Days Of Chemotherapy Initiation Research Articles

Prognostic Implications of Timing of Immunotherapy in Stage IV Non-Small Cell Lung Cancer.

Currently, the established approach for addressing stage IV non-small cell lung cancer (NSCLC) involves combining chemotherapy with immunotherapy. However, the necessity for molecular analysis prior to commencing immunotherapy often results in a delay in its initiation following the commencement of chemotherapy. Therefore, this study aimed to study the significance of postponing immunotherapy on pertinent patient outcomes. Using the National Cancer Database (NCBD), patients diagnosed with stage IV NSCLC between 2017 and 2018 were screened. Inclusion criteria comprised those treated with multi-agent chemotherapy as the first-line therapy within 30 days of treatment, surviving beyond 2 months of diagnosis, and absence of neuroendocrine pathology. Patients were grouped among those receiving immunotherapy within 30 days of chemotherapy, immunotherapy within 31 - 60 days of chemotherapy, or chemotherapy alone. Clinical characteristics were collected and their correlation with the timing of immunotherapy was evaluated. The impact of delaying immunotherapy on overall survival (OS) was investigated using Kaplan-Meier analysis. Multivariate Cox regression analysis was employed to identify independent prognostic variables associated with OS. Our cohort comprised 99,008 patients with clinical stage IV NSCLC diagnosed between 2017 and 2018, which were distributed in the three treatment groups described above. Patients receiving immunotherapy within 30 days of chemotherapy showed greater OS in contrast to both those subjected to delayed immunotherapy (hazard ratio (HR) = 0.74, 95% confidence interval (CI): 0.64 - 0.87, P = 0.0003). Subsequent multivariate regression analysis showed that postponing immunotherapy, older age, male sex, white race, non-adenocarcinoma histology, higher clinical N stage, use of radiation treatment, and presence of liver metastasis were all associated with worse OS. Introducing immunotherapy within the first 30 days of chemotherapy initiation significantly increases survival in patients with stage IV NSCLC.

Abstract P4-11-33: Continuous glucose monitoring and hyperglycemia during chemotherapy for early-stage breast cancer

Abstract Background: There are a growing number of breast cancer (BC) survivors who are at risk for short and long-term treatment-related toxicities. BC survivors may be at higher risk of developing diabetes mellitus (DM), and chemotherapy may potentiate this risk due to concurrent corticosteroid use. DM is associated with both short and long-term treatment toxicities and worse BC outcomes. The prevalence of hyperglycemia (HG) during chemotherapy for early-stage BC (ESBC), and the association between HG during chemotherapy and treatment-related toxicities is unknown. Methods: We are conducting a single-arm pilot study to evaluate the prevalence of hyperglycemia among patients with ESBC during chemotherapy (NCT04473378). Patients are eligible if ≥18 years old, initiating chemotherapy with corticosteroid use, not receiving systemic steroids except as supportive care for chemotherapy, and known DM is allowed if patients are not treated with insulin. Within 7 days of chemotherapy initiation, the Freestyle Libre Pro (Abbott Diabetes Care) continuous glucose monitoring system is applied to the posterior arm of each participant. Patches are reapplied every 2-3 weeks and worn continuously until chemotherapy completion (duration per regimen). The Freestyle Libre Pro monitors interstitial glucose every 15 minutes via subcutaneous sensor filaments adhered to the skin without a finger prick. Data is downloaded using a wireless scan of the sensor by a reader. The primary endpoints are: 1) the prevalence of HG, defined as the number of participants who have ≥1 glucose value (fasting or non-fasting) of ≥140 mg/dL at any point from chemotherapy initiation to completion; 2) Among participants who develop HG, the proportion of time in which they have HG, measured as the number of hyperglycemic values (glucose value of ≥140 mg/dL) divided by the total number of glucose values recorded in an individual for the duration of chemotherapy. Secondary endpoints include the prevalence of impaired glucose tolerance (hemoglobin A1c [HgbA1c] ≥5.7%) prior to chemotherapy initiation in patients without a history of DM, and changes in glucose biomarkers (HgbA1c, fructosamine, and serum creatinine) during treatment. Results: Between December 2020 and April 2021, 7 patients were enrolled, with evaluable data for 5 patients. At baseline median age was 60 (range, 37-74) and median BMI was 33.0 (range, 24.6-41.6). Chemotherapy regimens were: docetaxel/cyclophosphamide (40%); docetaxel/cyclophosphamide/trastuzumab/pertuzumab (20%); weekly paclitaxel (20%); and paclitaxel followed by doxorubicin/cyclophosphamide (20%). All patients (100%) developed hyperglycemia. Of 18,768 sensor readings (281,265 minutes) the proportion of time participants were hyperglycemic (≥140 mg/dL) during the period of adjuvant/neoadjuvant chemotherapy was 22.1%, and the mean time from first corticosteroid administration to first hyperglycemic episode was 7.6 hours. Of three patients with no history of DM (including one patient with glucose intolerance), the proportion of time spent hyperglycemic (≥140 mg/dL) was 9.9% (range, 1.7-13.8%), and the mean daily glucose was 106.7 mg/dL (SD 10.3). Of the two patients with DM, the proportion of time spent hyperglycemic was 70.2% (range, 67.2-79.5%) and the mean daily glucose was 171.7 mg/dL (SD 3.1). Changes in glucose biomarkers will be presented with the full cohort. Conclusion: Hperglycemia during chemotherapy occurred in 100% of the cohort, including those without a history of DM or glucose intolerance. It is currently unknown if HG during chemotherapy is a modifiable risk factor for short and long-term BC treatment toxicities including neuropathy. Understanding glucose trends in this setting will help determine a successful intervention for HG during chemotherapy which may reduce short and long-term treatment toxicities. Citation Format: Melissa K Accordino, John H Spivack, Sophie Ulene, Erin Honan, Meghna S Trivedi, Katherine D Crew, Erik Harden, Cynthia Law, Dawn L Hershman. Continuous glucose monitoring and hyperglycemia during chemotherapy for early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-33.

Reduced-Intensity Induction with Dasatinib Vs. Hypercvad + 2nd Generation TKIs with MRD-Guided Follow-up Therapy Leads to Comparable Rates of MRD-Negative Remission While Reducing Transfusions and Neutropenia in Ph+ ALL

Reduced-Intensity Induction with Dasatinib Vs. Hypercvad + 2nd Generation TKIs with MRD-Guided Follow-up Therapy Leads to Comparable Rates of MRD-Negative Remission While Reducing Transfusions and Neutropenia in Ph+ ALL

Chemotherapy regimen is associated with venous thromboembolism risk in patients with urothelial tract cancer.

To assess the association of venous thromboembolism (VTE) with different chemotherapy regimens in patients with urothelial tract cancer. We identified patients aged ≥66 years, diagnosed with urothelial tract cancer in the period 1998 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database. The chemotherapy regimens analysed were gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (CarboG). Propensity scores for treatment regimen based on comorbidities, tumour characteristics, age, and year of diagnosis were calculated. VTE rates within 120days of chemotherapy initiation were calculated. VTE risk stratified by chemotherapy regimen was modelled using multivariable logistic regression, adjusting for treatment propensity scores and additional demographic characteristics. Overall survival stratified by VTE and chemotherapy regimen was estimated using Kaplan-Meier methods and the log-rank test. Of 5594 identified patients, a VTE occurred in 13.0%. The VTE rates within 120 days of chemotherapy initiation were 15.3% for GC, 8.7% for MVAC, and 12.0% for CarboG. On multivariable analysis, MVAC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.94) and CarboG (OR 0.71, 95% CI: 0.59-0.85) were associated with lower VTE risk compared with GC. VTE was associated with worse overall survival (P < 0.001). Compared with GC, MVAC and CarboG were associated with a lower rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Additionally, patients with a VTE had worse survival outcomes than those without a VTE. Analysis of the risk of blood clots with different chemotherapy regimens in patients with urothelial tract cancer showed that GC was associated with the highest rate. We also found that blood clots were associated with worse patient outcomes.

Hospitalization and Survival of Medicare Patients Treated With Carboplatin Plus Paclitaxel or Pemetrexed for Metastatic, Nonsquamous, Non–Small Cell Lung Cancer

Chemotherapy is a mainstay treatment of metastatic non-small cell lung cancer. However, little is known about the comparative risk of hospitalization associated with commonly used chemotherapy regimens. To evaluate the real-world association of specific lung cancer chemotherapy regimens with measures of acute hospital care (primary objective) and survival (secondary objective). Retrospective, propensity-matched, cohort study using the Surveillance, Epidemiology, and End Results-Medicare linked data for cancer diagnoses between 2008 and 2013, with follow-up through 2014. Patients were Medicare beneficiaries 66 years of age or older receiving initial chemotherapy for treatment of stage IV, nonsquamous, non-small cell lung cancer. Analyses were performed between September 2017 and April 2018. Receipt of chemotherapy with carboplatin-pemetrexed or carboplatin-paclitaxel, with or without concurrent bevacizumab. The primary outcome was risk of hospitalization within 30 days of chemotherapy initiation. Secondary measures included cumulative 90-day hospitalizations, 90-day mean hospital-free survival time, and overall survival. Of the 3310 eligible patients, 1823 received carboplatin-pemetrexed, and 1487 received carboplatin-paclitaxel. The median age at diagnosis was 73 years (interquartile range, 69-77 years), 1784 patients (53.9%) were men, and 2909 patients (87.9%) were non-Hispanic white. In total, 2182 patients were included in the propensity-matched analysis. The 30-day hospitalization risk was 20.7% (95% CI, 18.3%-23.1%) among patients receiving carboplatin-pemetrexed vs 26.0% (95% CI, 23.4%-28.6%) among patients receiving carboplatin-paclitaxel (5.3% difference; P = .003). The 90-day cumulative hospitalizations did not differ significantly between the 2 treatment groups; however, the 90-day mean hospital-free survival time was improved for patients receiving carboplatin-pemetrexed (68.4 days [95% CI, 66.5-70.4 days] vs 63.6 days [95% CI, 61.6-65.7 days]; P = .001). The median survival time was 9.0 months (95% CI, 8.4-9.5 months) with carboplatin-pemetrexed therapy vs 7.6 months (95% CI, 7.0-8.4 months) with carboplatin-paclitaxel therapy (P = .005). Stratified analyses showed no association of bevacizumab use with hospitalization risk or survival when combined with either chemotherapy regimen. The findings from this study suggest that patients receiving carboplatin-pemetrexed compared with those receiving carboplatin-paclitaxel have a lower 30-day hospitalization risk, a greater 90-day hospital-free survival, and improved overall survival. Information about hospitalization risk may provide valuable context for evaluating real-world cancer treatment outcomes.

Novel Risk Factors for Predicting the Development of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Undergoing Induction and Re-Induction Chemotherapy

BACKGROUNDInvasive fungal infections (IFI) occur in 5% to 40% of patients with hematologic malignancies, most commonly in patients with acute myeloid leukemia (AML). Historically, at the University of Virginia (UVA), antifungal prophylaxis was not routinely used in patient undergoing induction chemotherapy for AML. With an antifungal treatment naïve patient cohort, this study had the unique opportunity to examine if specific patient characteristics, comorbidities, or diagnostic criteria were predictive for the development of an IFI. METHODSA retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of probable or biopsy proven IFIs within ninety days of chemotherapy initiation as characterized by the European Organization for Research and Treatment of Cancer/Invasive Fungal Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group criteria. Secondary endpoints include patient comorbidity and disease specific indices associated with IFI. Each induction or re-induction regimen was counted as a distinct event. Statistical methods include pairwise Wilcoxon tests, univariate analyses, and Kruskal-Wallis tests. Statistical significance was defined as a p-value <0.05. RESULTSOf 126 patients, there were a total of 176 distinct induction or re-induction events. Thirty-eight patient events (22%) received antifungal prophylaxis with fluconazole per attending physician preference. In patients (n=102, 81%) who did not receive antifungal prophylaxis during induction, there were a total of 19 (19%) patients with probable/proven IFI. There was a significant association with probable/proven IFI in regards to decreased bone marrow cellularity (p-value 0.018). There were no correlations between probable/proven IFI and body mass index, age of diagnosis, gender, nicotine abuse, length of neutropenia, cytogenetics, and bone marrow blast percentage. In the antifungal prophylaxis cohort, 3 patients (8%) had probable/proven IFI.Another aspect reviewed is the potential concept of an immune reserve ratio (IRR). The IRR is the percentage of the bone marrow core cellularity divided by blasts - representing the bone marrow functionality at the time of leukemia diagnosis or relapse. IRR was 1.9 vs 1.4 vs 1.2 (p-value 0.038) for none vs possible vs probable/proven IFI cohorts. DISCUSSIONThis study reveals that decreased bone marrow cellularity and decreased IRR may be used to predict which AML patients undergoing induction chemotherapy are at higher risk of developing an IFI. Traditional risk factors, such as tobacco use, length and degree of neutropenia, were not found to be significant in this review. Other patient co-morbidities, such as hypertension, COPD, and chronic kidney disease, and AML disease specific characteristics, such as cytogenetic and bone marrow blasts, also did not demonstrate clinical significance.To date, studies have not developed a method to quantify a patient's immune reserve at the time of AML diagnosis and risk of IFI. The IRR attempts to use the ratio of bone marrow cellularity and blasts as a surrogate marker of functional immune activity. This review suggests that the IRR is highly correlative of IFI development. Future studies need to be performed to validate this prospectively. UVA is currently conducting a prospective clinical trial examining the utility of IRR to predict IFI in adults with AML induction chemotherapy. DisclosuresNo relevant conflicts of interest to declare.

Clostridium Difficile Infection in Patients with Acute Myeloid Leukemia

BACKGROUNDClostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea and has been not well studied in patients with neutropenia who have hematologic malignancies in the United States. Previous studies suggest patients undergoing induction chemotherapy for acute myeloid leukemia (AML) are at a high risk of contracting CDI, but these patient's clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML patients at the University of Virginia (UVA). METHODSA retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of CDI within ninety days of chemotherapy initiation. CDI was defined by a Clostridium difficile positive PCR in the presence of diarrhea. Secondary endpoints include patient characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon test, Fisher’s exact test, and Holm’s sequential Bonferroni procedure as appropriate. Statistical significance was defined as p-value <0.05. RESULTSOf 126 patients, 31 patients (24.6%) with AML had CDI. 8 patients (25.8%) had one recurrent episode of CDI, 2 patients (6.4%) had two recurrences, and 2 patients (6.4%) had more than two recurrences. 25 patients (80.6%) underwent CT abdominal imaging specifically for the CDI episode, revealing 2 patients (8%) with typhilitis. 2 patients (6.4%) developed toxic megacolon, but no patients underwent colectomy. There was no CDI specific mortality in these 31 patients. During the same 4 year timespan, an additional 27 patients with hematologic malignancies other than AML were identified. These two cohorts (AML and non-AML CDI patients) were not statistically different in terms of patient demographics (age, gender, BMI), medical comorbidities (tobacco use, asthma, COPD, cardiac disorders, CKD, and rheumatologic conditions), and CDI characteristics (recurrences, prior antibiotics prophylactic and treatment regimens, PPI medication usage, CDI treatment regimen and treatment duration, development of typhilitis and toxic megacolon, and mortality). The only statistically significant difference is the presence and increased duration of neutropenia in the AML CDI patient cohort (p-value < 0.001). DISCUSSIONThe study concludes that the incidence of CDI in patients with AML undergoing induction chemotherapy is greater than hospitalized patients without AML as reported in the literature. However, when compared to a matched cohort of hospitalized patients with non-AML hematologic malignancies, the incidence of CDI is similar between these two groups. This result is striking as AML induction chemotherapy regimens are typically more intense, resulting in more profound and longer neutropenia. Even with increased cytopenias, the CDI rate and disease characteristics are not affected when AML CDI patients are compared to non-AML CDI patients. This suggests that cytopenias should not be the focus for CDI patients, rather hematologic malignancies as whole lead to increased CDIs and heightened awareness is warranted when caring for patients with hematologic malignancies and complaints of diarrhea. Patients in both AML and non-AML CDI cohorts have relatively favorable outcome, with no patient mortality attributable to CDI. Further studies are needed to evaluate what, if any, predictive risk factors can increase CDI in the setting of AML. DisclosuresNo relevant conflicts of interest to declare.

An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour.

Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment.

Retrospective analysis of the microbiological spectrum of pneumonia in Turkish patients with lung cancer.

Aim of the studyThe spectrum of pulmonary infections in patients with lung cancer is wide, and tools for target-oriented infection control measures are necessary. In this retrospective study we report the microbiological spectrum of pneumonia (based on the results of sputum culture) in a case series of Turkish patients with lung malignancies.Material and methodsBetween 2010 and 2011 a total of 119 patients (111 males and 8 females, mean age: 59.8 ±9.6 years) with lung cancer and pneumonia were identified at the Department of Medical Oncology of two Turkish Universities (Uludag University, Bursa and Cumhuriyet University, Sivas). Expectorated sputum samples were collected in sterile specimen containers and processed immediately in the hospital bacteriology laboratory.ResultsOf the 119 study patients, 92 (77.3%) had positive isolates from sputum cultures. The most frequent isolate from the sputum of lung cancer patients with pneumonia was Aspergillus fumigatus (n = 22), followed by Haemophilus influenzae (n = 13) and Pseudomonas aeruginosa (n = 12). The likelihood of having a positive Aspergillus fumigatus sputum culture was significantly and independently associated with febrile neutropaenia (OR = 1.32, 95% CI: 1.17–3.68, p < 0.05) and the development of pneumonia within the first 10 days of chemotherapy initiation (OR = 1.78, 95% CI: 1.37–4.12, p < 0.01).ConclusionsWe conclude that Aspergillus fumigatus was the most frequent isolate, but the high diversity of pathogens clearly challenges the empirical use of antimicrobial drugs.

Risk of Febrile Neutropenia (FN) in Select Myelosuppressive Chemotherapy Regimens

IntroductionFebrile neutropenia (FN) is a serious adverse effect of myelosuppressive chemotherapy, which often results in hospitalization and chemotherapy dose modification. FN risk depends on patient characteristics and chemotherapy regimen risk. Understanding the FN risk associated with individual chemotherapy regimens can help guide the use of prophylactic granulocyte colony-stimulating factor (G-CSF) and patient monitoring. To this end, the NCCN has classified regimens into high (≥20%), intermediate (10%-20%), or low (<10%) FN risk based primarily on clinical trial data. However, even for the same regimen, the FN risk is often higher in clinical practice than in clinical trials. In this study, we assessed the FN risk associated with several regimens for which FN risk has not been determined or has shown substantial variability outside of a clinical trial setting, using data from Kaiser Permanente Southern California (KPSC), a large, community-based practice.MethodsIncluded were patients diagnosed with incident non-Hodgkin's lymphoma (NHL), breast cancer (BC), or multiple myeloma (MM) between 2008 and 2013 at KPSC who initiated the following chemotherapy regimens: bendamustine ± rituximab for NHL; docetaxel, carboplatin, and trastuzumab (TCH) or docetaxel and cyclophosphamide (TC) for BC; or Q4W lenalidomide 25 mg/dexamethasone for MM. Bendamustine ± rituximab, TCH, and lenalidomide are not classified by NCCN; TC is classified as intermediate FN risk but has shown considerable variability of FN incidence when used in clinical practice. Data on cancer diagnosis, chemotherapy use, G-CSF use, neutrophil count, and infections were obtained from KPSC's electronic medical records to estimate the incidence proportions of FN and grade 3 and 4 neutropenia. FN was defined as (1) hospitalization with absolute neutrophil count (ANC) <1000/µL or (2) hospitalization with primary or secondary diagnosis codes of neutropenia (ICD-9 288.0x) and fever (ICD-9 780.6), diagnosis code for bacterial/fungal infection, or antibiotic use. Grade 3 neutropenia was defined as ANC ≥500/µL to <1000/µL; grade 4 neutropenia as ANC <500/µL. Patients who received prophylactic G-CSF within 5 days of chemotherapy initiation were excluded from analysis.ResultsOverall, 40 (12%) NHL patients; 149 (24%) and 340 (28%) BC patients who received TCH and TC, respectively; and 0 (0%) MM patients were excluded due to prophylactic G-CSF. Over the first 6 cycles of bendamustine (median 338.4 mg/m2) ± rituximab for NHL patients (n = 307), 7.2% experienced FN, 4.2% grade 3 neutropenia, and 17.6% grade 4 neutropenia. Over the first 6 cycles of TCH for BC patients (n = 462), 24.2% experienced FN, 10.6% grade 3 neutropenia, and 44.6% grade 4 neutropenia. Over the first 6 cycles of TC for BC patients (n = 859), 20.5% experienced FN, 9.5% grade 3 neutropenia, and 37.5% grade 4 neutropenia. Over the first 4 cycles of lenalidomide/dexamethasone for MM patients (n = 186), 3.8% experienced FN, 5.9% grade 3 neutropenia, and 18.3% grade 4 neutropenia (Table 1).ConclusionsUsing NCCN criteria, bendamustine ± rituximab for NHL and lenalidomide/dexamethasone for MM would be classified as low-FN-risk regimens (<10%). By contrast, BC regimens TCH and TC would be classified as high-FN-risk regimens (>20%) based on our data. These results could help inform prophylactic G-CSF use for the selected regimens in clinical practice.Table 1Number and Incidence Proportion of Neutropenic Outcomes Overall and by CycleCancer: RegimenCyclePatients nFN Events n (%)Grade 3 Neutropenia Events n (%)Grade 4 Neutropenia Events n (%)NHL: Bendamustine ± rituximabOverall30722 (7.2)13 (4.2)54 (17.6)130712 (3.9)5 (1.6)28 (9.1)22253 (1.3)4 (1.8)21 (9.3)31732 (1.2)4 (2.3)15 (8.7)41302 (1.5)4 (3.1)10 (7.7)5924 (4.4)4 (4.4)8 (8.7)6692 (2.9)2 (2.9)0 (0)BC: TCHOverall462112 (24.2)49 (10.6)206 (44.6)146270 (15.2)39 (8.4)138 (29.9)232613 (4.0)15 (4.6)42 (12.9)328217 (6.0)9 (3.2)39 (13.8)42476 (2.4)8 (3.2)31 (12.6)51994 (2.0)6 (3.0)25 (12.6)61698 (4.7)3 (1.8)12 (7.1)BC: TCOverall859176 (20.5)82 (9.5)322 (37.5)1859126 (14.7)51 (5.9)266 (30.9)264921 (3.2)42 (6.5)82 (12.6)357119 (3.3)23 (4.0)62 (10.9)451114 (2.7)22 (4.3)45 (8.8)5941 (1.1)3 (3.2)9 (9.6)6842 (2.4)1 (1.2)2 (2.4)MM: Lenalidomide / dexamethasoneOverall1867 (3.8)11 (5.9)34 (18.3)11862 (1.1)8 (4.3)17 (9.1)21013 (3.0)5 (5.0)14 (13.9)3632 (3.2)2 (3.2)8 (12.7)4370 (0)0 (0)4 (10.8) DisclosuresFamily:Amgen Inc.: Research Funding. Klippel:Amgen Inc.: Employment, Equity Ownership. Li:Amgen Inc.: Employment, Equity Ownership. Page:Amgen Inc.: Employment, Equity Ownership.

Body Mass Index Is a Prognostic Factor in Adults with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Multi-Institutional Study in Japan

Background: The prevalence of obesity has more than doubled between 1980 and 2014, worldwide. In Japan, 25% of adults aged ≥20 years (29 % of males and 20% of females) were overweight in 2013. Body mass index (BMI) assesses the proportion of weight versus height, and is commonly used to stratify underweight, normal, overweight, and obesity in adults. However, the prognostic impact of BMI in acute myeloid leukemia (AML) is debatable. In this retrospective study, we aimed to assess whether BMI was associated with clinical outcomes in AML patients in Japan.Patients and Methods: We identified 374 patients with newly diagnosed AML who had been administered either daunorubicin or idarubicin in combination with cytarabine as induction chemotherapy at any of the seven Japanese hospitals that collaborate to form the Yokohama City University Hematology Group from January 2000 to March 2015. Patients with acute promyelocytic leukemia were excluded from this study. BMI is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2). All patients were categorized in one of two groups according to their BMI: underweight (BMI <18.5) and normal weight (BMI, 18.5-24.9) designed as NW, and overweight (BMI, 25.0-29.9) and obese (BMI ≥30.0) designed as OW. We analyzed complete remission (CR) rate, primary induction failure (PIF) which was defined as not achieving CR in two cycles of chemotherapy, and overall survival (OS) in each group.Results: This study included 227 males and 147 females, with median age at diagnosis of 49 years (range, 15-77 years). In BMI classification, 273 were NW (47, underweight; 226, normal weight), 101 were OW (83, overweight; 18, obese). Median BMI was 22.4 (range, 15.9-39). There were not significant differences in age, sex, Performance status (PS), cytogenetic risk, and comorbidities such as diabetes, hypertension, and ischemic heart disease requiring treatment on diagnosis of AML in the two BMI groups. In this cohort, 283 patients (75.7%) achieved CR and 81 (21.7%) experienced PIF, and 10 subjects (2.8%) had an early death (ED) as death occurring within 30 days of chemotherapy initiation. Only one patient received reduced intensity of chemotherapy ( ≥20%) because of obesity. Relapse during the first CR occurred in 173 subjects (46.3%), and death occurred in 139 patients (37.2%). There was no significant difference in CR rate between the NW and OW groups (73.3% and 82%, respectively, P = 0.079). All 10 patients who experienced ED were in NW (3.7%, P = 0.0068). Causes of ED were as follows: infection in 5 subjects; 3 from cerebral bleeding; and 2 deaths from alveolar bleeding. With a median follow-up of 42 months (1-176 months), OS was 52.4% and 64% at 3 years for the NW and OW groups, respectively (P = 0.022; Figure 1). There was no significant difference in PIF and adverse event between theNW and OW groups. Multivariate analysis showed that a better OS was associated with OW (HR 0.65, 95% CI 0.43-0.97, P = 0.033) and the other prognostic factors of age, sex, PS, and cytogenetic risk.Conclusions: The results of this study show that AML patients with BMI ≥25 had better survival. There was no difference in the toxicity of chemotherapy between the different BMI groups. Out study suggests that Increased BMI should not be a criterion for reducing the dose of chemotherapy administered to patients of newly diagnosed AML. [Display omitted] DisclosuresFujita:Chugai Pharmaceutical CO.,LTD.: Honoraria.

Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL). Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors. A total of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4-9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0-11.8; P < .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patient's clinical course, including a VF at diagnosis.

Patient-Reported Outcome Coordinator Did Not Improve Quality of Life Assessment Response Rates: A Report from the Children's Oncology Group.

PurposeHealth related quality of life (HRQL) assessments during therapy for pediatric cancer provide valuable information to better understand the patient experience. Our objective was to determine the impact of a patient-reported outcome (PRO) coordinator on HRQL questionnaire completion rates during a pediatric acute myeloid leukemia (AML) trial.MethodsAAML1031 is a multicenter Children’s Oncology Group therapeutic trial for de novo AML with a secondary aim to assess HRQL of children and adolescents treated with chemotherapy and hematopoietic stem cell transplantation (HSCT). Parents/guardians are the primary respondents and four questionnaires are administered at eight time points. The questionnaires are the PedsQL 4.0 Generic Core Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale, and the Pediatric Inventory for Parents. To improve response rates, a central PRO coordinator was instituted and reminded sites about upcoming and delinquent questionnaires. The proportion of HRQL questionnaires completed were compared prior to, and following institution of the PRO coordinator. This analysis evaluated the first five assessment time points.ResultsThere were231 families who consented to participate in the HRQL aim. Overall response rates for all questionnaires were 73–83%. At time point 1, within 14 days of chemotherapy initiation, post-PRO coordinator completion rates were significantly higher for three of four questionnaires. However, the effect was not sustained and at time point 4, one month following last chemotherapy or HSCT, completion rates were significantly lower post-PRO coordinator for all four questionnaires.ConclusionAddition of a central PRO coordinator did not result in sustained improvement in HRQL questionnaire completion rates. Efforts to improve response rates must consider other strategies.

Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma

Purpose:Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.Patients and methodsCirculating biomarkers of cell death (nucleosomal DNA (nDNA) and cytokeratin 18 (CK18)), and circulating FLT3 ligand, a potential biomarker of myelosuppression, were assessed before and serially after standard chemotherapy in 49 patients with Hodgkin and non-Hodgkin lymphoma. Cytokeratin 18 is not expressed in lymphoma cells so is a potential biomarker of epithelial toxicity in this setting. Tumour response was assessed before and after completion of chemotherapy by 2D and 3D computed tomography radiological response.Results:Baseline nDNA level was significantly higher in all lymphoma subtypes compared with 61 healthy controls and was prognostic for progression-free survival in diffuse large B-cell lymphoma (DLBCL). Decreases in nDNA levels were observed in the first week after chemotherapy; in FL, early falls in nDNA predicted for long remission following therapy. In DLBCL, elevations in nDNA occurred in cases with progressive disease. Circulating CK18 increased within 48 h of chemotherapy and was significantly higher in patients experiencing epithelial toxicity graded >3 by Common Terminology for Classification of Adverse Events criteria. FLT3 ligand was elevated within 3–8 days of chemotherapy initiation and predicted those patients who subsequently developed neutropenic sepsis.Conclusion:These data suggest circulating biomarkers contribute useful information regarding tumour response and toxicity in patients receiving standard chemotherapy and have potential utility in the development of individualised treatment approaches in lymphoma. These biomarkers are now being tested within multicentre phase III trials to progress their qualification.

Evaluation of Low Dose Rasburicase In the Prevention of Renal Insufficiency and Dialysis After Chemotherapy

AbstractAbstract 2574Rasburicase is a recombinant urate oxidase approved for the prevention of tumor lysis syndrome (TLS). In adults, the recommended dose is 0.2 mg/kg intravenously daily up to 5 days. For a 75 kg person, the cost is over $5100. Given the vast reduction of uric acid seen with this dose, it may be possible to use a reduce dose. The aim of this study is to evaluate the effectiveness of 0.1 mg/kg dose vs the recommended dose in the prevention of TLS. Between October of 2003 and February of 2009, all patients with a hematologic or oncologic diagnosis who received rasburicase were reviewed. Rasburicase had been dosed at either 0.1 mg/kg (low dose) or 0.2 mg/kg (standard dose) due to variations in practice among the practitioners. Rasburicase was given on the first day of chemotherapy and repeated as necessary. Renal insufficiency was defined by 0.5 mg/dl rise in serum creatinine (Scr) within 7 days of chemotherapy initiation. The need for dialysis was recorded separately. Labs were performed pretreatment and usually daily after chemotherapy until electrolytes stabilized. A multivariate analysis using pretreatment labs was performed to determine risk factors for renal insufficiency or failure. During the study period, 125 patients received rasburicase. Fifty-five patients received low dose rasburicase and 70 received the standard dose. The diagnoses are listed in Table 1. Lactate dehydrogenase (LDH) was similar between the two groups (604 U/l in low dose vs 665 U/l in standard dose, p = 0.69). Additional doses were required in 14.5% of the low dose patients vs 21.4% of the standard dose patients, p = 0.36. Renal insufficiency was noted only in the standard dose patients 7.4% vs 0%, p = 0.04. Rates of dialysis were similar between low dose patients 7.3% vs 17.4% in the standard dose patients, p = 0.10. Dialysis was often initiated for hyperkalemia and hyperphosphatemia. Only 12.5% were started for elevation in Scr. Uric acid reduction was higher in the standard dose patients (90.4 ± 15.8%) as compared with low dose patients (82.0 ± 19.0%, p = 0.01). Pretreatment Scr, uric acid and phosphorus levels were found to be significant variable for dialysis but only uric acid was found to be significant in the multivariate analysis. Pretreatment uric acid was a risk factor for dialysis (p < 0.001) but not for renal insufficiency (p = 0.24). Our results suggest that low dose rasburicase may be as effective as 0.2 mg/kg. While high dose rasburicase was more effective at reducing uric acid, it did not reduce the need for dialysis because dialysis was often needed for hyperkalemia and hyperphosphatemia which rasburicase did not affect. Despite bias, our results suggest low dose rasburicase may be a viable alternative and definitely support further study into its use. The potential savings could be enormous given that it would be $2550 per patient.Table 1Baseline diagnosis of 125 patients with TLSDiagnosisLow doseStandard dose doseDiffuse large B-cell lymphoma1317Chronic lymphocytic leukemia312Multiple myeloma75Non-Hodgkin's lymphoma47Acute myeloid leukemia47Burkitt's lymphoma34T-cell lymphoma43B-cell lymphoma51Solid Tumor15Myelofibrosis32Mantle cell lymphoma31Amyloidosis02Blast crisis in acute leukemia11B-cell lymphoproliferative disorder01Chronic myeloproliferative disorder01Follicular mixed lymphoma01Hodgkin's lymphoma10undifferentiated10Lymphoreticular myeloid malignancy10Post-transplant lymphoproliferative disorder01Splenic marginal cell lymphoma10Waldenstrom macroglobulinemia10Total5570 Disclosure:No relevant conflicts of interest to declare.

Impact of Weekend Admissions on Quality of Care and Outcomes in Patients with Acute Myeloid Leukemia (AML).

Background: Hospital services can be significantly reduced over the weekend. This was associated with higher mortality among patients with serious medical conditions in previous studies. It is unknown whether weekend admissions affect outcomes of AML patients, as delay in treatment or delay in obtainment of procedures (such as triple-lumen catheter [TLC] placement requisite for anthracycline delivery) may occur for weekend admissions. We investigated quality of care and clinical outcomes of newly-diagnosed AML patients treated with induction chemotherapy and hospitalized on weekends vs. weekdays.Methods: We conducted a retrospective review of all AML patients treated with cytarabinebased induction chemotherapy at Cleveland Clinic from 1994–2008. Data on known prognostic factors (age, WBC at diagnosis, cytogenetic risk groups [as defined by CALGB 8461] and AML etiology [de novo vs. secondary AML]) were collected and controlled for in multivariable analyses. Quality measures included time to TLC placement; time to induction chemotherapy (TTI); length of stay (LOS); early death (within 15 days of chemotherapy initiation); and 30-day mortality. Weekend admissions were defined as starting Friday, 5pm through Monday, 12am. Factors associated with quality of care and outcomes were assessed by the routines of linear, categorical, and survival analyses.Results: In all, 422 patients were identified. Median age was 61 years (range:17–81) and 47% were female. Median baseline WBC was 9.9/mcL (range:0.4–550); 4.7% had acute promyelocytic leukemia, and 30% had secondary AML. Cytogenetics risk distribution was: favorable (11.6%); intermediate (41.2%); adverse (24.2%); unknown/no growth (23%). In all, 24.4% (n=103) were admitted on the weekend. The complete remission (CR) rate was 66.6%; Median times to TLC was 2 days (range:0–27); TTI was 2 days (range:0–22); and LOS was 32 days (4–91). Early death rate was 3.1%, and 30-day mortality 10.4%. Compared to younger (<60 years) patients, older patients had higher 30-day mortality (14.7% vs. 5.8%, p=0.003), early death (4.9% vs. 1.1%, p=0.025), TTI rates (2.7 days vs. 2.1 days, p=0.02), but lower CR (62.9% vs. 77.8%, p=0.001) and overall survival (OS) rates (195 vs. 474 days, p<0.0001). In univariate analyses, time to TLC was delayed for weekend vs. weekday admissions (3.8 vs. 2.7 days, p<0.01), as was a trend for LOS (35.9 vs. 33.5 days, p=0.09). Surprisingly, weekend admissions had lower early mortality (0% vs. 4%, p=0.04) and 30-day mortality (3.9 % vs. 12.3%, p=0.02). There was no difference in TTI (2.5 vs. 2.4 days, p=0.6), CR rates (72% vs. 69%, p=0.6), or OS (258 vs. 273 days, p=0.2). In multivariable analysis, only time to TLC remained significantly longer for weekend admissions (p<0.001).Conclusions: Weekend admissions significantly delayed placement of TLC, and possibly LOS, without affecting other quality parameters or patient survival. This is likely due to immediate initiation of peripheral chemotherapy with cytarabine even prior to the placement of TLC for infusion of anthracyclines, and emphasizes the need to start chemotherapy promptly in AML patients.

Efficacy and Safety of an Irinotecan plus Bolus 5-Fluorouracil and L-Leucovorin Regimen for Metastatic Colorectal Cancer in Japanese Patients: Experience in a Single Institution in Japan

Short-term infusion of 5-fluorouracil with leucovorin in combination with irinotecan or oxaliplatin has been considered as standard treatment for metastatic colorectal cancer. However, until infusion of 5-fluorouracil regimens and oxaliplatin was approved for the treatment of metastatic colorectal cancer in Japan early in 2005, combination of irinotecan with bolus 5-fluorouracil/leucovorin had been the standard treatment. This retrospective study evaluates the efficacy and safety of a modified irinotecan with bolus 5-fluorouracil/leucovorin regimen in Japanese colorectal cancer patients. Forty-six patients untreated with chemotherapy for metastatic colorectal cancer received a modified form of the irinotecan with bolus 5-fluorouracil/leucovorin regimen, consisting of intravenous irinotecan (100 mg/m2) and l-leucovorin (10 mg/m2), and then 5-fluorouracil 500 mg/m2 as an intravenous bolus infusion, weekly for 4 weeks, repeated every 6 weeks until progression or unacceptable toxicity. The overall response rate was 48% (95% confidence interval, 34-62%), and 48% of patients had stable disease. Median progression-free survival was 8.3 months and overall survival was 20.3 months. The incidence of grade 3 or 4 toxicity was as follows: neutropenia, 50%; diarrhea, 4%; fatigue, 13%; nausea, 7%; and vomiting, 7%. Neither treatment-related nor all-cause mortality occurred within 60 days of chemotherapy initiation. Despite the limited availability of oxaliplatin, 29 patients received an oxaliplatin-based regimen after progression. A modified irinotecan plus bolus 5-fluorouracil/l-leucovorin regimen was an active and well-tolerated regimen in Japanese patients with advanced colorectal cancer, showing a different toxicity profile from Western patients.