Rates Of Neutropenia Research Articles

Dose Adjustment of Oxaliplatin Based on Renal Function in Patients With Metastatic Colorectal Cancer.

The effect of renal dysfunction on the toxicity and efficacy of oxaliplatin remains unclear. We investigated the association between creatinine clearance (Ccr), a marker of renal function, and the toxicity and efficacy of oxaliplatin in patients with metastatic colorectal cancer (mCRC). Patients with mCRC who received oxaliplatin-based chemotherapy as first-line treatment were included in this study. Primary outcome was peripheral neuropathy (Grade ≥2), while secondary outcomes included neutropenia (Grade ≥3), thrombocytopenia (Grade ≥2) and overall survival (OS). A total of 145 patients with mCRC were eligible. Incidence rates of peripheral neuropathy (Grade ≥2), neutropenia (Grade ≥3) and thrombocytopenia (Grade ≥2) were 30.3%, 37.2% and 16.6%, respectively, and median OS was 29.1 months. Cox proportional hazards analysis indicated that there was no significant relationship between Ccr and any adverse event, or between Ccr and OS. Dose reduction of oxaliplatin based on Ccr is not recommended in patients with mCRC.

Comparison of Carboplatin Plus Pemetrexed Followed by Maintenance Pemetrexed With Docetaxel Monotherapy in Elderly Patients With Advanced Nonsquamous Non–Small Cell Lung Cancer

Few clinical trials have been specifically designed for elderly patients with advanced non-small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit. To determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC. This open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019. Patients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks. The primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model. Of the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n = 217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n = 216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority = .003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed. Carboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC. University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460.

Evaluation of methotrexate clearance with an enteral urine alkalinization protocol for patients receiving high-dose methotrexate.

High-dose methotrexate is a cytotoxic agent used to treat several malignancies. Urine alkalinization with sodium bicarbonate and hyperhydration are given with methotrexate to prevent drug precipitation in the kidneys. Due to a nationwide intravenous sodium bicarbonate shortage, an enteral-based urine alkalinization protocol was instituted. This study compared outcomes and adverse effects between the previously used intravenous and newly implemented enteral protocols. Single center retrospective cohort study comparing parenteral and enteral urine alkalinization for patients that received methotrexate doses ≥ 500 mg/m2 between 1 April 2016 and 1 October 2018. The primary endpoint was time to methotrexate clearance. Secondary outcomes included length of stay, time to administration of methotrexate, amount of sodium bicarbonate utilized, toxicities of methotrexate, and protocol-associated adverse effects. There were 67 patients included in the study for a total of 195 infusions. The average time to methotrexate clearance between the two cohorts was similar (parenteral 88 h vs. enteral 98 h p = 0.06). Likewise, length of stay was not different between the two cohorts (p = ns). The enteral cohort methotrexate's doses were initiated faster and received significantly less intravenous sodium bicarbonate when compared to the parenteral cohort (p = 0.04). Rates of acute kidney injury, neutropenia, hepatotoxicity, and mucositis were similar between the two groups. There were higher rates of diarrhea and low serum bicarbonate values in the enteral cohort. This study supports the ability to conserve intravenous sodium bicarbonate by using an enteral-based urine alkalization regimen for HD methotrexate, with no difference in outcomes or toxicity.

Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence.

This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.

Clinical pharmacokinetics and drug exposure-toxicity correlation study of docetaxel based chemotherapy in Chinese head and neck cancer patients.

BackgroundArea under time-concentration curve (AUC) of docetaxel is related with its toxicity and efficacy. The aim of this study is to investigate the target range of docetaxel AUC in Chinese head and neck cancer (HNC) patients.MethodsEligible HNC patients were enrolled and received at least 2 cycles of docetaxel-based chemotherapy. A simplified pharmacokinetic (PK) strategy (2 monitored samples) was developed to simulate docetaxel AUC using the nonlinear mixed-effect modelling program. Preliminary target range of AUC was pre-set as 2.5–3.7 µg·hr/mL according to pooled analysis from 8 previous studies. Fisher exact test was used to analyze the relationship between AUC with neutropenia and efficacy, and to verify the target range.ResultsThirty-nine eligible patients were enrolled. Grade 3-4 and grade 4 neutropenia rate in 1st cycle was 64% and 36%, respectively. AUC simulation by simplified PK strategy was acceptable compared to full sampling method from the analysis of archived 300 patients’ data, with −5.67% of mean prediction error (MPE). Median AUC of all patients was 2.58 µg·hr/mL (range from 1.28 to 9.39). A significant correlation (P=0.007) was detected between AUC and body surface area (BSA)-dosage, but BSA contributed only 18.3% of AUC inter-individual variability. Docetaxel AUC was significantly related with the severity (grade 3–4) of neutropenia (correlation of coefficient was 0.452, P=0.004). Fourteen patients (36%) were within the target AUC range. Patients with AUC above the target experienced more severe neutropenia (grade 3–4 rate 100% vs. 56%, P=0.036; grade 4 rate 86% vs. 25%, P=0.005). No significant difference of response rate was found between patients within the target or not.ConclusionsA simplified samples PK strategy was developed for docetaxel AUC simulation. The target range of docetaxel AUC in Chinese HNC patients was suggested at 2.5–3.7 µg·hr/mL for reduced toxicity without compromising efficacy of docetaxel treatment.

Incidence and time course of neutropenia in patients treated with rituximab‐based therapy for non‐malignant immune‐mediated hematologic diseases

Incidence and time course of neutropenia in patients treated with rituximab‐based therapy for non‐malignant immune‐mediated hematologic diseases

Abstract P5-14-12: Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector

Abstract Introduction: Use of pegfilgrastim in patients who are at high risk of febrile neutropenia (>18%) results in a 94% reduction in febrile neutropenia. Use of pegfilgrastim is also associated with increased chemotherapy Relative Dose Intensity (RDI) due to fewer dose reductions, delays and discontinuations. Higher RDI has been associated with increased survival. Pegfilgrastim use historically required patients to return the day after chemotherapy. Introduction of the on-body injector (OBI) allows for next day delivery of growth factor without patients having to come back to the clinic. We conducted a study comparing neutropenia rates, dose delays and total cost of care for breast cancer patients receiving chemotherapy with high risk of febrile neutropenia who received (1) no pegfilgrastim, (2) pegfilgrastim via pre-filled syringe (PFS), (3) pegfilgrastim via OBI. Methods: The data utilized for this study originates from the EHRs, practice management systems and CMS claims obtained as part of the Oncology Care Model (OCM) for eight practices supported by Integra Connect Population Health. Using our harmonized data model, DTX, we constructed synthetic chemotherapy episodes of care. Each episode began with an administration of a chemotherapy regimen defined as having a high risk of febrile neutropenia per NCCN. The episode ended the day of the next chemotherapy administration, or after 14 days if no subsequent chemotherapy was given. Each episode was assigned to a cohort, no pegfilgrastim, pegfilgrastim via PFS, or pegfilgrastim via OBI. To evaluate the efficacy and toxicity associated with pegfilgrastim administration, we conducted a matched cohort analysis. Patients were matched based on age, sex, cancer type, number of comorbidities, regimen, chemo start date (within 90 days), whether the administration was the last cycle of chemotherapy, and OCM provider quality metrics. Results: Compared with no pegfilgrastim, PFS episodes had 9.9% less grade IV neutropenia (ANC < 500, p < 0.001) and 5.6% fewer dose delays (p=0.0014, n=916 in each arm). Compared with OBI, PFS episodes had 0.3% less grade IV neutropenia (p=0.47) and 5.3% fewer dose delays (p=0.009, n=2,727 in each arm). Exploratory analysis highlighted differences in physician office and hospital utilization. PFS episodes include more non-chemotherapy office visits than OBI episodes (2.1 vs 1.3, p < 0.001). PFS patients are more likely to have an unplanned office visit (64% vs 23%, p < 0.001) and more likely to receive hydration during an episode (34% vs. 21%, p = 0.021). PFS episodes include less hospital utilization compared with OBI episodes. OBI episodes are 23% more likely to include hospitalization (5.0% vs 6.2%, p=0.031). Discussion: As expected, this observational real-world analysis shows that the use of pegfilgrastim via PFS or OBI is associated with reduced neutropenia rates and reduced dose delays compared with no pegfilgrastim. Comparing PFS with OBI, we see similar neutropenia rates, but PFS shows fewer dose delays and fewer hospitalizations. Exploratory analysis provides some insight into these dose delays and related health care utilization. Our analysis shows that patients returning next day to the cancer center to receive pegfilgrastim frequently receive other services such as labs and hydration. These services lead to fewer dose delays, perhaps because toxicities other than neutropenia are detected earlier in the episode and can be managed in the office. This implies that use of PFS may be used as part of a strategy to shift site of service for management of side effects into the physician office and away from hospitals and emergency departments. Citation Format: Jennifer Webster, Jeffrey Scott, Danielle Wieland, Joseph Donaldson, Ash Malik, Rushir Choksi. Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-12.

Abstract GS6-01: Oral paclitaxel with encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: A phase III clinical study in metastatic breast cancer

Abstract Intravenous paclitaxel (IV Pac) is an efficacious chemotherapeutic agent against multiple cancers including metastatic breast cancer (mBC). We hypothesized that the high peak concentration with IV Pac may be responsible for peripheral neuropathy. We have developed an orally administered Pac made bioavailable through the combination with the minimally absorbed P-glycoprotein pump inhibitor encequidar (Pac+E). The pharmacokinetic exposure (AUC) matches that of IV Pac 80 mg/m2 with peak concentrations that are approximately 1/10 of IV Pac.Objective: To determine the efficacy and safety profile of oral Pac+E vs IV Pac in patients with mBC.Patients/Methods: This is a pivotal, Phase 3, open-label, randomized study of oral 205mg/m2 Pac+E for 3 days/week vs IV Pac at the labeled dose of 175mg/m2 q3weeks (NCT02594371). Subjects were randomized 2:1 to Pac+E vs IV Pac. The primary endpoint is radiologically confirmed tumor response rate (CR and PR) at two consecutive timepoints, 3-6 weeks apart, by study Day 160 using RECIST v1.1 criteria, as assessed by the blinded, independent central radiology company (Intrinsic Imaging). Progression-free survival (PFS) and overall survival (OS) were secondary endpoints.Results: A total of 402 mBC patients were enrolled (Pac+E 265 vs IV Pac 137); demographics were balanced. A similar percentage of subjects in each treatment group received prior taxane therapy (Pac+E, 28%; IV Pac, 31%). For the ITT population, final analysis of the primary endpoint of confirmed tumor response demonstrated a statistically significant difference between treatments; Pac+E 35.8% vs IV Pac 23.4%, a difference of 12.4%, p=0.011, favoring Pac+E. For the protocol defined mITT population (baseline evaluable scans and received at least 75% of the first cycle of dosing) the confirmed response rates were 40.4% for Pac+E vs 25.6% for IV Pac (p=0.005). For the population with evaluable post-baseline scan, the confirmed response rates were 50.3% for Pac+E vs 29.6% for IV Pac (p=0.0005). Tumor response in all clinically important subgroups was consistent with the overall confirmed response profiles. Responses were durable. Ongoing analysis of duration of confirmed response showed the median durations were39.0 weeks for Pac+E vs 30.1 weeks for IV Pac. Ongoing analysis of OS in the prespecified mITT population favors Pac+E (p=0.035) with a median of 27.9 months vs 16.9 months for Pac+E and IV Pac, respectively. Ongoing analysis of PFS in the prespecified mITT population shows a strong trend favoring Pac+E (p=0.077) with a median of 9.3 months vs 8.3 months. The Pac+E group had a lower incidence of alopecia and a lower incidence and severity of neuropathic AEs compared to IV Pac (17% versus 57% respectively to Week 23), with Grade 3 neuropathic symptoms observed in 1% for Pac+E vs 8% for IV Pac. The toxicity profile of Pac+E was generally similar to IV Pac. However higher rates of neutropenia, infection and gastrointestinal AEs were observed in Pac+E group. The risk of serious AEs on both treatments was highest among subjects with pre-treatment evidence of hepatic impairment and the protocol was amended to address this issue. Conclusion: Oral paclitaxel + encequidar is the first orally administered paclitaxel shown to be superior to IV paclitaxel for confirmed response, progression-free survival, and overall survival, with minimal clinically meaningful neuropathy. Citation Format: Gerardo Umanzor, David L Cutler, Francisco J Barrios, Rosa H Vassallo, Marco A Chivalan, Suyapa A Bejarano, Julio R Ramirez, Luis Fein, E Douglas Kramer, Rubio D Kowalyszyn, Hui Wang, John Goldfinch, Taryn Moore, Rudolf MF Kwan. Oral paclitaxel with encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: A phase III clinical study in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS6-01.

Neutropenia Is an Underrecognized Finding in Pediatric Primary Immunodeficiency Diseases: An Analysis of the United States Immunodeficiency Network Registry.

The frequency of neutropenia in pediatric primary immunodeficiency disorders (PIDDs) is unknown and potentially underappreciated. Our study aimed to determine the overall frequency and severity of neutropenia in children diagnosed with a PIDD entered in the United States Immunodeficiency Network (USIDNET) patient registry. Neutropenia data and demographic/clinical information from 1145 patients younger than 21 years of age was obtained from the USIDNET registry. Neutropenia is more common in PIDD patients entered within the USIDNET registry than previously appreciated. There was a >10% occurrence rate of neutropenia in all broad primary immunodeficiency categories as well as in nearly all individual PIDDs. Neutropenia frequency was greater in African American pediatric PIDD patients than in white or Asian patients. The degree of neutropenia did not associate with mortality in pediatric patients with a PIDD. Although our study did not assess the frequency of PIDD in patients presenting with neutropenia, the possibility of a primary immune disorder should be considered in patients with idiopathic neutropenia.

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as second-line treatment for advanced pancreatic adenocarcinoma: A real-world analysis.

711 Background: Therapy options for second-line treatment of advanced pancreatic adenocarcinoma (PDAC) are limited and preferred regimens have not been established. This study compared the efficacy and safety of modified FOLFIRINOX (mFFX) and sequential chemotherapy (FOLFIRI/FOLFOX) as second-line treatment for advanced PDAC. Methods: This was a retrospective single-center analysis of all patients who received mFFX or sequential chemotherapy between December 2014 and May 2019 as second-line treatment for advanced PDAC. The sequential arm included all patients intended to be treated with sequential chemotherapy even if finished with either FOLFIRI or FOLFOX. For efficacy analysis, progression-free survival (PFS), overall survival (OS), and response rate (RR)of all the patients, excluding those with locally advanced pancreatic cancer (LAPC), were evaluated. For safety analysis, we evaluated the incidence of grade ≥3 adverse events in all the patients. Results: Seventy-four patients (mFFX 44; sequential 30) were included.The patients characteristics (mFFX/sequential) are as follows:median age 64/67 years, performance status (ECOG) 0 50%/53%, and LAPC 16%/13%. In contrast to sequential therapy, the mFFX group showed better OS and RR. However, there was no significant difference between mFFX and sequential therapy in PFS (median 4.4 [95% confidence interval (CI) 1.8-7.9] vs. 4.6 [95% CI 2.0-6.2] months; hazard ratio [HR] 0.88 [95% CI 0.51-1.56]; p = 0.657), OS (median 10.6 [95% CI 5.9-13.8] vs. 8.5 [95% CI 5.0-12.2] months; HR 0.71 [95% CI 0.37-1.41]; p = 0.318), and RR (8.1% vs. 3.8%; odds ratio 1.94 [95% CI 0.19-19.87]; p = 1.000). In the safety analysis, grade ≥3 rates of neutropenia, febrile neutropenia, and anorexia were 36.4%, 6.8%, and 16.0%, respectively, with mFFX and 0%, 0% and 3.3%, respectively, with sequential chemotherapy. Conclusions: Whereas certain trends were observed, there were no significant differences in efficacy between mFFX and sequential chemotherapy. Considering the incidence of grade ≥3 adverse events with mFFX, sequential chemotherapy could be considered as one of the second-line treatment options for advanced PDAC.

First-line drug selection versus sequential treatment in advanced pancreatic cancer: Does it really matter? Multi-institutional Canadian perspective.

673 Background: Folfirinox (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine (G) in the first line treatment (1LTx) for advanced pancreatic cancer (APC). Yet, the optimal 1LTx selection nor sequential Tx (ST) has not been fully established. Therefore, the best choice for 1LTx is a matter of debate often influenced by access to drugs. This analysis was conducted to compare outcomes based on 1Ltx selection and ST in APC. Methods: We assessed patients (pts) with APC who received either FFX or GN as 1LTx during 2010-2019 at three Canadian institutions. As well as the ST used. The main objective was to assess survival. Kaplan method and log-rank test were used for survival curves. Results: This retrospective study included 231 pts; 1LTx included 143 pts on FFX and 88 pts on GN. FFX pts were predominantly male; 89(62.2%) vs 46(52.3%) and slightly younger (median age 62 vs 66) than GN. WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. There were more grade 3-4 toxicity in FFX vs GN group: GI 55 (38.5%) vs 15 (17%) and hematologic 51 (35.4%) vs 20 (22.7%) respectively. Grade 3-4 neutropenia rates were similar in both regimens. The median PFS of FFX was 5.5 months (95% CI: 5.0-6.7) vs 5.1 (95% CI: 3.8-7.1) with GN (p=0.37). The median OS with FFX was 9.3 months (95% CI: 7.5-11.1) vs 10.2 (95% CI: 6.8-11.3) with GN (p=0.81). There were not statically significant. Table shows Tx frequency across 4LTx. 2LTx and beyond regimens included G, GN, FFX, Capecitabine, Irinotecan liposome plus 5-FU, Irinotecan and clinical trials. Conclusions: Our results revealed that pts who received 1LTx FFX or GN had similar PFS and OS even though 1LTx FFX group was younger with better PS, allowing to continue 2-4LTx more frequently when compare with 1LTx GN group. Therefore, 1LTx selection appear to have more impact in our pts rather than ST, whereas GN is less toxic and seems a preferable 1LTx choice for most pts. FFX could be reserved for young high-performance pts. [Table: see text]

Risk factors for severe neutropenia among pancreatic cancer patients receiving nab-paclitaxel and gemcitabine combination therapy.

684 Background: Albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine combination therapy (GnP therapy) significantly extends overall survival in patients with metastatic pancreatic cancer, compared to conventional gemcitabine monotherapy. However, severe neutropenia (Grade ≥ 3) occurred in 67.6% of patients in the Japanese phase I/II trials of GnP therapy, and is often a limiting factor. The purpose of this study was to identify the risk factors for severe neutropenia in pancreatic patients receiving GnP therapy in clinical settings. Methods: A retrospective study of 222 consecutive patients with pancreatic cancer who received GnP therapy at the Cancer Institute Hospital from December 2014 to December 2016 was conducted. Univariate and multivariate analyses were used to compare blood test values and patients’ characteristics between patients with no neutropenia or Grade 1/2 (non-serious) neutropenia and those with Grade ≥ 3 (severe) neutropenia. Results: There were 19 patients (8.6%) with modified FOLFIRINOX in the previous treatment history. The median doses of nab-paclitaxel and gemcitabine were 192.5 mg (range 134-277.5) and 1,545 mg (range 1,000-2,220), respectively. Severe neutropenia and febrile neutropenia occurred in 118 patients (53.2%) and 15 patients (6.8%), respectively. Multivariate logistic regression analysis indicated that ANC (absolute neutrophil count) < 3.03 x 103 /μL (OR: 4.806, 95% CI: 2.416-9.558, p = 0.000), T-Bil ≥ 0.6 mg/dl (OR: 1.964, 95% CI: 1.040-3.708, p = 0.037) and CRP < 0.13 mg/dl (OR: 2.607, 95% CI: 1.331-5.106, p = 0.005) were significant risk factors for severe neutropenia. The incidence rate of severe neutropenia was 85.7% (18/21) in patients with all three identified factors, while it was 27.7% (13/47) in patients with none of them. Age was not a risk factor in either univariate or multivariate analysis. Conclusions: Low ANC, high T-Bil, and low CRP were found to be risk factors for severe neutropenia in patients receiving GnP therapy. It would be desirable to monitor patients with these risk factors carefully, even if their values are within the standard ranges.

Real-world rates of hematology lab abnormalities and associated cost among metastatic pancreatic cancer (mPC) therapeutic regimens.

670 Background: Low hematologic counts are a common, costly side effect of chemotherapy. This observational study examines rates and associated cost to treat. Methods: Data on adverse events (AEs) were extracted from the clinical Flatiron Health database for mPC patients (pts) from 01/2014-01/2019. Anemia, neutropenia, and lymphopenia occurrence was assessed via diagnosis codes and structured lab data. Costs due to AEs were derived from a claims analysis of mPC pts from 2013-2017 in Medicare Limited Data Set claims. Mean adjusted incremental costs (ICs) were estimated by comparing 30-day costs of pts with and without AEs, with controls selected among pts without AEs with the same regimen and line of therapy, when at least 80 cases/controls were identified. Results: 4592 treated mPC pts were identified (median age at diagnosis: 68y, IQR: 61 – 75). 1138 pts were treated with FOLFIRINOX (FFX) in first-line (1L), 2295 pts with 1L gemcitabine plus nab-paclitaxel (gem-nab), 218 pts with second-line (2L) FOLFOX, 56 pts with 2L FOLFIRI, and 178 pts with 2L liposomal irinotecan (nal-IRI) based therapy. Observed rates of anemia and neutropenia are shown in the table below. Lymphopenia rates were similar across regimens and ICs were not statistically significant. ICs for patients with any grade anemia were $3864, $3818, $3536, $3978, and $2963 for FFX, gem-nab, FOLFOX, FOLFIRI, and nal-IRI treated pts, respectively. ICs for pts with any grade neutropenia were $2382 for FFX, $2440 for gem-nab, $2688 for FOLFOX, $3551 for FOLFIRI and $2307 for nal-IRI. Conclusions: Any grade anemia ICs ranged from $2963 [$1544, $4400] (nal-IRI) to $3978 [$2241, $5817] (FOLFIRI), and any grade neutropenia ICs ranged from $2307 [$703, $4313] (nal-IRI) to $3551 [$1227, $6039] (FOLFIRI). Pts treated with nal-IRI had similar any grade AE rates but lower ICs, which suggest lower severity of AEs. These results are consistent with Flatiron Health’s lower rates of grades 3+ neutropenia and anemia. [Table: see text]

Infectious Complications of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Chimeric Antigen Receptor T-Cell (CART) therapy is a promising therapeutic option for patients with relapsed, refractory lymphomas. Both immunosuppression and infections are complications reported in the post-CART setting. The objective of this study was to identify rates of infectious complications and febrile neutropenia at our institution. This retrospective single center study included 38 patients with relapsed, refractory non-Hodgkin lymphoma (NHL), who received CD19 directed CAR T-cell therapy axicabtagene ciloleucel, as standard of care for the treatment relapsed NHL between January, 2018 and October, 2019. Infectious complications were identified and classified as bacterial, viral, and either as non-invasive fungal or invasive fungal. We found that 79% (30/38) of patients experienced an episode of febrile neutropenia and 22 of the 46 identified infections occurred during an episode of neutropenia. Overall, 79% (30/38) of patients had an identified infection of viral, bacterial, or fungal. Sixteen patients (42%) were found to have bacterial infections, eight patients (21%) viral infections, and 17 (45%) fungal infections. Of the forty-six infections identified, 16 were bacterial, 11 viral, and 19 fungal. The most common sites of bacterial infections noted were blood stream infections (37.5%) and pulmonary (25%) sources. The most common viral infections identified were CMV (36%), BK virus (18%), and RSV (18%). The majority of the fungal infections identified were oral candidiasis (89.5%) with only 2 patients developing an invasive mold infection. Overall, we had notable infectious findings including a high incidence of non-invasive candidiasis and occurrences of opportunistic viral infections associated with CAR-T cell therapy and lymphodepletion as compared to the literature. There is a relative paucity of guidelines and literature on supportive cares as it relates to infectious complications. We ultimately conclude that infectious complications are common adverse effects of CAR-T therapy that require more robust investigation and further evidence-based and consensus driven guidelines.

The Effect of Folinic Acid (FA) Rescue Following MTX Gvhd Prophylaxis on Regimen Related Toxicity and Transplantation Outcome: A Double Blind Randomized Controlled Study

<h3>Background</h3> The use of MTX for GVHD prophylaxis is associated with increased rates of oral mucositis (OM), delayed engraftment, hepatotoxicity and nephrotoxicity. Based on limited data, the EBMT and ELN working group recommend the use of FA-rescue to reduce MTX toxicity after alloHCT. We aimed to determine whether FA-rescue reduces the rate of MTX-induced toxicity in patients who receive post-transplant MTX for GVHD prophylaxis. <h3>Methods</h3> This is a double blind RCT conducted in 3 centers. We enrolled patients undergoing alloHCT from MSD or MUDs with a MAC regimen and PBSC grafts, and GVHD prophylaxis consisting CSA/MTX, plus ATG for MUDs. Patients were randomized to oral FA or placebo, stratified by center and conditioning intensity (standard <i>vs.</i> reduced toxicity MAC). FA administration started 24h after each MTX dose: 15 mg TID after MTX administration on day +1 and QID after MTX administration on days +3 and +6. The primary endpoint was the rate of grade 3-4 OM according to the WHO scale. A sample size of 58 subjects in each group was estimated to detect a difference in grade 3-4 OM of 50% <i>vs.</i> 25%. <h3>Results</h3> From 2/2016 through 7/2019, 52 patients with acute leukemia in CR (n = 45), MDS (n=6) or NHL in CR (n=1) were randomized to FA (n=28) or placebo (n=24). Patient characteristics were similar between groups (table). After enrolment of 52 patients, interim analysis revealed that the rate (46.6% <i>vs.</i> 45.8%, P=0.97) and duration (4 <i>vs.</i> 4 days) of grade 3-4 OM and the rate of OM of any severity (83.3% <i>vs.</i> 77.8%, P=0.65) were similar in both groups. Also, time to neutrophil and platelet engraftment, rates of febrile neutropenia and blood stream infections, VOD, need for opiates or TPN and time from HCT to discharge were not significantly different between groups. With a median follow-up of 9 months we did not observe any difference in rates of acute or chronic GVHD, DFS and OS. <h3>Conclusions</h3> The interim results, showing similar rates of grade 3-4 OM and secondary outcomes, do not support continuation of the study. FA-rescue following MTX GVHD prophylaxis does not seem to decrease regimen related toxicity and affect transplant outcomes.

Comparison of Cyclophosphamide- Versus Etoposide-Based Chemomobilization for Autologous Stem Cell Transplant in Lymphoma

Background Chemomobilization is a strategy commonly used for hematopoietic progenitor cell collection prior to high dose chemotherapy followed by autologous stem cell transplant (aHCT). Collection protocols and target yields for aHCT are variable and institution specific. At UNC Hospital, etoposide (VP16) was the preferred chemomobilization agent, but was switched to cyclophosphamide (Cy) due to a drug shortage beginning in February 2018. This study compares the efficacy and safety of Cy- and VP16-based chemomobilization strategies. Methods This is a single-center retrospective review comparing all lymphoma patients between January 1, 2017 and April 30, 2019 receiving chemomobilization with either a single dose of Cy 2 g/m2 or VP16 300 mg/m2 daily for two days. All patients received G-CSF at 10 mcg/kg rounded to nearest vial size starting approximately 24 hours after chemotherapy through completion of collection, while select patients used plerixifor per institutional algorithm. The primary endpoint was the rate of successful stem cell collection, defined as 2 × 106 CD34+ cells/kg in two or fewer apheresis sessions. Secondary endpoints included the rate of optimal stem cell collection of at least 4 × 106 CD34+ cells/kg in two or fewer apheresis sessions, time between chemomobilization and final apheresis session, rate of plerixafor use, incidence of febrile neutropenia, hemorrhagic cystitis, emergency department (ED) visits, and hospital admission rates between chemomobilization and final apheresis session as well as time to neutrophil and platelet engraftment. Results There were no differences in sex, race, or diagnoses between patients receiving Cy (n=28) vs. those who received VP16 (n=31). There was a trend towards older age in the Cy group, [median age 60 (range, 20-76) vs 53 (23-75) years; p=0.06]. All patients in both arms collected 2 × 106 CD34+ cells/kg in two or fewer apheresis sessions and there was no difference in stem cell collection of at least 4 × 106 CD34+ cells/kg in two or fewer apheresis sessions between the groups (Cy: 85.7%, VP16: 74.2%; p=0.27). Plerixafor was used in 23 patients (Cy: 39.3%, VP16: 38.7%; p=0.96). Rates of febrile neutropenia (Cy: 10.7%, VP16: 3.2%; p=0.34), hemorrhagic cystitis (Cy: 0%, VP16: 0%; p>0.99), ED visits (Cy: 10.7%, VP16: 12.9%; p>0.99), and hospital admission (Cy: 7.1%, VP16: 6.5%; p>0.99) were similar. The median days between chemomobilization and final apheresis were similar [Cy: 12 days (8-18), VP16: 12 days (8-15); p=0.32]. There were no differences in the median days to neutrophil [Cy: 11 (9-26), VP16: 11 (9-14); p=0.80) or platelet engraftment [Cy: 14 (10-38), VP16: 15 (11-149); p=0.16) between Cy and VP16 regimens. Conclusion There was no difference in the rates of successful stem cell collection or adverse events between Cy and VP16 chemomobilization. Both regimens are reasonable options for chemomobilization in lymphoma patients.

Role of G-CSF after High-Dose Post-Transplantation Cyclophospamide

<h3>Background</h3> High-dose post-transplantation cyclophosphamide (PTC) has proven to be a valuable treatment modality for the prevention of graft-versus-host disease (GVHD) after stem cell transplant (SCT). Granulocyte colony stimulating factor (G-CSF) is routinely given after PTC to improve time to engraftment. Historically, G-CSF is given on Day +5 post-SCT. However, this strategy has not been vigorously compared to other dosing strategies. We sought to assess the effect of delayed (Day +10) or omitted administration of G-CSF on various post-SCT outcomes. <h3>Methods</h3> Allogeneic SCT patients receiving PTC at standard dosing of 50 mg/kg daily on Days +3 and +4 were included in this retrospective analysis. G-CSF was given at the labeled dose of 5 mcg/kg (rounded to nearest vial) on Day +10 for 15 consecutive patients then omitted entirely for 31 consecutive patients. These results were compared to historical controls that received G-CSF beginning Day +5 after PTC. All patients received antimicrobial prophylaxis with levofloxacin, acyclovir and posaconazole. The primary outcome was to determine time to engraftment, defined as an absolute neutrophil count ≥500, in each group. A complete list of secondary outcomes is below and includes febrile neutropenia and infection rates, incidence of acute GVHD, as well as survival and relapse rates. <h3>Results</h3> Sixty-eight patients were included in the final analysis. Patient characteristics and outcomes are described in Table 1. There were no significant differences between the three groups with the exception of cells infused (p=0.04). Patients not receiving G-CSF post-transplant were associated with a statistically significant longer time to engraftment than those receiving G-CSF (22 vs. 18 days; p=0.04). There were no significant differences in all other outcomes. First year relapse and mortality were unable to be determined at this time for patients not receiving G-CSF due to this population not reaching these endpoints at time of submission. <h3>Conclusion</h3> Administration of G-CSF after post-transplant cyclophosphamide is associated with earlier neutrophil engraftment (22 vs. 18 days; p=0.04). There was no difference in time to neutrophil engraftment in patients receiving G-CSF on Day +5 vs. 10. Secondary endpoints including platelet engraftment, aGVHD, incidence of febrile neutropenia, or infections were similar among all groups. A larger, randomized study is needed to confirm these results.

Pegfilgrastim Maintains Relative Dose Intensity and Decreases Hospitalisations in Patients With Endometrial Cancer.

Data are limited regarding the use of pegfilgrastim in gynaecologic oncology. We evaluated its efficacy for maintaining dose intensity during chemotherapy. We retrospectively examined the data of 65 women (26 pegfilgrastim users) who underwent primary surgical treatment for stages IB-IV endometrial cancer and had adjuvant chemotherapy containing platinum and taxane; the primary outcome was a relative dose intensity ≥85%. In the pegfilgrastim vs. the control group, body mass index (26.6±5.9 vs. 23.4±4.4), rate of relative dose intensity ≥85% (88.5% vs. 15.4%), plus other adverse event incidences were significantly higher; rate of neutropenia, total hospital visits during chemotherapy (11.0±2.1 vs. 18±5.6 days), unscheduled hospital visits (1.1±1.8 vs. 5.8±5.1 days), and unscheduled granulocyte colony-stimulating factor injections (0.58±1.7 vs. 6.4±5.1 days) were significantly lower. Pegfilgrastim can maintain a dose intensity of ≥85% during chemotherapy for the treatment of gynaecologic cancers and decrease hospital-visit frequency.

Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre-Lishi-Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch-Schonlein Purpura Nephritis with Nephrotic Proteinuria.

Objective At present, the most appropriate management of Henoch–Schonlein purpura nephritis (HSPN) with nephrotic-range proteinuria still remains controversial; thus, the purpose of this study is to evaluate safety and efficacy of traditional Chinese medicine (TCM), Qingre-Lishi-Yishen Formula (QLYF), integrated with regular oral glucocorticoid and cyclophosphamide intravenous pulse therapeutic regimen in children suffered from moderately severe HSPN with nephrotic proteinuria. Methods From 1 January 2012, to 1 January 2016, totally 150 hospitalized children suffered from HSPN with nephrotic proteinuria were included. All were treated with glucocorticoid and cyclophosphamide, and 100 of them were treated with integrative traditional Chinese decoction QLYF. Patients were followed up for 2 years. Rate of adverse event occurrence, short-term clinical effects, long-term clinical effects, and TCM therapeutic evaluation were all compared. Results Total adverse event rate was lower in the QLYF group (χ2 = 5.357, p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (Conclusion Compared with merely using regular oral glucocorticoid plus cyclophosphamide pulse therapeutic regimen, the therapeutic regimen that integrates QLYF with the abovementioned western medicine might be a safe means to decrease the occurrence rate of adverse events and improve short-term and long-term clinical effects in children who suffered from moderately severe HSPN with nephrotic proteinuria.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period

Background. There exist different data on how the administration of granulocyte colony-stimulating factor (G-CSF) after autologous hematopoietic stem cell transplantation (auto-HSCT) affects the duration of post-transplantation agranulocytosis in multiple myeloma (MM) patients. Aim. To study the effect of G-CSF, administered after auto-HSCT to MM patients, on the duration of neutrophil engraft-ment, febrile neutropenia rate, and hospitalization duration. Materials &amp; Methods. The trial included 36 MM patients aged 42-69 years (median 59 years), 16 of which were not treated with G-CSF (1st group), and 20 patients received a single injection of 6 mg pegylated G-CSF on Day +4 or Day +5 (2nd group). Results. Patients of the 1st group were significantly younger than patients of the 2nd group: median 55.5 and 61 years, respectively (p = 0.006). There were no differences with respect to the number of patients who previously received lenalidomide, the overall and very good partial response rate, the number of the first and repeated auto-HSCTs, and the number of melphalan conditioning regimens. The patients who received G-CSF engrafted neutrophils on day 11 (median) after auto-HSCT, i.e. earlier than patients without G-CSF administration who engrafted neutrophils on day 13 (p = 0.006). In the 1st group intravenous antibiotics were administered for a longer time than in the group with G-CSF: median 13 and 11 days, respectively (p = 0.04). In 2 patients from the group without G-CSF sepsis was diagnosed. G-CSF administration led to a shorter hospital stay: median 16 and 18 days in the 1st and 2nd groups, respectively (p = 0.08). There were no differences in the number of patients with febrile neutropenia. Conclusion. G-CSF administration improves the course of the post-transplantation period in MM patients. The final decision on the feasibility of G-CSF administration after auto-HSCT can be made after more clinical observations are available.