Durable complete response to combination nivolumab and ipilimumab in metastatic renal cell carcinoma

Immune checkpoint inhibitors, which promote or suppress the anti-tumor immune response, are becoming the mainstay of cancer treatment. In 2018, CheckMate 214 study showed a higher response rate with ipilimumab and nivolumab combination therapy compared to conventional therapy for advanced renal cell carcinoma. We report a case of complete response and durable response for two years to ipilimumab and nivolumab combination therapy in a patient with postoperative renal cancer recurrence that caused immune-related adverse events such as interstitial pneumonia and hepatotoxicity.

Immune-related adverse events caused by combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab for lung cancer

It has been less than a decade since immune checkpoint inhibitors became the mainstay of lung cancer treatment, and 2020 saw the advent of the era of complex immune checkpoint inhibitors. Although clinical trials have shown that the therapeutic effects of complex immune checkpoint inhibitors are favorable, they are associated with an increase in adverse events. The use of combined immune checkpoint inhibitors in clinical practice has progressed slowly, and the frequency and types of adverse events they cause remain unclear. Here we report the adverse events of six patients with lung cancer treated with regimens containing nivolumab and ipilimumab in 2021. Four of the six patients had grade 3 or higher adverse events, including one patient with lung injury and one patient with skin injury, both of whom died. The timing and nature of the adverse events were difficult to predict.

Initiatives for immune-related adverse events by the outpatient pharmacist clinic

Early detection is the key in managing side effects because immune-related adverse events (irAEs) are becoming more serious, and their onset time differs. In our hospital, we conducted an outpatient pharmacist clinic for early detection of irAEs by self-care practice for the cases of immune checkpoint inhibitor administration. As a result of a retrospective survey of 207 cases, the percentage of irAEs found by pharmacist’s suggestion of the outpatient pharmacist clinic increased over time, and a high detection ratio was obtained even for irAEs with a late onset time. The incidence of serious irAEs was higher than that in the immediate post-marketing surveillance, and different factors were considered. Although there were some problems, the outpatient pharmacist clinic had a certain effect.

Daily intake of Citrus jabara fruit peel powder (Japanese Patent No. 5,323,127) improves allergy-like symptoms: A randomized double-blind parallel-group comparative study

Citrus jabara (CJ) is a rare citrus fruit that used to grow naturally only in the southern part of the Kii Peninsula in Japan. Human intervention studies with oral intake of CJ fruit have shown its anti-allergic effects, but the testing method was a pre-post comparison study. In this study, we conducted a randomized, double-blind, parallel-group interventional study to evaluate the volume-dependent effects of oral intake of CJ fruit peel powder (Japanese Patent No. 5,323,127) on nasal and eye allergy-like symptoms. Ninety healthy adults were allocated to three groups and given test foods containing 1,000, 500, and 0 mg of CJ peel powder, with one packet per day for 4 weeks. After excluding those who dropped out or deviated from the study protocol, 73 were included in the efficacy analysis and 86 in the safety analysis. The high-dose group (1,000 mg/day) was significantly lower than the placebo group in the scores of “nasal and eye symptoms” at week 4, and “blocked nose” at weeks 2 and 4 in the evaluation of question I of Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ No. 1). The changes in scores (difference from the pre-observation period) on the Nasal and Eye Symptom Questionnaire showed a dose-dependent reduction in rhinorrhea. In the safety evaluation, there were no significant differences in examinations of physiology, hematology, and blood biochemistry between the groups, and no adverse events attributable to the test foods were observed. These results suggest that intake of CJ peel powder can alleviate allergy-like symptoms.

A case of lichen planopilaris associated with lichen planus following Blaschko lines successfully treated with topical corticosteroid

Lichen planopilaris (LPP) is characterized by erythematous, keratotic follicular papules and cicatricial alopecia. LPP, the most common cause of cicatricial alopecia, is usually seen in women and causes significant psychosocial morbidity. We describe here a 42-year-old woman with a 6-month history of hair loss accompanied by itching on the scalp. Dermatological examination revealed patchy cicatricial alopecia in the vertex and band-like purple flat patches and plaques following the Blaschko lines on the right half of the body, together with post-inflammatory hyperpigmentation. Histopathological examination of the scalp biopsy was consistent with LPP, while thigh biopsy was consistent with lichen planus. With the histopathological and clinical evidence, our patient was evaluated as LPP associated with LP and successfully treated with topical corticosteroid. A few LPP and LP cases following the Blaschko lines have previously been reported separately. However, LPP, together with LP following Blaschko lines, have not been reported in the same patient.

Combination of anti-angiogenic therapy Apatinib and immune therapy potentiate tumor microenvironment

Tumor immune therapy, especially anti-programmed cell death ligand-1/programmed cell death-1 (PD-L1/PD-1) treatment, is currently the focus of substantial attention. However, despite its enormous successes, the overall response rate of cancer immunotherapy remains suboptimal. There is an increased interest in combining PD-L1/PD-1 treatment with anti-angiogenic drug Apatinib to enhance antitumor effect. Presently available data seem to suggest that Apatinib may exert immune suppressive effects to make the PD-L1/PD-1 treatment works. Here, we review the extensive tumor microenvironment immune modulatory effects from antiangiogenic agents Apatinib in order to supporting VEGFR2 targettherapies in clinical trials are existing.

Inflammaging in skin and intrinsic underlying factors

Aging of organs starts from the time of birth and continues throughout life. Aging of skin can be divided into two distinct types—intrinsic aging and extrinsic, based on the fact that the skin is the outermost organ exposed to the external environment. However, despite their different histological features and triggers, intrinsic and extrinsic aging share common biochemical mechanisms. β-galactosidase, p16INK4a, and senescence-associated secretory phenotype (SASP) factors are detected in skin cells as biomarkers of senescence. In particular, inflammatory cytokines, the constituents of SASP, play pivotal roles in “inflammaging” which is a concept involving the relationship between aging and low-grade inflammation. In this review, the features of skin aging and its underlying mechanism of skin aging are summarized.

Acute colonic pseudo-obstruction following nivolumab and ipilimumab combination therapy for metastatic melanoma

Immune-related adverse events (irAEs) are commonly observed in patients treated with immune checkpoint inhibitors (ICI), and prompt diagnosis and treatment of irAEs is of utmost importance. Gastrointestinal (GI) events are among the most frequent irAEs and the hallmark symptom is diarrhea. Intestinal hypomotility as irAEs is exceedingly rare, and needs wider recognition given that the presentation is insidious.Here, we report a case of 79-year-old woman with metastatic melanoma under nivolumab and ipilimumab combination therapy. She developed ileus symptom, and was diagnosed with acute colonic pseudo-obstruction. The symptom relieved soon after administering high-dose prednisolone five days after the onset. ICI therapy was discontinued.Intestinal hypomotility as GI irAEs is exceedingly rare and there have been five reported cases to our knowledge. In reviewing past cases, we speculate that the prompt initiation of corticosteroids resulted in a favorable outcome. Our case illustrates that early recognition of these rare irAEs is essential in order to ensure prompt treatment.

Allogeneic bone marrow transplantation possibly induces a localized type of porokeratosis

A 15-year-old girl underwent allogenic bone marrow transplantation for neuroblastoma. A few years later, she noticed a round lesion on her left buttock. Since the lesion had been asymptomatic and never grown, more than 20 years had passed before she saw a local doctor to consult about it. Although the lesion was suspected to be tinea corporis, no fungi were found on microscopic examination. Subsequently, administered topical corticosteroids were not effective. She was referred to our hospital for further evaluation, and a skin biopsy confirmed the diagnosis of porokeratosis. There was a possibility that chemotherapy, total body radiation, or immunosuppressive therapy associated with allogeneic bone marrow transplantation was involved in the development of porokeratosis. Numerous cases of acquired porokeratosis in immunocompromised status have been observed; as for those after allogenic bone marrow transplantation, 12 cases have been reported in the English literature, 4 of which had only one or a few lesions on a limited area of body surface. Our case was relatively uncommon in that the lesion was solitary and comparatively large. In a localized type of porokeratosis, it was suggested that a malignant skin tumor developed earlier than in other types. Careful follow-up for malignant transformation is especially required.