Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials.

BACKGROUND: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low-dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real-world evidence is scarce. PATIENTS AND METHODS: POSEIDON was a prospective non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. RESULTS: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression-free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. CONCLUSION: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real-world setting. Registered at clinicaltrials.gov (NCT02075996).

Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis.

OBJECTIVES: Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. METHODS: In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. RESULTS: Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). CONCLUSION: The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

Longitudinal Humoral and Cellular Immune Responses Following SARS-CoV-2 Vaccination in Patients with Myeloid and Lymphoid Neoplasms Compared to a Reference Cohort: Results of a Prospective Trial of the East German Study Group for Hematology and Oncology (OSHO).

Purpose: To assess humoral responses longitudinally and cellular immunogenicity following SARS-CoV-2-vaccination in patients with hematologic and oncologic malignancies receiving checkpoint-inhibitors. Methods: This prospective multicenter trial of the East-German-Study-Group-for-Hematology-and-Oncology, enrolled 398 adults in a two (patients; n = 262) to one (controls; n = 136) ratio. Pre-vaccination, day 35 (d35), and day 120 (d120) blood samples were analyzed for anti-spike antibodies and d120 IL-2+IFNγ+TNFα+-CD4+- and CD8+-cells. Laboratories were blinded for patients and controls. Results: Patients belonged to the myeloid (n = 131), lymphoid (n = 104), and checkpoint-inhibitor (n = 17) cohorts. While d35 seroconversion was higher in controls (98%) compared to patients (68%) (p < 0.001), d120 seroconversion improved across all patient cohorts [checkpoint-inhibitors (81% to 100%), myeloid (82% to 97%), lymphoid (48% to 66%)]. CD4+- and CovCD8+-cells in the lymphoid (71%/31%) and control (74%/42%) cohorts were comparable but fewer in the myeloid cohort (53%, p = 0.003 /24%, p = 0.03). In patients with hematologic malignancies, no correlation between d120 humoral and cellular responses was found. A sizeable fraction of lymphoid patients demonstrated T-cell responses without detectable spike-specific-IgGs. Conclusions: Evidence of vaccine-elicited humoral and/or cellular immunogenicity in most patients is provided. Both humoral and cellular responses are crucial to determine which patients will generate/maintain immunity. The findings have implications on public health policy regarding recommendations for SARS-CoV-2 booster doses.

Venous access ports: frequency and management of complications in oncology patients.

Totally implantable venous access ports have been in use now for over 20 years. They are valuable instruments for long-term intravenous treatment of patients with cancer. Apart from perioperative difficulties, the typical complications associated with venous access ports are venous thrombosis, port infection, extravasation, pinch off syndrome, dislocation, occlusion and catheter leakages. The vast majority of these complications are avoidable, or at least the complication rate can be reduced with health care personnel training and education of patients. This review will give a broad overview on the frequency and possible complications related to port devices. Furthermore, this review suggests strategies for management including proposals to avoid such complications.

Diagnostic work-up for the detection of malnutrition in hospitalized cancer patients.

BACKGROUND: Malnutrition is a common complication in patients suffering from cancer. It is associated with a poor prognosis, reduced quality of life, increased chemotherapy-induced toxicity, and a decreased response to therapy. OBJECTIVE: To evaluate and compare the use of various diagnostic tests for the detection of malnutrition in patients hospitalized for cancer treatment. METHODS: In this single-center, non-interventional reliability study, the nutritional status of 50 patients with cancer was assessed using the Nutritional Risk Screening (NRS-2002), a bioimpedance analysis (BIA), and the measurement of laboratory parameters that reflect the serum visceral protein level. For statistical analysis, the comparison of means and the agreement of the methods were calculated. RESULTS: NRS-2002, BIA, and lab parameters differed widely among patients classified as well-nourished or malnourished (10%- 80%, depending on the method). Significant results in the comparison of means were observed for body mass index, serum protein, and some BIA parameters. The analysis of agreement identified a compelling agreement for pre-albumin and retinol-binding protein (RBP) (kappa = 0.81). LIMITATIONS: Small sample size, heterogeneous group of patients, non-interventional reliability study. CONCLUSION: The tested diagnostic methods for detecting malnutrition did not have an evident agreement among each other with a limited exchangeability. In routine hospital practice several methods should be applied in order to identify cancer patients at risk of malnutrition.

Anthracycline extravasation injuries: management with dexrazoxane.

The application of anthracyclines in anticancer therapy may result in accidental extravasation injury and can be a serious complication of their use. Tissue necrosis with skin ulceration is a possible outcome in the inadvertent extravasation of anthracyclines during intravenous administration. Until recently, there has been no effective treatment against the devastating effect of extravasated anthracycline. Preclinical and clinical studies are leading to the clinical implementation of dexrazoxane as the first and only proven antidote in anthracycline extravasation. In two multicenter studies dexrazoxane has proven to be highly effective in preventing skin necrosis and ulceration. This review focuses on the development and management of dexrazoxane in anthracycline extravasation injuries.

Safety and efficacy of a triple antiemetic combination with the NK-1 antagonist aprepitant in highly and moderately emetogenic multiple-day chemotherapy.

AIM OF THE STUDY: In multiple-day chemotherapy (MDC), the combination of a 5-HT(3)-antagonist plus dexamethasone is still a standard of care. The role of a NK-1-antagonist remains to be defined. PATIENTS AND METHODS: Seventy eight cancer patients undergoing multiple-day chemotherapy of high (HEC) or moderate (MEC) emetic risk received granisetron, dexamethasone plus aprepitant during chemotherapy. After the end of chemotherapy, aprepitant plus dexamethasone was given for another 2 days. Primary end-point was complete response (CR) in the overall phase (day 1 until 5 days after the end of chemotherapy). RESULTS: Thirty eight patients underwent HEC and 40 patients underwent MEC for a median of 3.5 days. CR was seen in 57.9% and 72.5% of patients receiving HEC and MEC, respectively. The tolerability of the aprepitant regimen over 5-7 days was comparable with a 3-day aprepitant regimen. CONCLUSIONS: This is the first report in MDC with a NK-1-antagonist containing antiemetic regimen showing a favourable safety profile with good antiemetic efficacy.

2-(4-(Tetrahydro-2H-pyran-2-yloxy)-undecyl)-propane-1,3-diamminedichloroplatinum(II): a novel platinum compound that overcomes cisplatin resistance and induces apoptosis by mechanisms different from that of cisplatin.

(4-(Tetrahydro-2H-pyran-2-yloxy)R1)R2-diamminedichloroplatinum(II) complexes (1-12) consisting of CDDP linked to THP via aliphatic CH2-spacers were tested in two TGCT cell lines. The most promising compound, 2-(4-(tetrahydro-2H-pyran-2-yloxy)-undecyl)-propane-1,3-diamminedichloroplatinum(II) (12), completely overcame CDDP resistance of 1411HP cells, correlating with increased and accelerated cellular platinum uptake and much faster initiation of apoptotic cell kill. At equitoxic IC90 concentrations, 12 induced accelerated DNA fragmentation and caspase -3 and PARP cleavages. In contrast, DNA platination rate was much lower as compared to CDDP and no upregulation of p53 as well as no initiation of cell cycle arrest were observed. Apoptosis induction by 12 could not be inhibited by pretreatment with caspase-specific inhibitor Z-VAD-Fmk and was accompanied by strong calcium release and generation of reactive oxygen species. To summarize, 12 overcomes CDDP resistance and induces programmed cell death with molecular features different from CDDP, suggesting that both drugs induce apoptosis through different initial pathways.