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BACKGROUND: Paronychia and pyogenic granulomas occur in 1050% of patients treated with epidermal growth receptor (EGFR) inhibitors. Supportive therapy for periungual lesions is challenging, since these adverse reactions are prone to torpidity and frequent relapses. AIM: to evaluate the effectiveness of supportive treatment for paronychia and pyogenic granulomas ― dermatologic adverse events of EGFR inhibitors, with a combined cream with betamethasone dipropionate, clotrimazole, gentamicin, and betaxolol solution. MATERIALS AND METHODS: 16 patients with paronychia and pyogenic granulomas associated with EGFR inhibitor therapy were included in a 12-week open-label prospective study. Paronychia and pyogenic granulomas severity assessment was performed with the NCI-CTCAE v. 5.0, a developed 10-point scale. The intensity of pain was assessed with a visual-analogue scale (VAS). The quality of life was assessed with the Dermatology Life Quality Index (DLQI). RESULTS: A significant improvement of all parameters (p 0.05) was evaluated from week 1, indicating the effective reduction of dermatologic adverse event objective and subjective symptoms, improvement of patients quality of life. By the end of the study, 37.5% of patients had complete resolution of lesions, 62.5% of patients had minimal residual erythema. Decrease of pain sensation in the affected periungual folds was observed throughout the study (p 0.05). DLQI score indicated the "small effect" of paronychia and pyogenic granulomas on patients life by the end of the study. CONCLUSIONS: Supportive treatment of paronychia and pyogenic granulomas with a combined cream with betamethasone dipropionate, clotrimazole and gentamicin and a betaxolol 0.25% solution is effective in the management of paronychia and pyogenic granulomas objective and subjective symptoms, has a high tolerability, allows to improve patients quality of life and continue targeted therapy without dose reduction. Long-term maintenance of pain sensation after paronychia and pyogenic granulomas resolution underlines the need for additional treatment options that will improve the effectiveness of pain management.

Supportive treatment plays an important role in oncology nowadays. The main aims of oncologic supportive treatment are management of cancer symptoms and adverse events of cancer treatment. In terms of dermatologic adverse events the most important types of reaction are oral mucositis during radiation therapy, chemotherapy and during hematopoetic stem cell transplantation, palmoplantar syndrome during chemotherapy, palmoplantar skin reaction, acneiform paronychia and pyogenic granulomas during targeted therapy, immune-related dermatologic adverse events during immunotherapy. During recent years, special attention has been paid to low level laser therapy for the prophylaxis and management of cancer therapy dermatologic adverse events. The effects of low level laser therapy may have a beneficial effect on many conditions that play important roles in the pathogenesis of radiation and chemotherapy-induced complications in oncologic patients. Therapeutic effects of low level laser therapy are attributed to the stimulation of adaptive processes and to the increase of nonspecific resistance. The latter develop due to the close interaction of the immune, humoral and nervous systems. When choosing a method for the supportive treatment of cancer therapy adverse events, it is extremely important to establish safety in terms of the tumor process and absence of negative effects on cancer treatment. Effects of low level laser therapy on the proliferative and invasive activity of an existing malignancy remains a matter of debate due to conflicting results from in vitro studies. At the same time, according to the results of numerous clinical studies, the use of this method is assumed to be safe for cancer patients.

Linear atrophy of the skin or striae (striae distensae) is a widespread cosmetic defect that leads to a significant decrease in patients` quality of life. To date, one of the most effective modalities of striae distensae treatment are laser therapy methods. A wealth of clinical experience has been accumulated in the use of ablative laser techniques, namely the carbon dioxide CO2 laser (10600 nm) in the treatment of striae albae. This article presents a review of current literature and a clinical observation of a patient with different types of linear atrophies.

Cancer treatment with chemotherapy, targeted and immunotherapy is associated with a wide spectrum of dermatologic adverse events. Xerosis (dryness) of the skin is the most prevalent skin side effect in oncologic patients, which occurs both during treatment with "classic" chemotherapy drugs and modern cancer drugs, such as targeted therapy and immunotherapy. Despite the high prevalence of this side effect, current approaches to the correction of skin xerosis in cancer patients are very limited. At the same time, in the absence of adequate supportive treatment of xerosis, the formation of persistent fissures, eczematization and secondary infection is observed, which may lead to antitumor therapy regimen modification. Thus, optimization of prophylactic and treatment strategies for xerosis in patients treated with anticancer drugs remain an important interdisciplinary problem. Balneotherapy is a promising method for the correction of skin xerosis due to a complex positive effect on the level of skin hydration, a decrease in the intensity of inflammatory processes, a beneficial effect on the state of the skin barrier function, as well as an increase in antimicrobial protection. Available data on the use of balneotherapy in the supportive treatment of skin xerosis as a dermatological adverse event of anticancer therapy confirms the high efficacy and safety, as well as good tolerability of this method in cancer patients.

When choosing the frst drug for genetically engineered biological therapy (GEBT), the following are taken into account: the psoriasis phenotype, diagnosed PsA or predictors of its development, the presence of comorbid pathology, contraindications, dosing regimen, the rate of onset of the effect, and the ‘survival rate’. With the advent of new classes of GEBT-drugs, the concept of ‘treat to target’ has been formed, in accordance with which the importance of achieving clear or almost clear skin as a goal of psoriasis therapy has been noted, since studies have shown that achieving clear or almost clear skin (PASI 90, 100) correlates with higher indicators of health-related quality of life. The concept is reduced to the long-term prescription of highly effective and safe therapies (methods) with a high level of evidence in medicine (A, B). The evolution of GIBT has led to the emergence of a new class of anti-IL-23 drugs. The article presents data from clinical studies on the effcacy and safety of the use of the interleukin-23 blocker guselcumab. Own clinical cases are presented with a discussion of the choice made in favor of guselcumab as the frst genetically engineered drug.Conclusions. Data from clinical trials on the high effcacy, ‘survival rate’ and safety of guselcumab in patients with psoriasis and psoriatic arthritis allows, including those with comorbid pathology, to consider it as a starting therapy using genetically engineered drugs. The data of our own results of observation allow us to conclude that guselkumab is highly effective in psoriasis of smooth skin, as well as in lesions of the scalp, anogenital area, with involvement of the nail plates in the process, which justifes its appointment as the frst GIBT drug.

Ultraviolet radiation has a proven damaging and carcinogenic effect, while the blue spectrum of visible light has now been proven to contribute to damage to skin cells. Blue light causes an antiproliferative effect associated with oxidative stress, disruption of the permeability of the epidermal barrier, activates inflammation and the appearance of pronounced, prolonged hyperpigmentation. In this regard, when developing photoprotective agents, it is necessary to take into account the damaging effect of blue light. The frst full spectrum photoprotector is TriAsorB, which allows full protection of the skin from photodamage.

Epidermal growth factor receptor inhibitors (EGFR) have a high rate of class-specific dermatologic adverse events. Supportive treatment of dermatologic adverse events decreases their severity, minimizes the need for dose de-escalation / discontinuation of targeted therapy, improves commitment to anticancer treatment and patient’s quality of life. Close interdisciplinary cooperation between oncologists and dermatologists is a key to the successful management of patients treated with EGFR. This article highlights current approaches to classification, concepts of pathogenesis and clinical course of EGFR-associated dermatologic adverse events, current and promising prophylactic and therapeutic strategies to manage these adverse events.

Introduction. BCR-ABL tyrosine kinase inhibitors are currently used to successfully treat chronic myeloid leukemia (CML). Drug therapy is carried out in a continuous daily mode throughout the patient’s life. Treatment with this group of drugs is associated with specific dermatological adverse events (dAE), which can lead to a change in the regimen of effective, vital therapy for CML patients.Purpose. To study the characteristics of dermatological adverse events, the severity and influence on the quality of life of BCR-ABL tyrosine kinase inhibitors.Patients and methods. The observational study included 93 patients. The clinical manifestations of dAE, their severity were evaluated, their photographs and pathomorphological studies of skin biopsy samples were performed, cases of dose reduction or drug withdrawal due to dAE were recorded. The quality of life of patients with dAE was determined based on the assessment of the dermatological index of quality of life.Results. Imatinib therapy was accompanied by a maculopapular rash in 43.3 % of patients, nilotinib caused follicular keratosis in 12.9 % of patients. In 3.2 % of patients, dasatinib caused hyperpigmentation, in 2.2 % of patients lichenoid rashes of the II degree occurred during treatment with bosutinib. Ponatinib treatment was followed by dAE in 9.7 % of patients. All dAE have an impact on the quality of life of patients, but the maculopapular rash and dyskeratotic changes are most pronounced. In a pathomorphological study, these dAE have specific features corresponding to immuno-mediated dermatitis.Conclusions. The most frequent and pronounced dAE that significantly affect the quality of life of patients with CML are a maculopapular rash and dyskeratotic skin changes: psoriasiform and lichenoid dermatitis. Clinical and pathomorphological characteristics of skin reactions make it possible in the future to determine effective methods of supportive therapy for dAE.

Background. The effective treatment of the hand-foot syndrome is a necessary component of the complex treatment of patients receiving antitumor therapy with multikinase inhibitors. Aims. The assessment of a new effective method for the treatment of palm-plantar syndrome in patients receiving multi-kinase inhibitors. Materials and methods. There are 27 patients received antitumor treatment with multi-kinase inhibitors and had clinical manifestations of the hand-foot syndrome (HFS) for observation. The main group (14 patients) used a combination of an alpha-lipoic acid at a dose of 600 mg per day per os and an ointment containing 0.005% calcipotriol and 0.05% betamethasone dipropionate 2 times a day. The control group, included 13 patients, used a combination with a cream containing 10% urea and ointment containing 0.05% betamethasone dipropionate. Results. After a week of treatment, the regression of the skin process was observed in both groups, but it was more evident in the main group: significant differences in severity of erythema, paresthesia, pain and burning sensation, the Dermatological Life Quality Index (DLQI) were observed at this stage of therapy (p < 0.05). After 2 weeks of therapy: a more positive trend in the main group in terms of erythema, paresthesia and burning, but the most significant difference is DLQI – 17.4 in the main group and 22.8 in the control group (p < 0.0001). At the end of the 3rd week of therapy: differences with the main characteristics of erythema, desquamation, paresthesia (p < 0.0008), pain (p < 0.0001), DLQI (p < 0.0001). At the end point of the study (after 4 weeks of therapy), significant differences were found in reducing the symptoms and the main parameters for evaluating the effectiveness of DLQI in patients of the main group with a reliability of p < 0.0001. The high correlation of DLQI was found with erythema, pain, burning, paresthesia and desquamation. Conclusions. The treatment of the hand-foot plantar syndrome combined using alpha-lipoic acid inside and topical therapy in the form of an ointment containing calcipotriol and betamethasone dipropionate, can be recommended for patients receiving targeted therapy with multi-kinaseinhibitors.

Background: Not everyone with CML responds optimally to TKI-therapy, especially those with BCR::ABL1T315I. PF-114 is a 4 th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR::ABL1 isoforms including BCR::ABL1T315I. We present final results of a phase-1 study (NCT02885766). Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic and molecular response criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 subjects (5 with accelerated phase CML, 46 - with chronic CML), 23 males, were studied. Daily doses were 50-600 mg/d given once daily continuously. Median age was 50 y (range, 29-82 y). Median CML duration pre-study was 10 y (range, 0.3-23 y). 16 subjects had BCR::ABL1T315I. 25 subjects received ≥ 3 prior TKIs. Median follow-up was ≥ 31 mo and median exposure, 6 mo (range, 0.4-52). Therapy was ongoing in 7 subjects at study termination. Others discontinued because of progression (n = 20), AEs (n = 2), consent withdrawal (n = 5), entry into another study (n = 3) or other reasons (n = 14). The MTD was 600 mg with the grade-3 psoriasis-like skin AE as the DLT. There were no vascular occlusive events or deviations of ankle-brachial index. Complete haematologic response (CHR) was achieved in 14 of 30 subjects, major cytogenetic response (MCyR) in 15 of 44 subjects, complete cytogenetic response (CCyR) in 11 of 50 subjects and major molecular response (MMR) in 8 of 51 subjects. Median duration of CHR was 12 mo and has not been reached for MCyR, CCyR and MMR. The best safety/efficacy dose was 300 mg/d with 6 of 9 subjects achieving a MCyR, 5, a CCyR and 4, MMR. 5 of 16 subjects with BCR::ABL1T315I responded, including 4 achieving a MCyR, 2, a CCyR and 1, a MMR. 2 of 6 subjects failing ponatinib achieved a CHR. Conclusion: PF-114 was safe and effective in subjects failing ≥ 2 TKIs and those with BCR::ABL1T315I including those failing ponatinib. The PF-114 dose for further study is 300 mg/d. Disclosures Turkina: Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau; Pharmstandart: Speakers Bureau; Novartis Pharma: Speakers Bureau. Vinogradova: Bristol Myers Squibb: Speakers Bureau; Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Pharmstandart: Speakers Bureau. Lomaia: Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Pharmstandard: Honoraria. Chelysheva: Pfizer: Speakers Bureau; Novartis Pharma: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Pharmstandart: Speakers Bureau. Petrova: Pfizer: Speakers Bureau; Novartis Pharma: Speakers Bureau. Cortes: Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sun Pharma: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Baccarani: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ottmann: Fusion: Honoraria; Incyte: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Novartis: Honoraria. Mikhailov: Fusion Pharma: Current Employment. Novikov: Fusion Pharma: Current Employment. Shulgina: Fusion Pharma: Current Employment. Chilov: Fusion Pharma: Current Employment.

Introduction. The modern anti-tumour preparations from the group of multikinase inhibitors exhibit the high clinical effectiveness. Courses of therapy with such medications are indispensable and vitally important for the treatment of the patients presenting with oncological pathology but, unfortunately, happen to give rise to the development of a toxic reaction in the form of рalmar-plantar erythrodysesthesia which not infrequently prevents the completion of the full-scale treatment. The determination of the adequate skin condition is an indispensable component of the combined treatment of the oncological patients. Materials and methods. The present study included 9 patients treated with various preparations from the group of multikinase inhibitors. All of them developed toxic cutaneous reactions in the form of grade II-III palmar-plantar erythrodysesthesia which was corrected with the use of thioctic acid-based preparation at a daily dose of 600 mg given during 14 days in the combination with pharmaphoresis of the cream containing 0.1% of betamethasone valerate. Results. The use of the proposed therapeutic modality resulted in the reduction of the severity of the clinical manifestations of palmar-plantar erythrodysesthesia, such as erythema, infiltration, desquamation, fissures, etc. Simultaneously, the treatment eliminated certain subjective symptoms including pruritus, pain, and paresthesia. Taken together, these effects significantly improved the patients’ condition and allowed the course of antitumour therapy to be totally completed. Conclusion. The patients presenting with palmar-plantar erythrodysesthesia should be managed with the use of multikinase inhibitors in the combination with the oral administration of a thioctic acid-based preparation and local pharmaphoresis of the cream containing 0.1% of betamethasone valerate.

Background: PF-114 is a 4th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR-ABL1 isoforms including BCR-ABL1T315I. We present data from a phase-1 study in patients with chronic or accelerated phase chronic myeloid leukaemia (CML) failing ≥2 TKIs or with BCR-ABL1T315I (NCT02885766) with ≥6 months therapy. Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic, and molecular criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 patients were enrolled. Daily doses were 50 mg (n=3), 100 mg (n=3), 200 mg (n=9), 300 mg (n=11), 400 mg (n=12), 500 mg (n=3), 600 mg (n=6), 750 mg (n=4) given continuously. Median age was 50 years (range, 29-82 years). Median CML duration pre-study was 10 years (range, 0.3-23 years). All patients had baseline ECOG performance scores 0-1. Twelve patients had BCR-ABL1T315I. Patients were heavily pre-treated: 25 received ≥3 prior TKIs; 5 patients with BCR-ABL1T315I received 1 prior TKI. Interim analysis was conducted at follow-up of ≥6 months (cut-off date January 16th 2019). Therapy was ongoing in 17 patients at doses 200 mg (n=4), 300 mg (n=9), 400 mg (n=3) and 600 mg (n=1) with median duration of exposure of 7,4 (range, 4,6-26), 9,2 (range, 7,4-26), 9,2 (range, 8,3-9,2) and 9,2 months. Other patients discontinued because of progression (n=18), adverse events (n=6), consent withdrawal (n=4), participation in another study (n=3) or other reasons (n=3). The MTD was 600 mg with the grade-3 psoriasis-like skin lesions the DLT, which occurred during the first 28 days of treatment. Reversible grade-3 skin toxicity occurred in 11 patients at doses ≥400 mg. There were no other drug-related non-hematologic grade-3 toxicities except 1 grade-3 toxic hepatitis at 400 mg and there were no detectable effects on ankle-brachial index or vascular occlusive events. The best safety/efficacy dose was 300 mg/d with 6 of 11 patients achieving a major cytogenetic response (MCyR) and 4 of them - a major molecular response (MMR). Higher doses were less effective probably because of toxicity-related therapy interruptions and discontinuations. Five of 12 patients with BCR-ABL1T315I responded, 3 of which achieved a complete hematologic response and 4 achieved MCyR. Conclusion: PF-114 was safe and effective in patients with CML failing ≥2 TKIs or with BCR-ABL1T315I. The most effective dose was 300 mg/d. Five of 12 patients with BCR-ABL1T315I responded. A pivotal study is beginning. Disclosures Turkina: Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Lomaia:Novartis: Other: Travel Grant;Lecture fee; Pfizer: Other: Travel Grant. Shukhov:Pfizer: Consultancy; Novartis: Consultancy. Chelysheva:Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Shikhbabaeva:Novartis: Consultancy; Fusion Pharma: Consultancy. Shuvaev:Fusion Pharma: Consultancy; Novartis: Consultancy; Pfize: Honoraria; BMS: Consultancy. Cortes:Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Ottmann:Roche: Honoraria; Pfizer: Honoraria; Fusion Pharma: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Mikhailov:Fusion Pharma: Employment. Novikov:Fusion Pharma: Employment. Shulgina:Fusion Pharma: Employment. Chilov:Fusion Pharma: Consultancy.

Background: PF-114 mesylate is a 4th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCRABL1 isoforms including those with a BCRABL1T315I. We present data from a phase-1 study in subjects with chronic or accelerated phase chronic myeloid leukaemia (CML) failing ≥2 TKIs or who have BCRABL1T315I (NCT02885766). Methods: 3+3 dose-escalation design to determine maximum tolerated dose (MTD) followed by expanded cohorts for doses ≤MTD. The primary objective was to determine the MTD and identify dose-limiting toxicities (DLTs) during cycle 1 (28 days). Secondary objectives included safety and anti-CML activity based on hematological, cytogenetic, and molecular criteria. Adverse events (AEs) were assessed and graded using NCI-CTCAE v4.03. Results: 51 subjects were enrolled as of June 26, 2018. Daily doses were 50 mg (n=3), 100 mg (n=3), 200 mg (n=9), 300 mg (n=11), 400 mg (n=12), 500 mg (n=3), 600 mg (n=6), 750 mg (n=4) given on a continuous QD schedule. Median age was 50 years (range, 29-82 years). Median interval from diagnosis to study-entry was 10 years (range, 0-23 years). Subjects had baseline ECOG performance scores Conclusion: MTD of PF-114 is 600 mg with skin toxicity as the DLT. The best safety/efficacy ratio was seen at doses of 200 and 300 mg which are being studied in expanded cohorts and soon in a phase-2 study. Disclosures Turkina: Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations. Shukhov:Novartis: Other: provided consultations and performed lectures ; Bristol Myers Squibb: Other: provided consultations and performed lectures . Chelysheva:Bristol Myers Squibb: Other: provided consultations and performed lectures; Fusion Pharma: Other: provided consultations ; Novartis: Other: provided consultations and performed lectures. Cortes:Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding. Ottmann:Novartis: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Fusion Pharma: Consultancy, Research Funding. Mikhailov:Fusion Pharma: Employment. Novikov:Fusion Pharma: Employment. Shulgina:Fusion Pharma: Employment. Chilov:Fusion Pharma: Employment.