Kate Bendall

Impact of febrile neutropenia on R-CHOP chemotherapy delivery and hospitalizations among patients with diffuse large B-cell lymphoma

PurposeThis analysis from an observational study of clinical practice describes the impact of febrile neutropenia (FN) on chemotherapy delivery and hospitalizations.MethodsAdults with diffuse large B-cell lymphoma (DLBCL) scheduled to receive ≥3 cycles of 2- or 3-weekly CHOP with rituximab (R-CHOP-14/21) were eligible. Primary outcome was incidence of FN.ResultsFN data were available for 409 patients receiving R-CHOP-14 and 702 patients receiving R-CHOP-21. FN incidence was R-CHOP-14, 20% (81/409) and R-CHOP-21, 19% (133/702). Rates of primary prophylaxis with granulocyte-colony stimulating factor were R-CHOP-14, 84% (345/409) and R-CHOP-21, 36% (252/702). A large number of patients experienced their first FN episode in cycle 1 (R-CHOP-14, 24/81 [30%]; R-CHOP-21, 63/133 [47%]). Multiple risk factors (≥2) for FN were more frequent in patients experiencing FN than in patients not experiencing FN (R-CHOP-14, 60/81 [74%] versus 179/328 [55%]; R-CHOP-21, 98/133 [74%] versus 339/569 [60%]). A similar trend was observed for unplanned hospitalizations (R-CHOP-14, 63/81 [78%] versus 68/328 [21%]; R-CHOP-21, 105/133 [79%] versus 100/569 [18%]). Achievement of chemotherapy relative dose intensity ≥90% was lower among patients experiencing FN than in patients not experiencing FN (R-CHOP-14, 30/81 [37%] versus 234/328 [71%]; R-CHOP-21, 83/133 [62%] versus 434/569 [76%]).ConclusionsIn patients with DLBCL treated with R-CHOP-14 or R-CHOP-21, patients with an event of FN were more likely to experience suboptimal chemotherapy delivery and increased incidence of unplanned hospitalizations than those without FN. FN-related hospitalizations are likely to impact chemotherapy delivery and to incur substantial costs.

The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: Findings from clinical practice

Febrile neutropenia (FN) risk-assessment and granulocyte-colony stimulating factor (G-CSF) prophylaxis use in clinical practice was evaluated in patients with diffuse large B-cell lymphoma receiving R-CHOP-21. More G-CSF primary prophylaxis was used in patients assessed as high FN risk, but R-CHOP-21 was associated with substantial myelotoxicity in both high- and low-risk groups. In a multivariate analysis, older age, poor performance status, lower baseline hemoglobin, and lack of G-CSF prophylaxis were significantly associated with occurrence of FN in any cycle. Results highlight the need for improved FN risk-assessment and thorough guideline adherence to further reduce FN and better support chemotherapy delivery.

Impact of Age Group on Febrile Neutropenia Risk Assessment and Management in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP Regimens

UNLABELLED Improving the management of elderly patients with lymphoma is of increasing relevance. One thousand one hundred thirteen patients with diffuse large B-cell lymphoma (DLBCL) received rituximab (R)-CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], and prednisone) in an observational study. Both older and younger patients failed to receive growth factor support in accordance with international guidelines; patients 65 years and older were more susceptible to febrile neutropenia (FN) and its consequences. Better application of guidelines could reduce rates of FN and improve outcomes. BACKGROUND The incidence of diffuse large B-cell lymphoma (DLBCL) is increasing in the elderly population, which is a more challenging population to treat because of comorbidities and enhanced sensitivity to chemotherapy toxicities. This analysis evaluated the impact of age group on assessment of febrile neutropenia (FN) risk, supportive care management, and chemotherapy delivery. METHODS The IMPACT non-Hodgkin lymphoma (NHL) trial was an observational study conducted in Europe and Australia. This analysis included 1113 patients with DLBCL treated with rituximab (R)-CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], and prednisone) every 14 days (n = 409) or every 21 days (n = 704). Outcomes were reported for ages < 65 years and ≥ 65 years. The primary outcome in this analysis was the proportion of patients assessed by investigators as having an overall high (≥ 20%) FN risk who received granulocyte colony-stimulating factor (G-CSF) primary prophylaxis. RESULTS For R-CHOP-14, investigators assessed 78% of younger patients and 80% of older patients with ≥ 20% risk of FN, although 14% of younger and 19% of older high-risk patients did not receive G-CSF primary prophylaxis. For R-CHOP-21, investigators assessed 52% of younger and 71% of older patients with ≥ 20% risk of FN; however, 61% of younger and 47% of older high-risk patients did not receive G-CSF primary prophylaxis. Regardless of chemotherapy regimen, rates of FN and unplanned hospitalization were higher in older patients, and delivery of chemotherapy was poorer. CONCLUSION Adherence to G-CSF guidelines in patients assessed with high FN risk was suboptimal in patients with DLBCL receiving R-CHOP chemotherapy, with substantial proportions of both younger and older patients receiving R-CHOP-21 failing to receive optimal G-CSF support. Better application of guidelines could reduce FN rates and improve outcomes.

Economic costs of chemotherapy-induced febrile neutropenia among patients with non-Hodgkin’s lymphoma in European and Australian clinical practice

BackgroundEconomic implications of chemotherapy-induced febrile neutropenia (FN) in European and Australian clinical practice are largely unknown.MethodsData were obtained from a European (97%) and Australian (3%) observational study of patients with non-Hodgkin’s lymphoma (NHL) receiving CHOP (±rituximab) chemotherapy. For each patient, each cycle of chemotherapy within the course, and each occurrence of FN within cycles, was identified. Patients developing FN in a given cycle (“FN patients”), starting with the first, were matched to those who did not develop FN in that cycle (“comparison patients”), irrespective of subsequent FN events. FN-related healthcare costs (£2010) were tallied for the initial FN event as well as follow-on care and FN events in subsequent cycles.ResultsMean total cost was £5776 (95%CI £4928-£6713) higher for FN patients (n = 295) versus comparison patients, comprising £4051 (£3633-£4485) for the initial event and a difference of £1725 (£978-£2498) in subsequent cycles. Among FN patients requiring inpatient care (76% of all FN patients), mean total cost was higher by £7259 (£6327-£8205), comprising £5281 (£4810-£5774) for the initial hospitalization and a difference of £1978 (£1262-£2801) in subsequent cycles.ConclusionsCost of chemotherapy-induced FN among NHL patients in European and Australian clinical practice is substantial; a sizable percentage is attributable to follow-on care and subsequent FN events.

Importance of granulocyte colony-stimulating factor prophylaxis in therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone given every 14 days for diffuse large B-cell lymphoma in routine clinical practice

1 Department of Haematology, Aalborg Hospital, Aalborg, Denmark, 2 Hematology, Henri Mondor Hospital, Creteil, France, 3 Department of Hematology, Erasmus MC, Rotterdam, The Netherlands, 4 Hematology Department, Hospital del Mar, Barcelona, Spain, 5 Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, 6 Haematology, St George ’ s University of London, London, UK, 7 UO Ematologia 1 – CTMO, Fondazione Policlinico MaRe IRCCS, Milano, Italy, 8 University Hospital, Leuven, Belgium, 9 Institute of Pharmaceutical Medicine, University of Basel, Basel, Switzerland, 10 AMLtd, London, UK and 11 Department of Hematology, University Hospital Essen, Essen, Germany

External validation of a risk model of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma

Abstract Febrile neutropenia (FN) is a common and serious complication of chemotherapy treatment. Clinical risk models may help to identify patients at high risk of FN but must undergo external validation before implementation in medical practice. Therefore, this study externally validated previously published clinical models of FN occurrence during chemotherapy in 240 patients with non-Hodgkin lymphoma by using an independent observational dataset (n = 1829). The models demonstrated predictive ability, and validation criteria for predicting any cycle of FN were partially met but a larger than expected decrease in performance was noted (area under the receiver operating characteristic curve was 0.71 in the validation dataset and 0.83 in the training dataset). Age, weight, baseline white blood cell count and planned chemotherapy parameters were confirmed to predict FN risk. Chemotherapy dose reductions, dose delays and colony-stimulating factor use were confirmed as risk modifiers during treatment. Further work is needed to improve the predictive ability of FN risk models.