Objective
Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been ...excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer.
Methods
A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response.
Results
The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation.
Conclusion
Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
Nocardiosis mycetoma in an immunocompetent patient Guicheney, Marie; Peuchant, Olivia; Guillotin, Vivien ...
International journal of dermatology,
January 2022, Letnik:
61, Številka:
1
Journal Article
Summary
Background
Primary cutaneous peripheral T‐cell lymphomas with a T‐follicular helper phenotype (pcTFH‐PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis ...fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T‐cell lymphomas (AITL).
Objectives
We describe the clinicopathological features of pcTFH‐PTCL in this original series of 23 patients, and also characterize these cases molecularly.
Methods
Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next‐generation sequencing.
Results
All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T‐cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B‐cell lymphoproliferative disorder (LPD) on biopsy, including Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (n = 3), EBV+ LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2–RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2–RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1).
Conclusions
Patients with pcTFH‐PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH‐PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate.
What is already known about this topic?
There is a group of cutaneous lymphomas that express T‐follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities.
These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4+ small/medium‐sized T‐cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T‐cell lymphomas (PTCL) with TFH phenotype.
What does this study add?
This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH‐PTCL) to be molecularly characterized.
pcTFH‐PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T‐cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma.
This has an impact on the treatment and follow‐up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management.
There is a group of cutaneous lymphomas that express TFH markers that do not appear to correspond to existing WHO diagnostic entities. This is the first large original series of patients with a diagnosis of primary cutaneous peripheral T‐cell lymphomas with a T‐follicular helper phenotype (pcTFH‐PTCL) to be molecularly characterised. pcTFH‐PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, and does not belong to known diagnostic groups of cutaneous lymphoma.
Linked Comment: W. Kempf. Br J Dermatol 2022; 187:841–842.
Plain language summary available online
Background
The clinical benefit of cusatuzumab, a CD70‐directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T‐cell ...lymphoma (CTCL).
Methods
In this cohort expansion of the ARGX‐110‐1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed.
Results
The most common adverse events included infusion‐related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1‐3) were reported in 11 patients; 1 of these (vasculitis) was considered drug‐related. For 8 of the 11 patients receiving 1 mg/kg, anti‐drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses.
Conclusions
Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose‐dependent effect on exposure supports the use of 5 mg/kg for future development.
Cusatuzumab, a monoclonal antibody targeting CD70, is well tolerated and shows dose‐dependent evidence of antitumor activity in a heavily pretreated patient population with cutaneous T‐cell lymphoma. The overall response rate was 23% with increased efficacy in patients with Sézary syndrome, warranting further clinical development.
The two clinico‐pathological patterns are ‘Sweet‐like syndrome’ and ‘Multiple COVID‐Arm’. ‘Sweet‐like syndrome’ presents clinically as erythematous and oedematous papules or plaques, sometimes ...developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte‐like immature myeloid cells consistent with a histiocytoid Sweet syndrome. ‘Multiple COVID‐arm’ is characterized by multiple large inflammatory plaques with histological analyses showing a perivascular and interstitial inflammatory infiltrate with eosinophils.
Article Note: Conflict of interest: None. Funding source: None. Byline: Camille Luherne, Sarah Menguy, Julien Seneschal, Anne Pham-Ledard, Marie Beylot-Barry
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