Growth Factor Support Research Articles

Paclitaxel-induced peripheral neuropathy in early-stage breast cancer patients.

e12503 Background: Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and can persist for up to two years after completing treatment, greatly affecting both the course of chemotherapy and quality of patients. Few studies have characterized the side effect profiles of two commonly used paclitaxel-based adjuvant regimens, dose-dense biweekly paclitaxel with growth factor support (ddP, 175 mg/m2 biweekly for four cycles) and weekly paclitaxel (wP, 80 mg/m2 weekly for 12 cycles). Conflicting results exist regarding the incidence of paclitaxel-induced neuropathy related to either administration scheme. Methods: This is a data-only retrospective cohort study that consisted of adult patients with early-stage breast cancer who received either ddP or wP at Kaiser Permanente Diablo Service Area (Walnut Creek and Antioch Medical Centers) between January 1, 2010 and January 1, 2019. The primary endpoint was the proportion of patients with dose-limiting chemotherapy-induced peripheral neuropathy (DL CIPN). Results: 244 patients were included in the final analysis with 159 and 85 patients receiving wP and ddP, respectively. Baseline demographics were well matched between the two groups. There was no significant difference in the proportion of patients who experienced DL CIPN with wP (17.6%) compared to ddP (19.1%) (p = 0.647). Grade 3 or 4 adverse events occurred in 8.9% of patients who received wP and 10.6% of patients who received ddP. No significant difference was observed (p = 0.650). Conclusions: The results of this study support the current National Comprehensive Cancer Network (NCCN) guidelines, which recommend dose-dense doxorubicin and cyclophosphamide (ddAC) followed by either sequential wP or sequential ddP with growth factor support as preoperative and/or adjuvant therapy for the treatment of early-stage breast cancer. The selection of an appropriate paclitaxel schedule is provider preference and largely based on the consideration of patient tolerability. These findings suggest that the concern for paclitaxel-induced peripheral neuropathy, including DL CIPN, may potentially play a smaller role in helping guide clinicians who are choosing between the two paclitaxel-based adjuvant regimens.

Phase I/II study of R-ICE (rituximab-ifosfamide-carboplatin-etoposide) with lenalidomide (R2-ICE) in patients with first-relapse/primary refractory diffuse large B-cell lymphoma (DLBCL) in academic and community cancer research united (ACCRU) network.

TPS8073 Background: Response rates to salvage immunochemotherapy in patients with DLBCL relapsing after or refractory (R/R DLBCL) to front line therapy remain unsatisfactory. Lenalidomide (Len) has significant single agent activity in relapsed/refractory DLBCL. The addition of lenalidomide (Len) days 1-7 to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in phase 1b study (Feldman T, et al. BJH, 2014). We developed phase I/II study to evaluate the safety and efficacy of the addition of Len (extended to 14 day schedule) to RICE (R2-ICE) for R/R-DLBCL patients who are candidates for stem cell transplant. Methods: The phase I portion was designed to determine the maximally tolerated dose Len in combination with RICE using the standard cohort 3+3 design. The escalation dose levels were 15 mg and 20 mg daily x 14 days. Prophylactic aspirin and growth factor support is mandatory. After 2 cycles of therapy response is evaluated with a PET/CT scan; the responding patients are eligible for 1-2 additional cycles of R2ICE as a bridging before HDC/SCT. The estimated overall response rate for two cycles of R-ICE in R/R DLBCL to RCHOP was estimated to be approximate 45%. We hypothesize that the addition of lenalidomide in the relapse setting could increase the overall response rate by approximately 20%. The one-stage design with an interim analysis being utilized in phase 2 requires 45 evaluable patients (one sided alpha = 0.09, power 90%). For Phase I, all types of B-cell lymphomas were eligible. For phase II portion only DLBCL patients are eligible per central pathology review. Other eligibility criteria include: received one line of previous anti-lymphoma therapy, ≥ 2 weeks from completion of prior anti-lymphoma therapy, candidate for HDC and SCT, adequate organ (creatinine clearance ≥ 60ml/min by Cockcroft-, total bilirubin ≤ 2 × ULN) and bone marrow function (ANC) ≥1500/mm3; platelet count ≥75,000/mm3). The use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed. 9 patients cleared phase 1 without DLT and dose of 20 mg days 1 -14 was recommend for phase 2 part (RP2D) of the study. The phase 2 study passed interim futility analysis and accrual continues. Correlatives include cell of origin by Nanostring, Myc/bcl2 expression and by FISH and minimal residual disease. PET scans are centrally reviewed including metabolic tumor volume. Clinical trial information: NCT02628405 .

A phase Ib study of ribociclib in combination with doxorubicin in advanced soft tissue sarcomas (aSTS).

11548 Background: aSTS are typically treated with single agent doxorubicin (dox). CDK4 inhibitors such as ribociclib (ribo) may have a role in treating STS, which frequently rely on hyperphosphorylation of Rb to evade the Rb checkpoint. We hypothesized that dox efficacy could be increased by inhibiting Rb phosphorylation with a short course of ribo, then removing ribo to permit cell cycle progression prior to dox, thus potentiating the DNA-damaging effects of dox. Methods: Open label, dose-finding study of ribo and dox in dox-naïve patients (pts) with Rb+ aSTS. Rb status determined by IHC. Primary objective to determine the recommended phase 2 dose (RP2D). Secondary objective of anti-tumor activity. Pts received ribo 400-600 mg PO QD x7d followed by 72h rest before dox 60-75 mg/m2 IV, q21d. Pts free from progression of disease after 6 cycles continued on ribo maintenance at 600 mg QD q3/4wk. Dose-limiting toxicity (DLT) period was cycle 1, with target toxicity rate of 30% using a modified toxicity probability interval (mTPI) design. Growth factor support was not allowed during DLT period. Results: 9 screened pts were ineligible by Rb status. 16 pts enrolled with 15 evaluable for dose determination (7 dedifferentiated LPS, 8 other subtypes). 4 of 7 pts treated at starting dose level (400 mg ribo, 75 mg/m2 dox) had a DLT; all febrile neutropenia. 1 of 8 pts treated at dose level -1 (400 mg ribo, 60 mg/m2 dox) had a DLT of gr4 anemia. Febrile neutropenia events occurred during cycle 1, when growth factors were prohibited. Toxicity was similar to historical dox AEs (Table). Two partial responses for overall response rate (ORR) of 13%. Five (33%) were progression-free at 18 wks. Correlative studies ongoing. Conclusions: This study determined a RP2D of ribo 400 mg with dox 60 mg/m2 when used in combination for the treatment of aSTS. Clinical trial information: NCT03009201 . [Table: see text]

Impact of empirically eliminating 5-fluorouracil (5-FU) bolus and leucovorin (LV) in patients with metastatic colorectal cancer (mCRC) receiving first-line treatment with mFOLFOX6.

4022 Background: Systemic chemotherapy with a 5-FU-based regimen, such as mFOLFOX6, is the preferred first line treatment option for mCRC. Due to hematologic toxicities associated with the 5-FU bolus component, providers may choose to eliminate it empirically in patients receiving palliative therapy. This study aimed to assess the impact of empirically eliminating the 5-FU bolus and LV from first line treatment with mFOLFOX6 in mCRC. Methods: This was a retrospective chart review of patients ≥ 18 years old with mCRC receiving palliative first line mFOLFOX6 chemotherapy with (bolus) or without (non-bolus) the 5-FU bolus and LV components from January 1, 2015 through August 31, 2019 at Moffitt Cancer Center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) defined as partial response and stable disease at first scan, utilization of growth factor support and safety. Results: Data analysis cutoff was December 31, 2019, with 61 patients included in the bolus arm and 72 in the non-bolus arm. Median follow-up time was 21.8 months. No difference was found in median PFS (8.12 vs. 6.64 months, p=0.787) or OS (29.36 vs. 21.6 months, p=0.395) between the bolus and non-bolus arms, respectively. Observed DCR at first scan was similar between both arms (47.3% vs. 52.7%, p=0.44). Utilization of growth factor support was significantly higher in the bolus arm (73.7% vs. 26.3%, p=0.012). Fewer grade ≥ 3 treatment-related hematologic adverse events (AE) were seen in the non-bolus arm (37.7% vs. 22.2%, p=0.058) (table). Conclusions: This is the only study to date that analyzed the impact of empirically eliminating 5-FU bolus and LV from first line palliative therapy with mFOLFOX6 in mCRC. Results showed no significant difference in median PFS or OS. Despite reduced growth factor utilization, the non-bolus arm demonstrated a favorable safety profile with less treatment-related hematologic grade ≥ 3 AE. The results of this study warrant consideration of empirically eliminating 5-FU bolus and LV from the mFOLFOX6 regimen to avoid additive toxicities without negatively impacting efficacy. [Table: see text]

EMA vs EMACO in the treatment of gestational trophoblastic neoplasia

ObjectiveTo compare experiences with EMA versus EMACO in the treatment of gestational trophoblastic neoplasia. MethodsThe medical records of women diagnosed with GTN at the New England Trophoblastic Disease Center from 1986 to 2019 were reviewed, and women receiving EMA or EMACO as their first multiagent regimen were eligible. Clinical characteristics, treatment, outcomes, and adverse events were compared between the two groups. ResultsWe identified 44 and 39 patients who received EMA and EMACO, respectively. The complete remission rate was significantly higher in the EMA group (97.7%) than in the EMACO group (71.8%) (p = 0.001). However, patients receiving EMACO were more likely to have adverse prognostic factors such as higher median prognostic risk score (8 vs 4, p < 0.001), non-molar antecedent pregnancy (59 vs 27.3%, p = 0.014) and distant metastasis (64.1 vs 47.7%, p = 0.017). Time to complete remission was also similar (p = 0.947) with a median of 12 weeks with EMA and 13.1 weeks with EMACO. There was no significant difference in treatment delays or use of adjuvant surgery. After multivariate analysis, chemotherapy regimen (EMA or EMACO) did not retain prognostic significance for remission. Overall toxicities were more frequent in EMA (60.2 vs 32.7%, p < 0.001), especially neutropenia, but this did not delay treatment and likely resulted from less growth factor support (18.2 vs 48.7%, p = 0.003). ConclusionsWhen controlling for other prognostic factors, outcomes with EMA appear similar to EMACO. It may be worthwhile to investigate whether EMA, a simpler and less costly regimen, may be as effective as EMACO in the treatment of GTN.

Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.

A phase I study of guadecitabine (SGI-110) plus cisplatin in patients with platinum refractory germ cell tumors.

408 Background: Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. Platinum-refractory germ cell tumors (GCT) showed significant DNA hypermethylation compared to platinum sensitive tumors. In preclinical studies, GCT were extremely sensitive to low dose decitabine which restored sensitivity to cisplatin in cell lines. We aimed to assess the safety and clinical activity of guadecitabine in combination with cisplatin in patients with platinum-refractory GCT. Methods: In this open-label, phase 1 study, patients with GCT refractory to or had relapsed after platinum-based treatment were treated with subcutaneous (SQ) guadecitabine, once-daily for 5 consecutive days, followed by cisplatin on day 8 with growth factor support (GFS) in a 28-day treatment cycle. A modified toxicity probability interval (mTPI) dose-escalation design was used in which we treated patients with guadecitabine doses of 30-45 mg/m2 plus cisplatin 100 mg/m2 up to 6 cycles until progression or intolerable toxicity. The primary objective was to assess safety and tolerability of the combination, determine the maximum tolerated dose (MTD). Secondary objective was objective response rate (ORR). Results: Fourteen patients with incurable disease were enrolled. Primary site were testis 11, mediastinum 2, and ovarian 1. All progressed after at least 2 lines of standard of care chemotherapy including HDCT. Dose-limiting toxicities were neutropenic fever. Most common toxicities were neutropenia (82% any grade), thrombocytopenia (42%), anemia (33%), neutropenic fever (8%), and diarrhea (8%). The maximum tolerated dose of guadecitabine was 30 mg/m2 x 5 days and cisplatin 100 mg/m2. We observed 2/14 complete response lasting more than 6 months, 2 partial response and 1 stable disease. ORR 28.5%. Conclusions: We report the first study of chemo-priming with epigenetic therapy in GCT. Guadecitabine 30 mg/m2 x 5 days and cisplatin 100 mg/m2 with GFS was safe and tolerable and showed promising activity with 4/14 responses in this highly treatment refractory patient population. Clinical trial information: NCT02429466.

Abstract P2-14-12: Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy

Abstract Background: Eflapegrastim (E) represents the first myeloid growth factor innovation in more than 15 years. A novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), E consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a polyethylene glycol linker. Preclinical and Phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for E versus pegfilgrastim (P). Two independent randomized Phase III trials comparing fixed dose E and P (E 3.6 mg G-CSF and P 6.0 mg G-CSF) for the management of chemotherapy-induced neutropenia (CIN) have recently been completed. Both trials met the primary endpoint of non-inferiority for E vs P in Cycle 1 duration of severe neutropenia (P&amp;lt;.001). Here we provide an integrated summary of the safety of E administered at a fixed dose in a pre-filled syringe. Patients and Methods: Patients with early-stage breast cancer (ESBC) who were candidates for adjuvant or neoadjuvant chemotherapy were randomized 1:1 in two open-label Phase III trials to E 13.2 mg (3.6 mg G-CSF) or standard P (6 mg G-CSF) administered on Day 2 following TC (docetaxel/cyclophosphamide) chemotherapy on Day 1 of each of 4 cycles. Blood for CBC and serum chemistry was collected in every cycle. Safety assessments began with the first dose of TC and continued for one year after the last dose of study drug. AEs and laboratory values were graded according to NCI CTCAE version 4.03. Immunogenicity was assessed from blood samples collected on Day 1 of each cycle, at the end-of-treatment visit, and at 6- and 12-month follow-up visits. Results: A total of 660 patients who received at least one dose of eflapegrastim (n=334) or pegfilgrastim (n=326) were included in this integrated safety analysis. The two treatment groups were well balanced for demographics and baseline disease characteristics. The mean age was 59y, ~40% were aged &amp;gt;65y, ~54% weighed &amp;gt;75kg, and ~80% were treated in the adjuvant setting. Median relative dose intensity for T and C was &amp;gt;99% for both groups. A similar percentage of patients in both treatment groups discontinued treatment due to AEs (4% E vs 6% P), with 2% in each group discontinuing due to AEs related to E or P. Serious AEs were similar in both groups (15% each). Incidence of AEs irrespective of causality were also similar between groups (74% E vs. 72% P). No notable differences between groups were observed in the types of study-drug-related AEs. The majority of study-drug-related AEs occurred with an incidence ≤10% for both E and P. As expected with myeloid growth factors, study-drug-related AEs occurring in &amp;gt;10% in either group were bone pain (E vs P: 33% vs 34%), arthralgia (15% vs 10%), back pain (14% vs 9%), myalgia (14% vs 9%), and headache (11% vs 8%). Incidence of febrile neutropenia and neutropenic complications were similar and less than 5% in each treatment group. No leukocytosis, splenic rupture, or anaphylaxis was reported in any patient receiving E or P. The overall incidence of immunogenicity was similar in both groups and there was no demonstrable impact on clinical safety or efficacy. Conclusions: Two large, randomized Phase III trials (Total n=660) of E vs P administered once-per-cycle showed E at a lower G-CSF dose to be safe and effective for the prophylaxis of CIN in patients with ESBC receiving TC chemotherapy. E is a novel long-acting rhG-CSF with increased potency and similar toxicity to P and may provide an attractive alternative for growth factor support of patients at high risk for CIN-related complications. Citation Format: Lee S Schwartzberg, Gajanan Bhat, Julio Peguero, Richy Agajanian, Jayaram Bharadwaj, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Shanta Chawla, Francois Lebel, Patrick W Cobb. Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy [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 P2-14-12.

Phase I dose-escalation trial of trifluridine/tipiracil (TAS-102) and temozolomide in the treatment of advanced neuroendocrine tumors.

615 Background: Systemic chemotherapy plays a role in treating neuroendocrine tumors. Trifluridine/tipiracil (FTD/TPI), known as TAS-102, is an antineoplastic agent that is non-cross resistant with 5-fluorouracil and capecitabine and that has a different toxicity profile. We are presenting results from a phase 1 portion of the study evaluating safety of FTD/TPI in combination with TMZ in patients in neuroendocrine tumors. Methods: Phase 1 portion to the study utilized “3+3” design to determine maximum tolerated doses (MTD) of FTD/TPI and TMZ when administered in combination. Patients with advanced NETs of any grade were eligible for participation. FTD/TPI was taken twice a day on days 1-5 and 8-12 and TMZ was taken daily on days 8-12 of a 28 day cycle. 3 dose levels (Lv) were evaluated. FTD/TPI was started at a goal dose of 35 mg/m2 twice daily. Three doses of TMZ were studied: 100, 150 and 200 mg/m2. Growth factor support was required during DLT evaluation period for all patients starting with the fourth subject on study. Results: Sixteen evaluable subjects (6 females, median age 64) enrolled in the phase 1 portion of the study (4 on Lv1, 6 on Lv2, 6 on Lv3). 3/16 had high-grade tumors, 8/16 had non-GI or unknown primary. No DLTs were observed on Lv1. One DLT was observed on Lv2 (grade 3 fatigue and inability to resume treatment) and 1 DLT on Lv3 (grade 4 thrombocytopenia). Overall the treatment was well tolerated. 7 subjects had grade ≥3 AEs at least possibly related to treatment, with neutropenia and lymphopenia being the most common. 4 subjects required dose reductions. 7 subjects remain on active treatment. 4 subjects discontinued treatment due to AEs and 1 due to clinical disease progression. Efficacy data is being collected and will be presented at the meeting. Conclusions: This study established MTD of FTD/TPI (35mg/m2 twice daily) and TMZ (200 mg/m2). This regimen is well tolerated. Enrollment into expansion cohort for patients with advanced Grade 1-2 pancreatic NETs is ongoing (NCT02943733). Clinical trial information: NCT02943733.

A phase II, open-label pilot study evaluating the safety and activity of Nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study) (NCT03483038).

TPS790 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board, adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive FOLFNal-IRINOX regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. Clinical trial information: NCT03483038 . [Table: see text]

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged &gt; 65 years with advanced pancreatic cancer (APC).

705 Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in APC. However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients &gt; 65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged &gt; 65 years with chemo-naive APC and ECOG PS &lt; 2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. CA19-9 was measured every cycle and restaging scans were performed every two cycles. Results: Seventy-three patients (median age: 73; range: 66 - 93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months respectively. 66% of patients received growth factor support based on ASCO guidelines and no patients developed neutropenic fever. The incidence of grade &gt; 3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5% respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients respectively. Conclusions: In patients &gt; 65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with historical control from the MPACT study. This regimen allowed for less dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as favorable side effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with APC and poor performance status. Better tolerability may allow for combination with a third agent, such as a targeted or immunotherapy.

Hematologic Toxicities of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Chimeric Antigen Receptor T-Cell (CART) therapy remains a novel approach for the treatment of relapsed, refractory B-cell Lymphoma. Complications of CAR T-cell therapy including cytopenias, infections, cytokine release syndrome (CRS) and neurotoxicity require aggressive supportive care. The objective of this study was to characterize the incidence of cytopenias and the utilization of growth factor and transfusion support following CAR T-cell therapy. 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. Cytopenias included 34% grade 4 thrombocytopenia (13/38), 76% grade ≥3 anemia (29/38), and 92% grade 4 neutropenia (35/38). Thirty-four percent (13/38) of patients required platelet transfusion support, 76% of patients (29/38) required RBC transfusions, 92% (35/38) of patients became neutropenic and 81.6% (31/38) received growth factor support. Twenty-nine percent of patients were found to have recurrent neutropenia status post recovery of their initial onset. The median initial onset occurred on day +8 (0-+14) and lasted a median of 5 days (0-85 days) with a median ANC nadir of too few cells to count (0-490). The median onset for a 2nd occurrence of neutropenia occurred on day +21 (D+12- D+28) which lasted 1 day (1-11 days) with a nadir of 430 cells/mm³ (0-480). Sixteen percent of patients experienced a 3rd occurrence on day +35 (D+25-+52), lasting a median of 3.5 days (1-19 days) with a median nadir of 335 cells/mm³ (270-440). One patient had a 4th occurrence on day +28 with a nadir of 220 cells/mm³. The etiology of recurrent neutropenia described is unclear. Multiple factors may contribute including bridging therapy, infection, steroids, CRS, and growth factor support. More is data is needed to identify risk factors for recurrent neutropenia.

Hematopoietic Recovery Following Chimeric Antigen Receptor T Cell (CAR T) Therapy in Hematological Malignancies

<h3>Background</h3> Cytopenias are observed post-CAR T, yet there is minimal data delineating the pathobiology and trends thereof. We report the largest series to our knowledge thus far, of hematopoietic recovery post-CAR T and factors affecting this recovery. <h3>Methods</h3> We retrospectively reviewed 115 adult patients who received CAR T, at our center, for relapsed/refractory (R/R) B cell lymphomas after FDA approval, R/R B cell acute lymphoblastic leukemia (ALL, NCT01044069) and multiple myeloma (MM, NCT03070327). Blood counts were collected for 12 months or until censored for relapse, progression or initiation of chemotherapy/ conditioning for autologous or allogeneic stem cell transplantation (HCT)/ subsequent treatment with CAR T. Only patients with follow-up > 30 days were included. "Recovery" for the respective blood count was defined to signify absence of transfusions or risk of infections: hemoglobin > 8g/dL and platelets > 50,000/µL without transfusion support in 2 weeks and 1 week, respectively; absolute neutrophil count (ANC) > 1,000/µL and white cell count (WBC) > 3,000/µL without growth factor support in 2 weeks. "Complete countrecovery" refers to recovery per above criteria in all 4 counts. <h3>Results</h3> Eighty three patients were included (Figure 1). By 1 month (n = 83), hemoglobin, platelets, ANC and WBC recovery was noted in 61%, 51%, 33% and 28%, respectively. At 3 months (n = 41), these were 93%, 90%, 81% and 59%. Figure 2 shows recovery at subsequent months. Upon examination of potential variables in a univariate model, lack of recovery of hemoglobin, platelets, ANC and complete count recovery at 1 month was statistically significantly associated with type of CAR construct, higher grade (3-4 vs 1-2 vs none) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as well as a higher peak CRP and ferritin (data for complete count recovery in Figure 3). Additionally, lack of hemoglobin recovery at 1 month was associated with lymphodepletion using high dose cyclophosphamide (recovered vs no recovery in 58% vs 42%, <i>p</i> = 0.01) and diagnosis of ALL (65% vs 35%, <i>p</i> = <0.001). Inability to recover platelets at 1 month was associated with prior HCT (63% vs 36%, <i>p</i> = 0.04); while ANC was associated with prior HCT (87% vs 13%, <i>p</i> = 0.004) and > 3 prior lines of therapy (78% vs 22%, <i>p</i> = 0.04). At 3 months, absence of complete count recovery was associated only with the CAR T construct utilized. We also performed a sensitivity analysis using data for all 115 patients and no significant difference in univariate analysis was seen. <h3>Conclusions</h3> Our study shows that blood counts recover in most patients who have not progressed or received additional therapy by 3 months following CAR T. The association of count recovery with severity of CRS, ICANS as well as inflammatory marker levels indicates that inflammatory response post-CAR T influences hematological recovery in these patients.

Local Lung Mass Masquerading a Very Aggressive Extraskeletal Ewing Sarcoma Presenting as Bilateral Paraparesis in a Young Adult

Ewing sarcoma is typically seen in children involving long bones. Although well described, its presentation in extraskeletal tissues is relatively rare and is classified as an Ewing sarcoma family of tumors. They are mostly curable when they occur in children. An extraskeletal Ewing sarcoma in adults is uncommon, limiting the experience in adult oncologists. The biopsy is essential for definitive diagnosis, which shows small round blue cells that must be differentiated from lymphoma, embryonal rhabdomyosarcoma, and small cell carcinoma. Management is multimodal, involving surgery, radiation for local treatment of primary tumor, and systemic chemotherapy. A multidisciplinary approach, coupled with risk-adapted intensive neoadjuvant and adjuvant multi-agent chemotherapies and other modalities such as radiation and surgery for control of the primary site and metastatic disease, is needed. The primary multidrug chemotherapy regimen consists of alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and ifosfamide/etoposide (IE) given every 2 weeks with growth factor support. Prognosis and the 5-year survival rate are better for localized than the metastatic disease, and in metastatic disease, it is better for patients with lung metastasis than other metastatic disease sites. We describe a rare extraskeletal tumor arising from a lung that tested positive for Ewing sarcoma, also known as Askin’s tumor in a young adult. In our case, the tumor rapidly metastasized locally to involve the thoracic spine causing paraparesis. Timely diagnosis and early management are essential to improve outcomes. We also present how treatment can be delayed due to sepsis and emphasize the careful multispecialty approach’s importance.

Management of hematological malignancies during the COVID-19 pandemic

Patients with hematological malignancies (HM) appear to be at increased risk of acquiring COVID-19 infection and its complications. General measures to protect patients with HM from COVID-19 include limiting exposure of patients to medical environments with the use of telemedicine and virtual clinics, delaying elective diagnostic services, modifying treatment modalities in a manner that reduces the probability of further immune suppression such as shortening the treatment course or prolonging the interval between treatment courses, and growth factor support to reduce the risk of neutropenia. Reducing the threshold for packed RBC and platelet transfusions to mitigate reduced blood product supplies, and a careful attention to drug interactions in patients who get the COVID-19, are also important management measures. Physicians caring for patients with HM need to carefully evaluate each individual patient to optimize therapies, take measures to maximize safety of patients and staff, without significantly compromising outcomes. This paper discusses management of HM during the COVID-19 pandemic.

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer.

Background:Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity.Methods:Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles.Results:A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively.Conclusion:In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

Implementation of Outpatient High-Dose Cytarabine (HiDAC) for AML: Evaluation of the Impact of Transitioned Outpatient Chemotherapy in an Oncology Care Model Setting

Background: Patients with acute myeloid leukemia (AML) who achieve complete remission with induction therapy require consolidation therapy. The standard of care consolidation is HiDAC based on age and risk stratification. Consolidation therapy has historically been administered in the inpatient setting. The rising cost of inpatient care, alternative payment model implementation and patient preference has prompted institutions to consider shifting therapy to the outpatient setting. However, the safety and feasibility of outpatient high dose Cytarabine (HiDAC) consolidation therapy is not well established. The University of Arizona Cancer Center developed an Outpatient Program (OP) to facilitate administration of hematologic chemotherapy regimens in the outpatient setting. We hypothesized that OP administration of HiDAC consolidation therapy would be safe and efficacious and have large cost-savings implications under alternative payment model pilots, such as the oncology care model. Methods: We conducted a retrospective chart review on high-risk MDS/AML patients who were 18 years or older and received HiDAC consolidation therapy at UACC following induction therapy from November 1st 2013 to June 1st 2019. Interim data collection included age, risk stratification, treatment history, clinic visits, number of cycles received in the OP versus inpatient setting, supportive care, hospitalizations, and chemotherapy related adverse events. Our Outpatient HiDAC protocol consisted of a one-hour infusion for all cytarabine doses administered at 7:30am and 4:00pm, with neurologic checks prior to each dose. Growth factor support, if required was administered on the same day as the last dose of cytarabine Results: We evaluated 19 patients at our cancer center who received 52 total cycles of HiDAC consolidation therapy. The median patient age was 49.6 yrs with 21.1 % being over the age of 60. Thirty-three cycles were administered in the outpatient setting, with 19 cycles being administered inpatient. None of the patients who were administered HiDAC in either the IP or OP setting had reported clinically significant neurotoxicity (≥ grade III). Nine patients receive all of their cycles in the outpatient setting. 57.9% of our patients developed febrile neutropenia, with 47.4% of the patients requiring hospitalization for neutropenic fever. The average inpatient HiDAC length of stay was 6 days. Transitioning HiDAC to the outpatient setting led to a savings of 198 hospital days, with a corresponding cost reduction to our healthcare system of $529,650. Transitioning HiDAC to the outpatient setting also improved patient satisfaction. Conclusion: Outpatient administration of HiDAC consolidation therapy for AML patients is a safe and effective treatment option. In addition, transitioning HiDAC to the outpatient setting led to a reduced overall cost of care for AML treatment , under an OCM based practice model. Utilization of outpatient HiDAC for the outpatient setting provides a unique opportunity for select patients. Disclosures Maher: Agios: Consultancy. Anwer:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Campen:Coherus: Speakers Bureau; Teva: Speakers Bureau; Amgen: Consultancy. McBride:teva: Consultancy; Sandoz: Consultancy; Sanofi Genzyme: Consultancy.

Long-Term Outcome of Patients with Marginal Zone Non-Hodgkin Lymphoma (MZL) Treated with Yttrium-90 Ibritumomab Tiuxetan: The Mayo Clinic Experience

Background MZL is a low-grade non-Hodgkin's lymphoma (NHL) which involves lymph nodes, extranodal sites, or spleen. It is sensitive to radiation therapy, which is used in localized disease with curative intent. Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) that targets CD20. It is approved for relapsed/refractory low grade and follicular NHL. The data on its use in MZL is limited. We present long-term outcome of the largest reported cohort of MZL patients who received (90)Y-IT. Methods Medical records of patients who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2004 and December 2018 were analyzed. We selected patients with MZL and reviewed clinical data including age, gender, MZL type, clinical stage (Ann Arbor Staging System), treatment response, (90)Y-IT related adverse effects (AEs), as well as lymphoma and treatment related events. All patients received (90)Y-IT according to the standard treatment guidelines. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Twenty-one patients were identified (Table 1). The median age at diagnosis was 60 years (range, 11-81) and 71% (15/21) were female. 52% (11/21) were previously-untreated (UMZL) while 48% (10/21) were relapsed (RMZL). The median number of pretreatments in RMZL patients was 2 (range, 1-3). ECOG performance status at the time of treatment was 0 in 90% (19/21) and 1 in 10% (2/21). 62% (13/21) were stage III/IV disease at the time of (90)Y-IT therapy. The median follow-up was 8.5 years (95% CI; 4.5, 12.4); 17 (81%) patients remain alive. The ORR was 91% (19/21) with the two non-responders being in the RMZL group. The CR rate was 81% (17/21) and 65% (11/17) remain in CR at a median follow-up of 5.7 years (95% CI; 1.4, 11). Nine (43%) patients had a relapse during the study period. More relapses occurred in the RMZL group (7/10; 70%) compared to (2/11; 18%) in the UMZL group. Median PFS (whole cohort) was 10 years (95% CI; 2.1, NR) and TTNT (whole cohort) was not reached (NR) (95% CI; 2.1 years, NR). Median PFS was significantly higher in UMZL group compared to RMZL group NR (95% CI; 2.5 years, NR) vs 2.1 years (95% CI; 0.17, 9.9), respectively (Figure 1-A).Median OS (whole cohort) was 19.3 years (95% CI; 8.9, 19.3) without statistical difference in between UMZL group and RMZL group NR (95% CI; NR, NR) vs 16.6 years (95% CI; 9, 19.4), respectively (Figure 1-B). None of the 11 UMZL patients died at median follow up of 4.7 years (95% CI; 1.6, 9.2). All 4 deaths were in the RMZL group with 3 dying of transformation to high-grade lymphoma at 8, 22, and 25 months post-(90)Y-IT treatment. One patient died of myelodysplastic syndrome 7.3 years post-(90)Y-IT treatment while in CR. Toxicities were primarily hematologic. Grade ³3 neutropenia was observed in 6/21 (29%) patients with median time to nadir of 48.5 days (range, 19-70) and median time to recovery to normal absolute neutrophil count of 39.5 days (range, 7-476). Grade ³3 thrombocytopenia was observed in 3 (14%) patients with median time to nadir of 35 days (range, 19-357) and median time to recovery of 21 days (range, 2-538). Grade ³3 anemia was observed in only one patient. Only two patients required transfusions and growth factor support. Non-hematologic AEs included mild to severe fatigue in 4 patients. Conclusion RIC with (90)Y-IT is efficacious and well-tolerated in patients with previously untreated as well as relapsed MZL. As expected it appears to be more efficacious in previously untreated patients. Long-term complete remission (&amp;gt;5 years) was observed in 52% of the study population (43% of UMZL and 9% of RMZL). Combination of efficacy, tolerability, and treatment schedule most convenient for patients makes (90)Y-IT a reasonable alternative to systemic therapy with immunotherapy, chemotherapy, or chemo-immunotherapy in management of MZL. Figure 1: (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UMZL) and patients with relapsed MZL (RMZL), (B) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UMZL patients and RMZL patients. Disclosures Tun: Curis: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; DTRM Biopharma: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: The use of Yttrium-90 ibritumomab tiuxetan as a first line treatment for marginal zone lymphoma

Venetoclax and Azacitidine for Older Newly Diagnosed Patients with Acute Myeloid Leukemia: A Single-Institution Pilot Study Using Measurable Residual Disease to Guide Therapy

Venetoclax and Azacitidine for Older Newly Diagnosed Patients with Acute Myeloid Leukemia: A Single-Institution Pilot Study Using Measurable Residual Disease to Guide Therapy

Hematological Count Recovery in Patients Undergoing Treatment with Chimeric Antigen Receptor T Cells (CAR T)

Hematological Count Recovery in Patients Undergoing Treatment with Chimeric Antigen Receptor T Cells (CAR T)