To our knowledge, we report the first case of sarcoid-like granulomatous reaction induced by nivolumab, a fully human IgG4 anti-programmed death 1 (PD-1) immune checkpoint inhibitor antibody. A ...57-year-old man was treated with nivolumab 3 mg/kg for 2 weeks for a desmoplastic melanoma stage III American Joint Commission on Cancer, with no BRAF , NRAS , and cKit mutations. At 10 months, although melanoma complete response was achieved, he developed sarcoid-like granulomatous reaction in the mediastinal lymph node and skin, which resumed after nivolumab arrest. Melanoma did not relapse after 12 months of follow-up. Considering the recently demonstrated role of activated PD-1/PDL-1 axis in sarcoidosis, granulomatous reaction in the patient seems to be a paradoxical reaction, but similar observations have been reported with ipilimumab, another immune checkpoint inhibitor. Sarcoid-like granulomatous reaction during immunotherapy treatment could be a manifestation of cell-mediated immunity induced by these drugs. Impact of granulomatous reaction induced by immune checkpoint inhibitor on melanoma progression is not known and requires further study. Melanoma patients treated by immunotherapy (anti-cytotoxic T-lymphocyte-associated protein-4/anti-PD-1) should be considered for developing sarcoid-like granulomatous reaction that must not be confused with tumor progression.
BACKGROUND Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. The objective of this study was to evaluate the efficacy and safety of thalidomide in ...severe cutaneous sarcoidosis. METHODS This study consisted of a randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicenter trial lasting 3 months and an open-label study from month 3 to month 6. Adults with a clinical and histologic diagnosis of cutaneous sarcoidosis were included in nine hospital centers in France. Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for 3 months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide, 100 mg to 200 mg daily. The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement in three target lesions scored for area and infiltration, were compared across randomization groups. RESULTS The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients in the thalidomide group (20%) vs four out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of −1% 95% CI, −26% to +24% for thalidomide vs placebo, P = 1.0). Eight patients with side effects were recorded in the thalidomide group vs three in the placebo group. We observed a large number of adverse event-related discontinuations in patients taking thalidomide in the first 3 months (four patients with thalidomide, zero with placebo) and in the 3 following months (five patients). CONCLUSIONS At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. TRIAL REGISTRY ClinicalTrials.gov ; No.: NCT0030552; URL: www.clinicaltrials.gov
Background Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of ...pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH (PLCH-PH) remain unknown. Methods Consecutive patients with PLCH with PH confirmed by right-sided heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed. Results Twenty-nine patients were studied. Baseline characteristics of patients with PLCH-PH were as follows: 83% of patients in World Health Organization (WHO) functional class III to IV, mean 6-min walk distance of 355 ± 95 m, mean pulmonary arterial pressure (mPAP) of 45 ± 14 mm Hg, cardiac index of 3.2 ± 0.9 L/min/m2 , and pulmonary vascular resistance (PVR) of 555 ± 253 dyne/s/cm5 . Use of PAH therapy in 12 patients was followed by an improvement in mPAP (56 ± 14 mm Hg and 45 ± 12 mm Hg, P = .03) and PVR (701 ± 239 dyne/s/cm5 and 469 ± 210 dyne/s/cm5 , P = .01) between baseline and follow-up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3-, and 5-year survival estimates of the 29 patients were 96%, 92%, and 73%, respectively. Except a trend toward a better survival rate associated with the use of PAH therapy, WHO functional class was the only variable significantly associated with death. Conclusions In this group of patients, PAH therapies improved hemodynamics without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified. Prospective clinical trials focusing on this population of patients are warranted.
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