Contemporary Treatment Patterns and Response in Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) across Five European Countries

The treatment pattern of cutaneous T-cell lymphoma (CTCL) remains diverse and patient-tailored. The objective of this study was to describe the treatment patterns and outcomes in CTCL patients who were refractory or had relapsed (R/R) after a systemic therapy. A retrospective chart review study was conducted at 27 sites in France, Germany, Italy, Spain and the United Kingdom (UK) of patients who received a first course of systemic therapy and relapsed or were refractory. Data were collected longitudinally from diagnosis to first-, second- and third-line therapy. The study included 157 patients, with a median follow-up of 3.2 years. In total, 151 proceeded to second-line and 90 to third-line therapy. In the first line (n = 147), patients were treated with diverse therapies, including single- and multi-agent chemotherapy in 67 (46%), retinoids in 39 (27%), interferon in 31 (21%), ECP in 4 (3%), corticosteroids in 3 (2%) and new biological agents in 3 (2%). In the second line, the use of chemotherapy and retinoids remained similar to the first line, while the use of new biologics increased slightly. In sharp contrast to the first line, combination chemotherapy was extremely diverse. In the third line, the use of chemotherapy remained high and diverse as in the second line. From the time of first R/R, the median PFS was 1.2 years and the median OS was 11.5 years. The presented real-world data on the current treatments used in the management of R/R CTCL in Europe demonstrate the significant heterogeneity of systemic therapies and combination therapies, as expected from the European guidelines.

Immunotherapy for Refractory Autoimmune Encephalitis

Autoimmune encephalitis (AE) is an immune-mediated disease involving the central nervous system, usually caused by antigen-antibody reactions. With the advent of autoantibody-associated diseases, AE has become a hot research frontier in neuroimmunology. The first-line conventional treatments of autoimmune encephalitis consist of steroids, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and second-line therapy includes rituximab. Despite considerable research and expanding clinical experience, current treatments are still ineffective for a significant number of patients. Although there is no clear consensus, clinical trial evidence limited, and the level of evidence for some of the drugs based on single reports, third-line therapy is a viable alternative for refractory encephalitis patients. With the current rapid research progress, a breakthrough in the treatment of AE is critical. This article aims to review the third-line therapy for refractory AE

Metastasiertes Mammakarzinom: CDK4-/6-Inhibitoren halten Einzug in die deutsche Versorgungsroutine

<b>Purpose:</b> Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor-positive, HER2-negative (HR + HER2-) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported. <b>Methods:</b> The PRAEGNANT registry was used to identify advanced HR + HER2- BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed. <b>Results:</b> CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy. <b>Conclusions:</b> In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET.

Real-World Treatment Patterns, Adherence and Healthcare Resource Utilization for Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia Among Veterans in the United States

Introduction: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are the most common types of leukemia in adults in the United States. The US veteran population, predominantly older males, are at high risk for CLL/SLL, especially with prior exposure to Agent Orange or other herbicides during military service. With the increasing availability of novel agents and associated improved survival, there is a need to assess the real-world evidence of CLL/SLL burden in US veterans, as well as the clinical and economic outcomes associated with current treatments. The objective of this retrospective cohort study was to examine the clinical burden, costs and healthcare resource utilization of CLL/SLL in veterans. Methods: Adults who were newly diagnosed with CLL/SLL were identified in the Veteran Health Administration dataset from October 2014 to September 2019. Eligible patients were required to have at least 2 visits with CLL/SLL diagnosis, and continuous enrollment of 6 months pre- and 3 months post-index date, defined by the first diagnosis date. The study population was further required to have at least 1 CLL/SLL treatment on or after the index date. Treatment regimens were identified by line of therapy and categorized mutually exclusively as: bendamustine-based (alone or in combination) therapy, other chemotherapies, ibrutinib, rituximab-monotherapy, or other regimen. Descriptive analyses were conducted to examine patient sociodemographic characteristics, comorbidities, concurrent medications, and treatment patterns including the frequency and duration of each treatment regimen. Adherence was measured by discontinuation and switching rates. Discontinuation was defined as no treatment for 90 days from the last day of supply during the study period. To ensure only patients who prematurely discontinued chemotherapy treatment and not those who completed their treatment cycles are captured, premature discontinuation was defined as a treatment duration of &lt;90 days for bendamustine-based and &lt;120 days for rituximab monotherapy. Costs and healthcare resource utilization were examined by first-, second-, and third-line therapy. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were reported for all-cause and CLL/SLL-related, and calculated as the sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM). Multivariable logistic regression was conducted to examine factors associated with costs, frequency and LOS of hospitalizations. Results: Among the 13,664 veteran patients diagnosed with CLL/SLL, 79% were in watch-and-wait and the final study population consisted of 2,861 patients who received at least 1 line of CLL/SLL therapy (mean duration=465 days). Most patients were elderly (median age =70 years), white (83%), and male (98%). Approximately 39% of veterans had concurrent use of proton pump inhibitors at baseline. Average time to treatment initiation from diagnosis to first-line therapy was 315 days. A total of 770 (26.9%) patients further received second-line therapy (mean duration of treatment=318 days) and 199 (7.0%) patients received third-line therapy (mean duration of treatment=229 days). Ibrutinib was the most common treatment regimen across all lines of therapy (first-line: 39%; second-line: 55%; third-line: 43%) with discontinuation rates at 59.6%, 60.1%, and 55.2% in first-, second-, third-line therapy respectively (Figure 1 and 2). The CLL/SLL-related hospitalization rate was 39% with an average LOS of 7 days. Total PPPM all-cause and CLL/SLL-related costs were $26,709 and $17,233, respectively; these costs were increased by line of therapy. Controlling for patient clinical and demographic covariates, treatment discontinuation and treatment switching were statistically significant predictors of higher inpatient admissions, LOS of hospitalizations, and costs. Conclusions: This real-world data demonstrated significant clinical and economic burden associated with CLL/SLL among the US veterans. Furthermore, the suboptimal adherence, as reported by high treatment discontinuation rates and its impact on increasing costs and healthcare resource use, highlights the real-world unmet needs of CLL/SLL management in the veteran population. Future studies are needed to further understand the long-term outcomes of each treatment regimen. Figure 1 Figure 1. Disclosures Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: Ascentage: Research Funding; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; BieGene, Jansen, Ascentage: Consultancy.

Unconventional radiotherapy to enhance immunotherapy efficacy in bulky tumors: a case report

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors .

Cost-effectiveness of preemptive skin treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer in Japan

Background Clinical management of skin-toxicity associated with the use of anti-Epidermal Growth Factor Receptor (EGFR) antibodies to treat colorectal cancer maintains quality of life of patients with colorectal cancer. Results of clinical trials have recommended the efficacy of prophylactic treatment, but the cost-effectiveness is unclear. This study examined the cost-effectiveness of preventive skin care for skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer from the perspective of the Japanese healthcare payer. Methods The data source was J-STEPP trial, which compared preemptive skin treatment with reactive treatment in third-line panitumumab therapy for KRAS wild type metastatic colorectal cancer in Japan. The costs and effectiveness of preemptive treatment was compared with reactive treatment in a 3-year time horizon using a 4-state partitioned survival analysis. The health outcome was quality-adjusted life-years (QALYs). The costs were 2020 revisions to the drug prices. The robustness of the model was verified by one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA). A 2% annual discount was applied to the expenses and QALYs. Willingness-to-pay (WTP) threshold of 5 million JPY was used. Results Preemptive treatment had incremental effects of 0.0029 QALYs, incremental costs of 5300 JPY (48.6 USD), and incremental cost-effectiveness ratios (ICER) of 1,843,395 JPY (16,912 USD) per QALY. The variability of preemptive and reactive treatment costs for skin-toxicity and the disutility of skin-toxicity had a large impact on ICER. From PSA, the cost-effectiveness rate of preemptive treatment was 75.0%. Conclusions The cost to effectiveness of preemptive treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type mCRC is not high.

Rituximab for treatment of non-infectious and non-malignant orbital inflammatory disease

Purpose To provide a comprehensive review of rituximab use for the treatment of non-infectious/non-malignant orbital inflammation. Methods Review of literature through January 2021. Results Individual data was available for 167 patients with refractory non-infectious/non-malignant orbital inflammation who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (108/149, 72.5%) at a mean of 44.6 months following the diagnosis of orbital inflammation (range = 0 to 360 months; median = 13.7 months). Patients with non-infectious/non-malignant orbital inflammation either received prior treatment with corticosteroids only (27/122, 22.1%), or with one (31/122, 25.4%), two (25/122, 20.5%), or three or more (25/122, 20.5%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (80/144, 55.6%), followed by the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; 51/144, 35.4%). Various other off-label regimens were used infrequently (13/144, 9.0%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with orbital inflammation (146/166, 88.0%). Commonly treated diagnoses included granulomatosis with polyangiitis (99/167, 59.3%), IgG-4 related disease (36/167, 21.6%), and orbital inflammation of indeterminate cause (25/167, 15.0%). No side effects were reported in 83.3% (55/66) of cases. The most common RTX-induced adverse event was an infusion-related temporary exacerbation of orbital disease (4/66, 6.1%), which occurred prior to the routine use of systemic corticosteroids as pre-conditioning. Conclusions Overall, RTX appears to be both efficacious and well-tolerated as second- or third-line therapy for patients with non-infectious/non-malignant orbital inflammation.