Variation of Biophysical Parameters of the Skin with Age, Gender, and Body Region

Background. Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. Objective. The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. Methods. Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. Results. There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. Conclusion. Several biophysical properties of the skin vary among different gender, age groups, and body locations

Impact of obinutuzumab alone and in combination for follicular lymphoma

Maryam Sarraf Yazdy, Bruce D Cheson Division of Hematology-Oncology, Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC, USA Abstract: Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL), this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101) is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL. Keywords: obinutuzumab, follicular lymphoma, MRD, monoclonal antibod

Toxicities and Outcomes of Acalabrutinib-Treated Patients with Chronic Lymphocytic Leukemia: A Retrospective Analysis of Real World Patients

Introduction: Acalabrutinib (acala) is an irreversible, second generation Bruton tyrosine kinase inhibitor (BTKi) approved by the FDA for the treatment of relapsed/refractory (R/R) mantle cell lymphoma, and is in advanced stages of clinical testing for front line (FL) and R/R CLL (Byrd NEJM, Wang NEJM). Ibrutinib (ibr) is a well-established and potent treatment for CLL; however, discontinuation due to intolerance precludes a significant number of patients (pts) in clinical practice from long-term benefit of this targeted therapy (Mato et al Blood 2016, Follows BJH 2017). Acala inhibits BTK more selectively than ibr, and while demonstrating impressive activity, may result in significantly less off-target adverse events (AEs). Although not yet FDA approved, it is being increasingly used in CLL pts with ibr-intolerance or cardiovascular or hematologic comorbidities (atrial fibrillation (AF), hypercoagulable state on long-term anticoagulation, etc.) to potentially avoid ibr-related toxicities. The increasing use of acala in clinical practice provides an opportunity to address various knowledge gaps. Therefore, we conducted a multi-institutional, retrospective analysis in CLL pts treated with acala in the real-world setting. We aimed to report and analyze the main reasons for starting acala, its safety, efficacy, outcome and sequencing. Patients and Methods: This multi-institutional, retrospective analysis included acala-treated CLL pts at 9 US cancer centers. We analyzed and described prior treatments, dosing of acala, discontinuations, toxicities and outcomes. The primary endpoint was progression-free survival (PFS) as predicted by the Kaplan Meier method. Results: 69 CLL pts treated with acala (off clinical trials) were identified. Baseline characteristics are described in Table 1. Median age was 70 years (range 51-89) and 6 (9%) and 63 (91%) pts received acala in the FL and R/R settings, respectively. Of the R/R pts, 49 (78%) had received a prior BTKi, 11 (17%) a phosphoinositide 3-kinase inhibitor (PI3Ki), 14 (22%) venetoclax, 18 (29%) bendamustine, and 17 (27%) fludarabine. Median time from diagnosis of CLL to starting acala was 79.5 months. Most common reasons for choosing acala were prior intolerance to other agents in 47 (68%), disease progression on the prior line of therapy in 19 (28%) and concern for intolerance to other therapies due to age/comorbidities in 9 (13%). Prior intolerance to ibr was the reason for starting acala in 46 (98%) of the intolerant pts; the most common AEs leading to discontinuation of ibr were rash in 10 (22%), AF/flutter in 8 (17%), arthralgia in 8 (17%), bleeding in 6 (13%), infection in 6 (13%) and fatigue in 6 (13%). Almost all pts (99%) started on acala 100 mg orally twice daily, with dose reductions required in 5 (7%). The most common toxicities on acala were fatigue in 9 (13%), infection in 9 (13%), diarrhea/colitis in 7 (10%), nausea/vomiting in 6 (9%), headache in 5 (7%), rash in 5 (7%), bleeding in 2 (3%) and AF/flutter in 1 (1%). The median time from the start of acala to an infection was 3 months. With a median follow-up of 5 months, the acala discontinuation rate was estimated to be 19% (13 pts) with median time to discontinuation of 1 month. The main reason for discontinuation was AEs in 8 pts (12%) (no consistent pattern of AEs), all in R/R pts with median time to discontinuation of 3.5 months; 2 others proceeded to CAR T-cell therapy or allogeneic transplant; 2 died of unrelated causes, 1 from progressive disease off acala. Overall response rate (ORR) was 62% (9% CR, 53% PR, number reported = 66), 50% PR in FL (3/6) and 63% (CR 5%, PR 58%, number reported = 60) in R/R pts. The differences likely reflected small numbers and short follow-up. Median PFS and overall survival were not reached (Figs 1a,b). Conclusion: In this group of largely ibr-intolerant pts, the overall acala discontinuation rate was lower than prior reports from clinical trials, although with relatively short follow up. However, discontinuation rate due to AEs appears to be similar to clinical trial data in an ibr-intolerant pt population (Awan Blood Adv, Rogers ICML 2019). These data demonstrate the need for the results of randomized studies, in order to compare the efficacy and AE profile of acala relative to ibr and other novel agents an

Outcomes Among Classical Hodgkin Lymphoma Patients After an Interim PET Scan: A Real-World Experience.

INTRODUCTION: The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients. PATIENTS AND METHODS: Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed. RESULTS: A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation. CONCLUSION: A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients