Prophylaxis of chemotherapy-induced neutropenia with lipegfilgrastim in patients with lung cancer: final results from the non-interventional study NADIR.

OBJECTIVE: Real-world evidence on the application of the granulocyte colony-stimulating factor lipegfilgrastim for the reduction of chemotherapy-induced neutropenia and febrile neutropenia (FN) is limited. The NADIR study aimed to evaluate effectiveness and safety of lipegfilgrastim as primary or secondary prophylaxis in patients with lung cancer undergoing chemotherapy in routine clinical practice. METHODS: The non-interventional study NADIR (German Clinical Trials Register (DRKS) Number DRKS00005711) enrolled 156 patients with small-cell lung cancer (SCLC) and 145 patients with non-small-cell lung cancer (NSCLC), who received lipegfilgrastim during chemotherapy. Primary endpoint was the incidence of severe neutropenia (CTCAE grade 3/4) and FN. The analysis was stratified for age groups (≤65 years vs. >65 years). RESULTS: Approximately half of the patients were aged >65 years (SCLC 54.5%; NSCLC 46.9%). Intention of antineoplastic treatment was mostly palliative (SCLC 89.1%; NSCLC 73.1%). Patients with high FN risk (SCLC 44.9%; NSCLC 28.3%) mostly received lipegfilgrastim for primary prophylaxis (SCLC 81.4%; NSCLC 70.7%). FN was reported in 1.9% SCLC and 1.4% NSCLC patients. At least one severe neutropenia was documented in 30.1% SCLC and 17.9% NSCLC patients. For NSCLC patients aged >65 years, less severe neutropenia was reported as compared to younger patients (14.7% vs. 20.8%). Lipegfilgrastim-related adverse events were reported in 10.3% SCLC and 7.7% NSCLC patients. CONCLUSION: Lipegfilgrastim in routine clinical practice of patients with lung cancer showed similar effectiveness and safety as compared to the pivotal trial. Interestingly, in older patients severe neutropenia was reported less frequently. While most patients with high FN risk received lipegfilgrastim for primary prophylaxis as recommended, there are still 20-30% of patients at high FN risk without primary prophylaxis who could benefit from better adherence to guidelines.

Prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia with lipegfilgrastim in 2489 cancer patients: final results from the non-interventional study NADIR.

Objectives: The non-interventional study (NIS) NADIR (DRKS00005711) evaluated the effectiveness and safety of prophylaxis with lipegfilgrastim, a glycopegylated granulocyte-colony stimulating factor, in 2500 patients undergoing chemotherapy in routine clinical practice. Primary objective was the incidence of chemotherapy-induced severe neutropenia, febrile neutropenia (FN), and neutropenia-associated complications. Methods: NADIR was a prospective NIS conducted in 201 study centers in Germany. Results: The analysis included 2489 patients. Main tumor types were breast cancer (n = 1198, 48.1%), lung cancer (n = 303, 12.2%), non-Hodgkin lymphoma (NHL; n = 337, 13.5%), and prostate cancer (n = 111, 4.5%). Nine hundred and ten (36.6%) patients were aged ≥65 years (regarded as "elderly" patients). Severe neutropenia (CTCAE grade 3/4) was reported in 26.8% (n = 666) and 25.2% (n = 229) of the total population and elderly patients, respectively. FN was documented in 2.7% (n = 68) of the total population vs 3.0% (n = 27) of elderly patients. Primary prophylaxis with lipegfilgrastim among patients with high risk of FN (>20%) was documented in 83.5% of the total population and 75.1% of elderly patients. Infections (CTCAE grade 3/4) were documented in 99 patients (4.0%) in the total population vs 47 (5.1%) elderly patients. Fatal infections were reported in 14 (0.6%) patients in the total population vs 11 (1.2%) elderly patients. Overall, most frequent lipegfilgrastim-related adverse events (AEs) included bone pain (8.0%), anemia (3.2%), leucocytosis (2.7%), and thrombocytopenia (2.5%). Of the patients, 18.0% had ≥1 documented serious AE; none of the fatal events (2.7%) was lipegfilgrastim-related. Conclusions: Lipegfilgrastim administered to patients with solid tumor/NHL undergoing chemotherapy in routine clinical practice showed similar effectiveness and safety compared to the pivotal trials.

Rituximab maintenance therapy of follicular lymphoma in clinical practice.

Standard of care for patients with symptomatic, advanced-stage follicular lymphoma (FL) is rituximab-containing chemoimmunotherapy followed by rituximab maintenance. This prospective, multicenter, noninterventional study analyzed how efficacy and safety data from randomized controlled trials translate into clinical practice in Germany. Both treatment-naïve and relapsed/refractory patients with FL, who responded to rituximab-containing induction and were scheduled for rituximab maintenance, were observed for 24 months. Effectiveness was measured by response and Kaplan-Meier survival analysis. In addition, treatment patterns of induction and maintenance, as well as adverse events, were documented. The evaluable study population consisted of 310 first-line patients and 173 relapsed/refractory patients, including 116 patients with initial Ann-Arbor stage I/II and 20 patients with FL grade 3B. Regarding first-line induction, a shift from R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to R-bendamustine was observed over time, as well as a decline in radiotherapy. 2-year progression-free survival rates were 88.3% (95% confidence interval [CI] 84.0-92.6) for first-line patients and 76.0% (95% CI: 68.8-83.3) for relapsed/refractory patients. Conversion from partial to complete remission (PR, CR) occurred in 53.4% of analyzed first-line patients with PR, resulting in 69.4% CRs at study end (relapsed/refractory: conversion in 42.9%, final CRs 57.9%). Safety results were consistent with the known safety profile of rituximab in this setting. Both treatment-naïve and relapsed/refractory patients with FL show favorable 2-year PFS rates and improvements in the remission status with postinduction rituximab monotherapy as maintenance and consolidation therapy.

NADIR: A Non-Interventional Study on the Prophylaxis of Chemotherapy-Induced Neutropenia Using Lipegfilgrastim - First Interim Analysis.

BACKGROUND: The non-interventional study (NIS) NADIR was designed to assess the effectiveness and safety of lipegfilgrastim, a novel glycopegylated granulocyte-colony stimulating factor, in reducing the risk of both febrile and severe neutropenia. METHODS: Here, the interim analysis of NIS Nadir performed under real-world conditions at 80 oncology practices across Germany is reported. For a patient to be included, lipegfilgrastim at a subcutaneous single dose of 6 mg had to be administered during at least 1 cycle of the chemotherapy under consideration. RESULTS: The interim analysis included 224 patients. Median patient age was 61.1 years (interquartile range 51.2-70.2 years). Main tumor type was breast cancer followed by lung cancer, and non-Hodgkin's lymphoma (46.0, 13.4, and 10.7%, respectively). When lipegfilgrastim was given as primary prophylaxis, no patient developed febrile neutropenia (FN). 1.3% of patients developed FN when primary prophylaxis was withheld. Only 68.6% of patients undergoing chemotherapy and at high risk (> 20%) of developing FN were treated with lipegfilgrastim during the first cycle, exposing disparity between real-world practices and current treatment guidelines. Lipegfilgrastim was well tolerated. The only grade 3/4 treatment-related adverse event was anemia in 1 patient. CONCLUSION: Lipegfilgrastim was effective and safe when administered for the prevention of chemotherapy-induced neutropenia under real-world conditions.

Composite lymphoma of nodular lymphocyte-predominant and classical Hodgkin lymphoma-Epstein-Barr virus association suggests divergent pathogenesis despite clonal relatedness.

Nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma are considered 2 distinct entities whose co-occurrence in 1 patient is extremely rare. We report a case of nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma concurrently affecting the same lymph nodes in a 48-year-old male patient. Amplification and sequencing of the rearranged immunoglobulin heavy chain genes in tumor cells isolated by laser-assisted microdissection revealed identical variable, diverse and joining segment rearrangements and somatic hypermutation events, demonstrating a clonal relationship between the 2 lymphomas. The Epstein-Barr virus-encoded RNA and latent membrane protein 1 were present in the Hodgkin/Reed-Sternberg cells of the classical Hodgkin lymphoma but not in the tumor cells of the nodular lymphocyte-predominant Hodgkin lymphoma, pointing to a common precursor cell but differences in the early steps of pathogenesis.

First report of a case of meningitis caused by Cryptococcus adeliensis in a patient with acute myeloid leukemia.

Cryptococcus adeliensis is a recently described new fungal species which has been isolated from decaying algae in Terre Adelie, Antarctica. We report the first known case of meningitis caused by C. adeliensis in a patient with acute myeloid leukemia undergoing allogeneic peripheral blood stem cell transplantation.