Bevacizumab, pertuzumab, and octreotide depot was well-tolerated with a 16% ORR. Results in the well-differentiated carcinoid tumors are thought provoking.
Human herpes virus-8 (HHV8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder sustained by pro-inflammatory cytokines, including interleukin-6 (IL-6). According to the international evidence-based criteria developed by the Castleman Disease Collaborative Network (CDCN), siltuximab, which works by inhibiting IL-6, is the recommended choice for iMCD treatment. We report a case of a 63-year-old white male with iMCD who has been on maintenance therapy with siltuximab for 15 years – representing one of the longest treatment periods of any patient with iMCD treated with siltuximab. The patient initially presented with fatigue and night sweats, with progressive worsening of the symptoms. Whole-body positron emission tomography/computed tomography revealed hypermetabolic lymphadenopathy. The patient had histopathologically confirmed Castleman disease, plasma cell type, and was negative for HHV8 and human immunodeficiency virus. The patient had abnormally high C-reactive protein (CRP) levels, a surrogate measure for IL-6. The patient was treated with high-dose steroids but had recurring lymphadenopathy early on. He was enrolled in the phase I dose-finding clinical trial of siltuximab, during which he achieved marked clinical improvement and sustained inhibition of CRP. The patient was enrolled in the long-term safety study and continues to receive siltuximab at 11 mg/kg every 3 weeks. He is presently receiving commercial siltuximab and has remained asymptomatic, with no evidence of lymphadenopathy. The case study presented is consistent with the evidence that siltuximab is a safe and effective therapy for the long-term management of iMCD. In addition, this case highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available for patients as described in the CDCN and National Comprehensive Cancer Network iMCD treatment guidelines. Plain Language Summary The case of a 63-year-old white male with idiopathic multicentric Castleman disease who was successfully treated with siltuximab for 15 years Idiopathic multicentric Castleman disease (iMCD) is a group of rare lymphoproliferative disorders with shared histopathological features that affect lymph nodes in multiple regions of the body. The signs and symptoms of iMCD can be varied, with the disease being mild in some patients while life-threatening in others. A timely diagnosis of iMCD can be challenging but is required for effective management. We report a case of a patient who was diagnosed with iMCD. The patient was given high-dose steroids but continued to show progressive disease. He was then started on siltuximab, a targeted antibody therapy against a specific cytokine (interleukin-6) involved in inflammation. The patient responded well to the treatment, has shown evidence of long-term disease control, and has not reported any serious adverse events related to long-term siltuximab use. He has received 11 mg/kg of siltuximab every 3 weeks for the past 15 years. This case emphasizes the value of using siltuximab therapy for long-term management of this rare disorder. In addition, it highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available, as described in iMCD treatment guidelines.
4127 Background: Targeted agents are used to treat well-differentiated NET. Octreotide binds somatostatin receptors and improves time to progression (TTP) of carcinoid tumors, and VEGF pathway targeting improves TTP of pancreatic NET. HER2 overexpression is reported in NET, and pertuzumab blocks HER2 receptor dimerization. This phase II trial combined bevacizumab, pertuzumab, and octreotide LAR for pts with advanced NET. Methods: Pts with advanced well-differentiated NET were enrolled. Pts had ECOG 0-1, and normal end-organ function, including left ventricular ejection fraction (LVEF) ≥50%. Pts received bevacizumab 15 mg/kg IV, pertuzumab 420 mg IV (following an 840 mg loading dose) day 1 of a 21 day cycle, and octreotide LAR 30 mg IM every 28 days. Primary endpoint was objective response rate (ORR). Results: Between 6/10 and 4/11, 43 pts enrolled. 22 M/21 F, med age 62 (33-88), 32 (74%) carcinoid, 11 (26%) PNET. 26% had prior sandostatin, 72% prior surgery, 19% prior radiation, 23% with > 2 previous systemic therapies. Treatment-related grade 3 toxicities included: hypertension (28%), LVEF dysfunction (9%) (reversible with trial drug hold), and diarrhea (7%). No grade 4 toxicity was reported. Median treatment duration was 38 weeks (range: 0 – 76). Chromogranin A values were elevated in 27 pts; 59% had decreases during treatment. Seven pts (16%) achieved objective response [CR: 1 carcinoid (2%), PR: 6 (4 carcinoid, 2 PNET) (14%)]. ORR for carcinoid pts was 15.6%. Median PFS for the entire group was 8.2 months (95% CI: 6.3 – NA). PFS for carcinoid pts was 8.5 months (95% CI: 6.3 – NA); PFS for PNET pts was 6.4 months (95% CI: 3.9 – NA). Median OS has not been reached at 14.3 months followup. Conclusions: The ORR of the combination of bevacizumab, pertuzumab, and octreotide LAR in NET pts was encouraging. Particularly the response rate in carcinoid pts appears higher than historical data, warranting further investigation of this regimen in these pts.
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