The Comparative Study of Atopic Dermatitis and Chronic Hand Eczema Clinical Course in Adults after Acute Relapse Treatment

Aims: To evaluate Atopic dermatitis (AD) and Chronic hand eczema (CHE) course in adults after discontinuation of acute or sub acute relapse treatment. Study Design: three groups of adult patients that finished standard treatment for relapse of AD and CHE were followed up within 24 weeks of period to check disease severity, itch intensity and skin management effectiveness. Place and Duration of Study Sample: population of Ivano-Frankivsk region of Ukraine September 2015 – May 2021. Methods: 155 patients (51 females and 104 males; age between 20 and 50 years) with AD or CHE were enrolled in the study. The patients were randomized into three study groups depending on diagnosis. SCORAD index was used to assess disease severity, visual analog scale (VAS) was used to assess skin itch intensity. Frequency of disease treatment re-start with topical or systemic anti-inflammatory drugs as well as patients’sintention to ask for a treatment were calculated. Results: Results of our study have shown that cases of new disease worsening occured within nearest 24 weeks after AD and CHE aggravation treatment discontinuation and are quite frequent despite appropriate skin care. Conclusion: part of adult patients continues suffering from skin itch or mild skin lesions within nearest 24 weeks after discontinuation of intensive treatment of AD or CHE relapse. Prescription of antihistamines and/or topical anti-inflammatory treatment in addition to generally recommended skin care with emollients is crucial for patients with new worsening of the disease. Among patients with a new signs of worsening a part would unlikely ask for a new treatment immediately unless this worsening is moderate or severe.

Health Care Utilization Is High Amongst Adults Who Relapse Following Allogeneic Hematopoietic Cell Transplantation

Background: Leukemia relapse is the leading cause of death for patients who undergo allogeneic hematopoietic cell transplantation (HCT). Relapse post-HCT is associated with poor prognosis; however, the in-hospital health care utilization of this population is unknown. Using a cohort of patients who relapsed post-HCT for acute leukemia (AL) and myelodysplastic syndrome (MDS), we describe survival, intensity of health care utilization, and characteristics associated with high resource utilization at the end-of-life (EOL). Methods: Adult patients with AL/MDS who underwent HCT at a large regional referral center with subsequent relapse between 2005 and 2015 were included in this retrospective study. We created a composite score for EOL health care utilization intensity summing the presence of any of the following criteria: death in the hospital, the use of chemotherapy, emergency department (ED), hospitalization, intensive care unit (ICU), intubation, cardiopulmonary resuscitation, or hemodialysis in the last month of life. Higher scores indicate more intense health care use at EOL. Chi-square and t-tests were used to assess differences in the distribution of health care utilization by post-relapse treatment. Log-rank test statistic and Kaplan Meier curves were used to evaluate differences in survival. Multivariable linear regression analysis was used to determine variables (demographic characteristics, advance directives documentation, palliative care referral, time to relapse) associated with EOL health care utilization intensity. Results: 154 patients were included; median age was 55 years (IQR 38-62), 55% were male, 79% had AL. Following relapse, 28% did not undergo any treatment, 50% received chemotherapy only, and 22% received chemotherapy plus cell therapy (either donor lymphocyte infusion (DLI), second HCT, or DLI plus second HCT). With the exception of age, baseline characteristics (gender, race, graft versus host disease, year of treatment) did not significantly differ by post-relapse treatment group. 140 (91%) patients died within two years of relapse; survival differed significantly by post-relapse treatment group (Figure 1). Health care utilization in AL/MDS patients following post-HCT relapse is described in Table 1. Overall utilization was high with 44% visiting the ED at least once (22% >= 2 times), 92% hospitalized (55% >= 2 times; 16% >= 5 times), and 38% using the ICU (median length of stay 5 days; IQR 3-10 days). Utilization was high even among those receiving no additional therapy (Table 1). For those patients who died, the median (range) intensity score for EOL health care use was 2 (0-8). Most (70%) had a marker of high-intensity health care utilization at the EOL or died in hospital. In multivariable analysis, post-relapse chemotherapy plus cell therapy (estimate (95% CI): 1.41 (0.45-2.37) compared to no treatment was associated with more intense EOL health care use; no other variables were associated with intensity of EOL health care use. Conclusions: Health care utilization following post-HCT relapse is associated with receipt of disease-directed therapy, but remains high across all groups despite known poor prognosis. Interventions are needed to minimize non-beneficial treatments and promote goal-concordant EOL care in this seriously ill patient population. Disclosures Muffly: Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding.

The Addition of Sorafenib to Standard AML Treatment Results in a Substantial Reduction in Relapse Risk and Improved Survival. Updated Results from Long-Term Follow-up of the Randomized-Controlled Soraml Trial

Background: The addition of sorafenib to standard induction and consolidation therapy in newly diagnosed patients (pts) ≤60 years (yrs) with acute myeloid leukemia (AML) led to significant prolongation of event-free survival (EFS) and relapse-free survival (RFS) in the randomized placebo-controlled SORAML trial (NCT00893373). After a median follow-up of 3 yrs, a benefit for sorafenib treated pts was observed also in overall survival (OS), but this difference was not significant. Here, we present updated survival data and information on relapse treatment and outcome. Methods: In the SORAML trial, 267 newly diagnosed untreated fit AML pts up to 60 yrs of age and irrespective of FLT3 mutation status received two cycles of induction chemotherapy with DA (daunorubicin 60 mg/m2 days 3-5 plus cytarabine 100 mg/m2 cont. inf. days 1-7), followed by three cycles of high-dose cytarabine consolidation (3 g/m2 b.i.d. days 1, 3, 5). Allogeneic stem cell transplantation (SCT) was scheduled for all intermediate-risk pts in first complete remission (CR) with a sibling donor and for all high-risk pts with a matched related or unrelated donor. At study inclusion, pts were randomized to receive either sorafenib (2x400 mg/day) or placebo as add-on to standard treatment in a double blinded fashion. Study medication was given on days 10-19 of DA I+II, from day 8 of each consolidation until 3 days before the start of the next consolidation and as maintenance for 12 months (mos) after the end of consolidation. The primary endpoint of the trial was EFS. The results after follow-up of 3 yrs were presented at ASH 2014 (Röllig et al., Blood 2014; 124: 6) and fully published (Röllig et al., Lancet Oncol 2015; 16: 1691-9). Here, we present the results after prolonged follow-up. For this analysis, information on remission and survival status, mode and outcome of relapse treatment including SCT were collected for all randomized pts and analyzed by standard statistical methods. Results: Of 267 treated pts, 134 were randomized in the sorafenib arm and 133 in the placebo arm with a resulting CR rate of 60% and 59%, respectively. After a median observation time of 78 mos, the primary study endpoint EFS in the placebo vs sorafenib arm was 9 mos vs 26 mos (HR 0.68, p=0.01) in univariate Kaplan Meier analysis. The beneficial effect of sorafenib on EFS was confirmed in multivariate Cox regression analysis with a HR of 0.61 (p=0.005). Median RFS in the placebo vs sorafenib arms was 22 vs 63 mos, corresponding to a HR of 0.64 (p=0.033). Exploratory analyses were performed in the 70 relapsing pts (40 after placebo vs 30 after sorafenib treatment). Among relapsing pts, 82% vs 73% achieved a second CR. In these two groups, 88% and 87% of pts received a SCT as part of salvage treatment. A lower proportion of pts in the placebo arm received a second SCT as salvage treatment (5% vs 13%). In the context of salvage SCT, the proportion of haploident donors in the placebo and sorafenib group was 3% vs 15% and the incidence of Grade 3/4 GVDH was 17% vs 0%. SCT-related non-relapse mortality (NRM) was similar in both groups, but the cumulative incidence of second relapse (CIR) was higher in the sorafenib group (35% vs 54% after 48 mos). Therefore, median OS from relapse in the placebo vs sorafenib groups were 27 mos vs 10 mos, corresponding to a HR of 1.68 (p=0.098). The projected median OS from randomization is 83 mos in the placebo arm and was not reached for the sorafenib arm, corresponding to a 5-year OS of 52% vs 61% (HR 0.81, p=0.263). Conclusion: Mature follow-up data confirms the antileukemic efficacy of sorafenib in younger AML pts with and without FLT3 mutation. The addition of sorafenib to standard chemotherapy resulted in a significantly longer EFS and clinically relevant 36% risk reduction for relapse or death. Five pts need to be treated (NNT) to prevent one relapse or death at 3 years and six pts at 5 yrs. Exploratory analyses in relapsing pts show that survival after relapse is shorter after sorafenib which might be due to i) a higher rate of second SCTs and a higher incidence of haploidentical SCT despite the lower frequency of severe GVHD, most likely by chance and not explainable by systematic reasons and ii) a lower response to salvage treatment after sorafenib therapy. Despite these observations, primary sorafenib treatment led to an OS benefit with a 19% risk reduction for death which was not statistically significant since this phase II trial was not adequately powered to detect OS differences. Figure Figure. Disclosures Rollig: Bayer: Research Funding; Janssen: Research Funding. Hüttmann: Gilead, Amgen: Other: Travel cost; Bristol-Myers Squibb, Takeda, Celgene, Roche: Honoraria. Giagounidis: Acceleron: Consultancy; Celgene: Consultancy. Mackensen: AMGEN: Research Funding. Hänel: Roche: Honoraria; Novartis: Honoraria. Thiede: Roche: Consultancy; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Agendix: Employment. Schetelig: Sanofi Aventis: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria.