No formal hypothesis testing was performed

No formal hypothesis testing was performed. siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (= 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. Conclusions All MCD patients in this extension study have received siltuximab for a prolonged duration Gypenoside XVII (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab. = 8) and corticosteroids (= 6) were the most commonly used (Table ?(Table1).1). Of these 19 patients, 10 (53%) had hyaline vascular and 9 (47%) had plasmacytic histological subtype. Five patients had a body mass index (BMI) 40 when entering the extension study, and an additional 3 had a BMI 30. Table 1 Patient demographic and disease characteristics at start of initial siltuximab treatment = 19)(%) or median [range]. aPatients who had not received any prior systemic therapy. At the time of enrollment in the extension study, the 19 participating patients had received a median of 58 (range 29, 97) doses of siltuximab Gypenoside XVII over a median of 3.3 (range 1.6, 5.0) years while in the phase 1 study. From the start of the phase 1 study to the data cutoff for the current interim analysis (January 2013), these patients received a median of 81 (range 49, 129) doses of siltuximab over a median of 5.1 (range 3.4, 7.2) years, with 14 (74%) of patients treated for longer than 4 years. At the time of the analysis, 11 patients received treatment at q3wks dosing and 8 patients received treatment at q6wks dosing (for 1 patient, this meant a continuation of the dosing interval within the phase 1 study). Among these 8 patients, the median treatment duration on the extended (q6wks) dosing interval was 11 months (range 5.8 months to 3.8 years). Of note, 1 additional patient started in this study with 4 cycles q6wks dosing and continued with q3wks dosing. All 19 patients are alive and continue to receive siltuximab treatment. Safety Over the combined time course of the phase 1 and extension studies (median 5.1 years; range 3.4, 7.2 years), all patients reported at least 1 AE of any grade, with upper respiratory Rabbit Polyclonal to Cytochrome P450 4Z1 tract infection (90%); nausea (63%), vomiting (58%); diarrhea (53%); hypercholesterolemia (total cholesterol; 47%); and pain in extremities, hypertriglyceridemia, headache, rash, and hepatic function abnormal (42% each) being the most commonly reported (Figure ?(Figure1).1). The most common AEs ( 20%) reported in the extension study alone were upper respiratory tract infection (63%); diarrhea (32%); and fatigue, arthralgia, and pain in extremities (21% each). Those considered at least possibly attributed to siltuximab were reported in 6 patients during the extension study and included pneumonia, tooth abscess, constipation, increased hemoglobin, hypertriglyceridemia, hyperbilirubinemia, chronic otitis media, and upper respiratory tract infection (5% each) and grade-3 leukopenia and lymphopenia (5% each). When assessed by length of patient treatment/follow-up, the incidences of AEs for the different system organ classes were similar or lower during the treatment periods of 2C4 years and 4 years when compared with the initial 2 years of treatment (Table ?(Table2).2). In most patients, the highest grade of AE reported was either grade 2 (37%) or grade 3 (53%); 2 (11%) patients had a grade-4 AE. Grade-3 AEs were most commonly reported in the following system organ classes: gastrointestinal, 6 (32%); infections, 5 (26%); blood/lymphatic system, 4 (21%); and general disorders/administration-site, 4 (21%). Most grade-3 AEs were each reported in only 1 patient; exceptions included Gypenoside XVII 3 (16%) patients with hypertension and 2 (11%) patients each with nausea, cellulitis, and fatigue. No patient developed an infusion-related reaction, nor did any patient develop antibodies against siltuximab during the extension study. Open in a separate window Figure 1 Adverse events considered at least possibly attributed to siltuximab for those events reported by 10% of patients across both the phase 1 and extension studies (= 19)aIn addition, the adverse events of bone pain, herpes zoster, lymphopenia, rectal abscess, anal fistula, cardiac disorder, mitral valve incompetence, oral candidiasis, sinus bradycardia, chronic otitis media, irritable bowel syndrome, urobilinogen urine, decreased blood immunoglobulin M, and infusion-related reaction (5% Gypenoside XVII each) and a serious.