Effect of Levofloxacin Prophylaxis on Rates of Febrile Neutropenia in Patients Receiving DA-EPOCH-R Chemotherapy for Aggressive Lymphomas

Introduction: Febrile neutropenia (FN) is a serious potential adverse event of myelosuppressive chemotherapy. Dose-adjusted EPOCH-R (DA-EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, with doses adjusted to induce neutropenia of < 0.5 x 10 9/L) is a chemoimmunotherapy regimen used for aggressive lymphomas including diffuse large B-cell lymphoma, double/triple hit, Burkitt, primary mediastinal, and HIV-associated large cell lymphoma. It is associated with high rates of FN (13-25% of cycles) despite use of prophylactic Septra and granulocyte colony stimulating factor (G-CSF). Fluoroquinolone antibiotics have been used in various hematological malignancies to reduce infection rates while on chemotherapy, but this strategy has never been reported with DA-EPOCH-R. This study was conducted to assess the impact of adding routine Levofloxacin prophylaxis on FN and infection rates in patients receiving DA-EPOCH-R. Methods: This is a combined cohort study comparing the patients who received DA-EPOCH-R for newly diagnosed aggressive lymphoma at the London Regional Cancer Program in London, Ontario, Canada before and after the initiation of routine Levofloxacin prophylaxis in July 2020. The prospective cohort received Levofloxacin 500 mg x 7 days with each cycle starting on cycle day 8 in addition to standard supportive care with Septra and G-CSF. The primary objective was the rate of febrile neutropenia. Secondary objectives included days hospitalized, deaths related to infections, and adverse events secondary to Levofloxacin. Results: Thirty patients who received DA-EPOCH-R in the 5 years preceding the initiation of routine prophylactic Levofloxacin were included in the retrospective cohort. Median age was 58 (range 18-79), 66% were male, and 90% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 110, with a median of 4 cycles per patient (range: 1-6). FN developed in 14 patients (46%), and complicated a total of 20 cycles (18%) of DA-EPOCH-R. There were 19 hospital admissions due to FN, with a median duration of hospitalization of 12 days (range 3-120). Two patients died, both due to infection. Thirteen patients have been treated so far in the prospective cohort, 12 of whom received levofloxacin prophylaxis. Median age was 59 (range 23-69), 66% were male, and 76% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 60, with a median of 5 cycles per patient (range: 1-6 ). Only 1 patient (8%) developed FN, which complicated a total of 3 cycles (5%) of chemotherapy. All 3 episodes of FN resulted in hospitalization for a median duration of 30 days (range 20-49). There have been no deaths due to infection in this cohort thus far. No concerning adverse effects from Levofloxacin have been observed. Conclusions: Although enrollment in the prospective cohort is ongoing, preliminary data are highly encouraging, with significantly lower rates of FN and death due to infection observed since the introduction of routine Levofloxacin prophylaxis. The addition of Levofloxacin to standard prophylaxis with Septra and G-CSF seems to be an effective way to mitigate the risks to patients on DA-EPOCH-R for aggressive lymphomas, and this strategy is worthy of further study. Disclosures Lam: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria.

Prevalence and predictors of pulmonary fungal infections in patients with acute leukemia and aggressive lymphomas: Implications for cancer care in developing countries

Objectives: Among patients receiving cancer therapy, pulmonary fungal infections (PFIs) are an important cause of morbidity and mortality. Identifying predictors of PFI can direct targeted prophylaxis to improve outcomes, especially in low- and middle-income countries (LMIC) with limited resources. The objectives of the study were to evaluate the predictors of PFI in hospitalized patients with hematological malignancies in the United States and implications for prioritizing anti-fungal care in LMIC. Materials and Methods: Using the 2018 National Inpatient Sample, we conducted a retrospective study of patients ≥18 years, with acute leukemia or aggressive lymphoma. Demographics and outcomes were compared between patients with and without PFI. Predictors of PFI were evaluated by regression analysis. Results: PFI was diagnosed in 1635 (0.8%) of 205,525 eligible hospitalizations and aspergillosis was noted in 1315 (80.4%) of PFI cases. Patients with acute myeloid leukemia (AML) accounted for 64.2% of cases of PFI. Patients with PFI, when compared with those without PFI, were younger, had higher Charlson comorbidity index, were more likely to be non-Caucasian, and to have AML. Patients with PFI had higher odds of respiratory failure, sepsis, and in-hospital mortality. Variables associated with PFI were Hispanic or native American origin (OR = 1.71; 95% CI: 1.21–2.42), Charlson comorbidity index ≥3 (OR = 1.52; 95% CI: 1.16–2.00), neutropenia (OR = 1.97; 95% CI: 1.58–2.46), malnutrition (OR = 2.30; 95% CI: 1.75–3.01), bone marrow transplant status (OR = 2.28, 95% CI: 1.53–3.39), and AML diagnosis (OR = 3.12; 95% CI: 2.40–4.05). Conclusions: This study identified variables associated with PFI in patients diagnosed with acute leukemia and aggressive lymphomas. In LMIC, where resources are scarce, patients with cancer who have the identified high-risk characteristics should be given priority for antifungal prophylaxis.

Pulmonary fungal infections in acute leukemias and aggressive lymphomas: Analysis of the United States National Inpatient Database.

e19042 Background: For patients undergoing intensive chemotherapy, pulmonary fungal infections (PFI) represent a major cause of morbidity and mortality. Our study examined predictors and outcomes of PFI in hospitalized patients (pts) with hematological malignancies in the current era of antifungal prophylaxis for high-risk patients. Methods: Using the 2018 National Inpatient Sample (NIS) database, we conducted a retrospective study of hospitalized pts aged ≥ 18 years, with acute leukemias or aggressive lymphomas. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes for leukemias, lymphomas and PFI (candidiasis, aspergillosis, cryptococcus, and mucormycosis). Demographics, comorbidities, and outcomes were compared between pts with and without PFI using Chi-squared test. Multivariable logistic regression was performed to explore predictors associated with PFI. Results: Of 205,525 hospitalizations that met the inclusion criteria, PFI was diagnosed in 1635 (0.8%). Frequent infections were aspergillosis (80%) and candidiasis (11%). Pts with acute myeloid leukemia (AML) accounted for 64% of all PFI. The PFI group, compared to non-PFI, were more likely to be non-Caucasian (39% vs 32%, p<0.05), have higher Charlson comorbidity index (CI) [64% vs 55%, p<0.01], longer mean length of stay (23 vs 9 days, p<0.001), and more likely to have AML (64% vs 33%, p<0.001). Pts with PFI had higher odds of acute respiratory failure, severe sepsis, and in-hospital mortality. Mortality rates for PFI and non-PFI group were 17% and 6% respectively (p<0.001). Predictors associated with PFI were Hispanic or Native American race, Charlson CI ≥ 3, neutropenia, malnutrition, bone marrow transplant status and diagnosis of AML (Table). Conclusions: Our study identified clinical variables that predicted for PFI in patients with acute leukemias and aggressive lymphomas. Pts with these high-risk characteristics should get priority for close surveillance, mold-specific prophylaxis, and antifungal therapeutic drug monitoring. Selected predictors associated with pulmonary fungal infections. Adjusted Odds ratio (OR).[Table: see text]

Strategies for introducing palliative care in the management of relapsed or refractory aggressive lymphomas

Recent advances in treatment of patients with aggressive lymphomas ranging from chimeric antigen receptor T-cell therapy to combination of antibody–drug conjugates with chemotherapy have improved survival outcomes. Despite these significant advances, patients with relapsed or refractory disease experience high physical and psychological symptom burden, and a substantial proportion still die of their lymphoma. In addition, end-of-life care outcomes are suboptimal with high rates of intensive end-of-life health care use and low rates of timely hospice enrollment. Integrating palliative care concurrently with disease-directed care for this patient population has strong potential to improve their symptom burden, quality of life, and end-of-life care. Multiple factors, including heightened prognostic uncertainty in the setting of relapsed/refractory disease, pose challenges to timely provision of palliative care. This article reviews benefits of primary and specialty palliative care for patients with relapsed/refractory aggressive lymphomas and barriers to such care. It also highlights strategies for effectively integrating palliative care for patients with relapsed/refractory aggressive lymphomas.

Quality of Life after Diagnosis in Survivors of Aggressive Lymphomas

Background: Aggressive lymphomas are potentially curable; however, long-term effects of treatment and the disease may adversely affect patients' quality of life (QoL). We investigated QoL at baseline, and up to nine years after diagnosis in survivors of aggressive lymphomas. Methods: Patients newly diagnosed with lymphoma were prospectively enrolled within nine months of diagnosis in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) and systematically followed. Patients were enrolled from September 1, 2002 until June 30, 2015. Eligibility criteria included being a United States resident, English-speaking, no history of HIV, and aged 18 years and older. All pathology was reviewed by a lymphoma hematopathologist. Aggressive lymphoma subtypes included in this analysis were diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma grade III, Hodgkin lymphoma, T-cell lymphoma, other non-Hodgkin lymphoma not otherwise specified (NOS), other B-cell lymphoma NOS, and composite lymphomas. We assessed QoL using the Functional Assessment of Cancer Therapy-General (FACT-G) scale at baseline enrollment, and 1, 2, 3, 6, and 9 years post-diagnosis. FACT-G measures well-being (WB) in four domains-physical (PWB), social/family (SFWB), emotional (EWB), and functional (FWB), which are added to create a total (TOT) score. Those who completed &lt;80% of FACT-G questions at any given time point were excluded. "Survivor" was defined as alive at 1, 2, 3, 6, and 9 year follow-up with no active disease or treatment within six months of a given time point. Because patients could be enrolled at any time within the first 9 months from diagnosis, the timing of initial QoL assessment was variable with respect to the start of lymphoma treatment. We estimated longitudinal change in QoL using mixed models incorporating scores from all available time points. The minimally important difference (MID) of 5 points for TOT and 2 points for each of the domains was used to determine clinical significance. Scores were compared to United States (US) general population normative data. All statistical analyses were performed using SAS (v 9.4). Results: From September 1, 2002 to June 30, 2015, 3,028 patients with aggressive lymphomas were prospectively enrolled in the MER, of which 2,018 completed the FACT-G baseline assessment (47% prior to therapy initiation). Of these patients, 1,144 at 1 year, 1,002 at 2 years, 943 at 3 years, 562 at 6 years, and 289 at 9 years post-diagnosis completed the FACT-G at both baseline and each of the respective time points after diagnosis, and met the definition of survivor. The median age at diagnosis of patients analyzed was 59 years (range 18-93). The cohort included 844 female patients (42%). DLBCL comprised 44% of cases, Hodgkin lymphoma 19%, T-cell lymphoma 11%, composite lymphomas 8%, other B-cell NOS 6%, other non-Hodgkin lymphoma NOS 7%, and Follicular lymphoma grade III 5%. QoL increased from baseline enrollment; the largest increase was seen from baseline to 1 year after diagnosis with a statistically and clinically significant mean TOT score difference of 6.7 points. This mean increase in TOT scores sustained over time with an increase of 7.8 points above baseline at 9 years after diagnosis. At baseline, PWB, EWB, and FWB scores were significantly lower in patients with aggressive lymphomas compared to the US general population, and SFWB scores were significantly higher (all p &lt;0.01); however, only SFWB and EWB score differences were clinically significant as defined by MID. SFWB showed only a mild decline from baseline over the course of 9 years. Despite this, all SFWB scores were statistically and clinically significantly higher than the US general population at 1, 2, 3, 6, and 9 years after diagnosis (all p &lt;0.01 and MID &gt;2). Patients with aggressive lymphomas TOT scores at baseline did not differ from the US general population, while TOT scores at 1, 2, 3, 6, and 9 years post-diagnosis were statistically and clinically significantly higher. Overall, the results in the pre-treatment QoL subset were consistent with the cohort as a whole. Conclusions: In survivors of aggressive lymphomas, QoL improved primarily in the first year after diagnosis, and sustained over the course of nine years. QoL in survivors of aggressive lymphomas is higher than the United States general population at 1, 2, 3, 6, and 9 years after diagnosis. Figure Disclosures Maurer: Pfizer: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Farooq:Kite, a Gilead Company: Honoraria. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding.