were given the combination of Btz/Dex responded. The median survival was not reached at 24 months from the end of treatment [11]. Lamm et al. reported a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis. Eighteen patients (69%) received Btz/Dex as first-line treatment. The overall response rate was 54%, with eight patients achieving a hematologic complete remission. All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in three patients (12%). Toxicities were manageable, with hematological side effects being most common [12]. Methods: Between September and October 2007, at Clinical Haematology Department – Sant’Andrea Hospital in Rome, we treated a 66-years-old woman with relapsed systemic AL amyloidosis with two courses of a combination therapy based on bortezomib (1.3 mg/m day 1, 4, 8, 11 q21) plus dexamethasone (20 mg p.o. day 1–2, 8–9 q21). Before bortezomib plus dexamethasone, the patient had been treated with 9 courses of oral melphalan (0.18 mg/kg day 1–4 q28) and dexamethasone (40 mg p.o. day 1–4 q28) as first-line treatment and disease relapse occurred after a 19 months’ complete remission period (Table 1). During treatment, patient received anti-infective prophylaxis with cyprofloxacine 250 mg b.i.d from day 1 to day 9 of every cycle and with acyclovir 200 mg b.i.d continuously for HVZ virus reactivation. Baseline evaluation included serum and urine immunofixation and electrophoresis, liver and renal function assessment, ECG, cardiac and abdominal ultrasonography, (Figure 1) and bone marrow aspirate. Plasmatic NT-proBNP and troponine I were used for heart disease assessment and response to treatment. Full blood count, biochemical survey, and serum free light chains (sFLC) were assessed before and after the end of treatment. 152

Pseudoxanthoma Elasticum and Light-Chain Amyloidosis

Pseudoxanthoma elasticum is a heritable disorder of connective tissue characterized by cutaneous, vascular and ocular changes that result from the accumulation of fragmented elastic fibres. Even though the etiopathogenesis is not still completely understood, in recent years in literature some Authors have considered pseudoxanthoma elasticum as a metabolic disorder. We present the case of a 45-year-old man affected by pseudoxanthoma elasticum and light-chain amyloidosis and we discuss the possible reasons that led to this association.