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PURPOSE Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months ( P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm ( P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.Using a nested case–control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6 to 8 biomarkers, were evaluated according to a predetermined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (step 1); simultaneous split-sample discovery and validation of models (step 2); and exploratory discovery of new models (step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In step 1, one model showed comparable performance to CA125, with sensitivity, specificity, and AUC at 69.2%, 96.6%, and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In step 2, we observed a similar pattern. In step 3, a model derived from all 28 markers failed to show improvement over CA125.Thus, biomarker panels discovered in diagnostic samples may not validate in prediagnostic samples; utilizing prediagnostic samples for discovery may be helpful in developing validated early detection panels. Cancer Prev Res; 4(3); 375–83. ©2011 AACR.

Perspectives on This Article from A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer

Supplementary Materials from A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer

Treatment Emergent Adverse Events Attributed to Pembrolizumab, Any Grade.

All Treatment Emergent Adverse Events Regardless of Causality, Any Grade

Purpose:Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS.Patients and Methods:This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines.Results:Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9–56.1%], with documented disease control in 80.0% (95% CI, 61.4–92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS.Conclusions:Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

Study inclusion and exclusion criteria.

Treatment Emergent Adverse Events Attributed to Either Doxorubicin, Pembrolizumab, or Both, Any Grade

Purpose: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. Patients and Methods: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. Results: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9–56.1%], with documented disease control in 80.0% (95% CI, 61.4–92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. Conclusions: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

Background In cancer, malnutrition is common and negatively impacts tolerance and outcomes of anti-tumor therapies. The aim of this study was to evaluate the prevalence of malnutrition risk and compare the clinicodemographic features between those with high malnutrition screening tool (MST) scores (i.e., ≥ 2 of 5 = high risk for malnutrition, H-MST) to low scores (L-MST). Methods A cohort of 3585 patients (May 2017 through December 2018), who completed the MST at least once at the time of diagnosis of any stage solid tumor, were analyzed. Logistic regression tested for associations between clinicodemographic factors, symptom scores, and H-MST prevalence. Results The median age was 64 years (25–75 IQR, 55–72), with 62% females and 81% White. Most common tumor primary sites were breast (28%), gastrointestinal (GI) (21%), and thoracic (13%). Most had non-metastatic disease (80%). H-MST was found in 28%—most commonly in upper (58%) and lower GI (42%), and thoracic (42%) tumors. L-MST was most common in breast (90%). Multivariable regression confirmed that Black race (OR 1.9, 95% CI 1.5–2.4, p =

Background Aggressive large B-cell lymphomas (LBCLs) are curable, but previous studies have shown inferior outcomes in minorities. Nurse navigation programs can improve patient outcomes by providing patient support. This study presents the outcomes of White and minority patients with aggressive LBCL at an institution with an active nurse navigation program. Methods The authors prospectively collected baseline characteristics, treatment regimens, and outcome data for patients with aggressive LBCL. Navigation encounters were characterized as low or high intensity. Overall survival (OS) and progression-free survival (PFS) were calculated with Kaplan-Meier methods. Baseline characteristics were compared with Fisher exact tests. Results Two hundred four consecutive patients (47 minority patients and 157 White patients) were included. Results were presented as minorities versus Whites. There were no differences in prognostic scores (Revised International Prognostic Index score of 3-5, 43% vs 47%; P = .50), frontline chemotherapy (98% vs 96%; P = .68), or the incidence of relapsed/refractory disease (40% vs 38%; P = .74). For relapsed/refractory LBCL, similar proportions of patients underwent hematopoietic stem cell transplantation (32% vs 29%; P > .99) or chimeric antigen receptor T-cell therapy (16% vs 19%; P > .99). Enrollment in clinical trials was comparable (17% vs 14%; P = .64). More than 85% received nurse navigation, but minorities had higher intensity navigation encounters (42% vs 21%; P = .01). The 2-year OS rates were 81% and 76% for minorities and Whites, respectively (P = .27); the 2-year PFS rates were 62% and 65%, respectively (P = .78). Conclusions This study shows similar survival between Whites and minorities with aggressive LBCL, which was likely due to equal access to guideline-concordant therapy. Minorities received higher intensity navigation encounters, which may have helped them to overcome socioeconomic disadvantages.

Purpose AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. Methods In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. Results 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. Conclusions This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.

BACKGROUND: Limited stage small cell bladder cancer is curable with multi-modality therapy using external beam radiotherapy or radical cystectomy. The optimal management strategy for this rare disease is still debated, yet few case series have described patients treated after 2010. OBJECTIVE: To analyze outcomes from a contemporary cohort of patients undergoing definitive treatment. METHODS: Patients diagnosed with small cell bladder cancer after January 1, 2010 were identified from an institutional database. Clinical histories were collected by chart review. Survival outcomes were analyzed in patients who received curative-intent therapy consisting of bladder radiotherapy or cystectomy. RESULTS: Thirty patients with limited stage disease that received definitive therapy were identified. Seventeen patients received primary radiotherapy, and thirteen underwent cystectomy. Median age was 70 years. Median follow up was 39.6 months (range 7.2–95.8). The median overall survival of patients undergoing radiotherapy or cystectomy were 36.8 and 30.6 months, respectively (hazard ratio 0.99, 95% confidence interval 0.35–2.85). The median metastasis free survival for patients receiving radiotherapy was not reached, and 18.9 months in the cystectomy group (hazard ratio 0.94, 95% confidence interval 0.34–2.61). The most common sites of relapse were lymph node (n = 6) and bone (n = 5). Brain metastases were less common (n = 3). CONCLUSIONS: Patients receiving cystectomy or radiotherapy had similar outcomes in this contemporary series, but definitive comparisons are limited by the cohort size and high censoring rate (53%). Survival in our cohort is improved compared with older reports, though outcomes remain poor, reiterating the need for better therapeutic options.

Pulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.SEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.A total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P .001; DSS: 54 vs. 8 months, P .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P .001) and DSS (32 months; P .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).Treatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.

Inpatient management of sickle cell disease (SCD) vaso-occlusive crisis (VOC) often involves use of high-dose opioids, which may result in opioid-induced pruritus (OIP). This OIP is typically treated with antihistamines like diphenhydramine either orally or intravenously. The oversedation adverse effects of diphenhydramine may be magnified when given in combination with high-dose opioid therapy. Current recommendations made by the National Heart, Lung, and Blood Institute endorse using oral rather than intravenous (IV) antihistamines to avoid the cumulative effect on sedation. Despite this guideline, IV diphenhydramine use is still prevalent in many hospitals that treat persons with SCD. We performed a retrospective, single-center, cohort study comparing rates of oversedation among patients who received IV and oral diphenhydramine for management of opioid-induced pruritus in a large SCD inpatient population. Patients with SCD VOC admitted to an urban hospital between June 1, 2016 to July 30, 2017 were included if they were ≥ 18 years old and received either IV or oral diphenhydramine for OIP. Exclusion criteria: Pregnancy, received Disclosures Osunkwo: Terumo BCT: Speakers Bureau; Prolog Pharmaceuticals LLC: Consultancy; Novartis Pharmaceuticals LLC: Consultancy, Speakers Bureau. Symanowski:Immatics: Other: Data Safety Monitoring Board; Eli Lily & Co: Other: Data Safety Monitoring Board; Boston Biomedical: Other: Data Safety Monitoring Board ; Five Prime Therapeutics: Other: Data Safety Monitoring Board .

There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype-guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily. Steady-state trough concentrations were obtained after 5 days, targeting 1.0-5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls (P

Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus. We investigated the impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on i.v. tacrolimus exposure and toxicity in adult patients receiving an allogeneic hematopoietic stem cell transplant for hematologic malignancies. Germline DNA was extracted from buccal swabs and genotyped for CYP3A4, CYP3A5, and ABCB1 polymorphisms. Continuous i.v. infusion of tacrolimus .03 mg/kg/day was initiated on day +5 post-transplant, and steady-state blood concentrations were measured 4days later. We evaluated the association between phenotypes and prevalence of nontherapeutic target concentrations (below or above 5 to 15 ng/mL) as well as tacrolimus-related toxicities. Of 63 patients, 28.6% achieved the target concentration; 71.4% were15ng/mL, which was more common in CYP3A4 intermediate/normal metabolizers (compared with rapid) and those with at least 1 ABCB1 C2677T loss-of-function allele (P.05). ABCB1 C2677T was significantly associated with concentrations15ng/mL (odds ratio, 6.2; 95% confidence interval, 1.8 to 23.6; P = .004) and tacrolimus-related toxicities (odds ratio, 7.5; 95% confidence interval, 1.6 to 55.2; P = .02). ABCB1 C2677T and CYP3A4 are important determinants of i.v. tacrolimus exposure, whereas ABCB1 C2677T also impacts tacrolimus-related toxicities in stem cell transplants.

Hemorrhagic cystitis (HC) is a common and important complication of allogeneic hematopoietic cell transplantation (HCT). Reactivation of BK virus is its most common cause. The more intense immunosuppressive regimens administered to recipients of grafts from alternative donors have been reported to account for the increased susceptibility to HC in this population. This study compares patients undergoing HCT with either a haploidentical donor or a matched related donor, all of whom received identical immunosuppression with a post-transplantation cyclophosphamide-based regimen. The incidence of HC was significantly higher in the patients receiving a haploidentical graft (P = .01). The higher incidence of HC in haploidentical graft recipients is therefore directly related to the inherent immune deficiency that follows HLA-mismatched transplantation, independent of the intensity of pharmacologic immunosuppression. This finding carries significant clinical impact for the prevention and treatment of HC in haploidentical graft recipients.

Data indicate reversal of immune dysfunction with active treatment; however, the precise contribution of specific immune effector and immune suppressor components to achieve a minimal residual disease (MRD) state and immunomodulatory drug–mediated immunomodulatory effects in multiple myeloma (MM) patients remains poorly understood. In this prospective proof-of-principle study we sought to determine the dynamic alterations in natural killer (NK), NK-T, and T cells, including maturation and activating/inhibitory repertoire associated with MRDpos versus MRDneg status after autologous stem cell transplantation (ASCT) and during lenalidomide-based maintenance therapy. Of the 46MM patients enrolled, 36 had bone marrow MRD assessment 60+ days post-ASCT, 30 had longitudinal blood immunotyping during maintenance (pretherapy and after cycles 1, 3, and 6), and 20 had both MRD assessment and longitudinal immunotyping. Multicolor flow cytometry was used for MRD and immunotyping. Although the absolute number of NK cells was significantly lower in patients with MRDpos response, phenotypically NK cells in these patients displayed higher expression of activating receptors KIRDS4 and decreased expression of inhibitory molecules NKG2A compared with the MRDneg group. Furthermore, we observed significantly lower frequencies of T cells displaying KIR3DL1 in MRDpos versus MRDneg patients. Longitudinal immunotyping during lenalidomide maintenance showed loss of mature NK effector function, augmentation of NK-T effector function, and acquisition of PD1 independent anergic state. Our findings also suggest skewing of T cells toward an exhausted state during the maintenance phase in MRDpos patients. Put together, these observations provide a distinctive signature for MRDneg and MRDpos groups. These data support exploration of immune profiling in prospective clinical trials according to MRD-defined responses to identify patients that may benefit from maintenance intensification/modification or maintenance withdrawal.

Aim: We evaluated the application and clinical impact of multi-gene pharmacogenetic testing in oncology palliative medicine. Patients & methods: In a single-arm pilot trial, cancer patients with uncontrolled pain were assessed in a palliative medicine clinic at baseline and received pharmacogenetic testing. Results were used as applicable up to the final visit (day 30). Pain scores, opioid prescribing, and use of pharmacogenetic test results were collected. Results: In 75 patients, the median baseline pain score was 7/10. Of 54 evaluable at the final visit, 28 required opioid modifications and 19 had actionable genotypes, mostly CYP2D6. Pain improvement (≥2-point reduction) was higher than historical data (56 vs 30%; p

Background Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early‐onset CRC remains undescribed. Materials and Methods Retrospective analysis of data from the National Cancer Database (NCDB) between 2004 and 2016 was conducted. We combined income and education to form a composite measure of SES. Logistic regression and χ2 testing were used to examine early‐onset CRC according to SES group. Survival rates and Cox proportional hazards models compared stage‐specific overall survival (OS) between the SES groups. Results In total, 30,903 patients with early‐onset CRC were identified, of whom 78.7% were White; 14.5% were Black. Low SES compared with high SES patients were more likely to be Black (26.3% vs. 6.1%) or Hispanic (25.3% vs. 10.5%), have T4 tumors (21.3% vs. 17.8%) and/or N2 disease (13% vs. 11.1%), and present with stage IV disease (32.8% vs. 27.7%) at diagnosis (p, The incidence of and mortality from early‐onset colorectal cancer (CRC) is on the rise. This article details the relationship between socioeconomic status and clinical outcomes of young adults with early‐onset CRC.

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms.

Background: Circulating tumor DNA (ctDNA) can be used as a non-invasive method to detect and quantify genomic alterations (GA) in blood. We evaluated the relationship between ctDNA features, radiographic disease progression (RDP) and progression-free survival (PFS) in patients (pts) with metastatic breast cancer (MBC). Methods: A retrospective analysis of 32 female MBC pts with plasma ctDNA tested prior to a radiology scan was performed. Plasma ctDNA tests were run by Inivata using a 36-gene panel for detecting point mutations, short insertions/deletions, and copy number variations. ctDNA features were tabulated for each pt and included number of genomic alterations (numGA), maximum mutant allele frequency (maxMAF), and sum of mutant allele frequency (sumMAF). Univariate and multivariable logistic regression (LR) models were used to explore ctDNA features associated with RDP. Univariate and multivariable Cox proportional hazards models were used to identify ctDNA features that were associated with PFS. All models included ctDNA features as continuous variables. Results: Frequency of subtypes were 38% HR+HER2-, 28% HR+HER2+, 28% triple-negative, and 6% HR-HER2+. 97% had prior chemotherapy; 92% of HR+HER2-negative pts had prior endocrine therapy. 20 of 32 samples (69%) had GAs. The most common GAs were TP53 (50%), ESR1 (25%), PIK3CA (19%), and GATA3 (9.4%). Median numGA was 1 (0-12); median maxMAF was 1.9 (0-65.5); median sumMAF was 2.2 (0-157.2). Univariate LR analysis identified numGA (p=0.025), maxMAF (p=0.034), and sumMAF (p=0.049) to be significantly associated with RDP; numGA (p=0.056) and maxMAF (p=0.109) were retained in the final multivariable LR model. Univariate Cox regression analysis showed that numGA (HR=1.32, p Conclusions: Blood ctDNA profiling contributes to the prediction of RDP and PFS in MBC pts. High number of alterations and high allele fraction of these alterations were associated with worse clinical outcomes. These data provide an overview of the ctDNA dynamics in treated MBC pts. Citation Format: Tan AR, Symanowski J, Kim EN, Hosking M, Morris CD, Plagnol V, Farhangfar CJ, Ersek JL. Association of circulating tumor DNA with clinical outcomes in metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-20-06.

Introduction: The treatment for RRMM in first relapse typically involves a triplet combination, with choice influenced by the type of treatment already received, and the initial response. Elotuzumab (Elo), an anti-SLAMF7 immunostimulatory monoclonal antibody, mediates plasma cell killing by activating signals in NK cells and via antibody-dependent cell-mediated cytotoxicity. Carfilzomib (K) and lenalidomide (R) can activate NK cells and enhance NK cell-mediated lysis, whereas dexamethasone (d) can potentiate these strong pro-inflammatory stimuli by altering NK cell activating receptor expression and by sensitizing T cells to anergy signaling. Here, we report the preliminary results of a phase II study of Elo in combination with KRd (Elo-KRd) for MM in first relapse [ClinicalTrials.gov Identifier: NCT03361306]. Methods: Patients with RRMM (biochemical and/or clinical) aged at least 18 years who had received one prior line of systemic therapy and had measurable disease were included. Patients refractory to bortezomib and/or R were eligible. Patients with plasma cell leukemia (PCL) were not excluded. Treatment consisted of 4 cycles of Elo-KRd Induction (Elo 10 mg/kg IV once weekly on days 1,8,15, 22; K 20/27 mg/m 2 IV on days 1,2,8,9,15,16 ;R 25 mg oral daily on days 1-21; d 28 mg oral and 8 mg IV once weekly on days 1,8,15, 22) repeated every 28 days, followed by Elo-R maintenance (Elo 10 mg/kg IV every 2 weeks on days 1,15 for cycles 1-2 then 20 mg/kg IV on day 1 of each cycle; R 15 mg or last tolerated dose oral on days 1-21), cycle 5 and beyond until progression or unacceptable toxicity The primary endpoint of the study was very good partial response or better (≥VGPR) after 4 cycles of induction therapy. Secondary endpoints included overall response rate (ORR), overall survival (OS), progression free survival (PFS), minimal residual disease (MRD) and safety. Results are summarized with frequencies and proportions for categorical data, including response, and descriptive statistics for continuous data. Median survival outcomes were estimated with Kaplan Meier methods. Results: A total of 15 patients were enrolled by the data cut-off of 04/23/2021. Median age was 64 (range, 46-74) years; 13% of patients were ≥70 years old. Patients were uniformly distributed within revised ISS stages I/II/III at time of diagnosis, 33.3% in each category. Six (40%) patients had high-risk features: 4 with chromosomal abnormalities [del17p, t(4;14) or t(14;16)], 1 primary PCL and 1 extramedullary MM (lymph nodes and muscles). Twelve (80.0%) were refractory to R, 5 (33.3%) were refractory to bortezomib, one (3.3%) had prior Daratumumab exposure, and 12 (80.0%) had undergone autologous stem cell transplantation. Twelve patients completed 4 cycles of Elo-KRd induction while 3 patients discontinued treatment (due to disease progression) prior to completing induction. At end of induction, the ORR was 66.7% including ≥VGPR in 33.3% (5/15), CR in 13.3%. Rate of ≥VGPR as best response during study was 53.3% (8/15), with an ORR of 80%. MRD-negative (10 -5) rate post-induction was 20% (3/15). After a median follow-up of 23.1 months (range, 3.8 to 38.6 months), the median PFS is 11.5 months (95% CI 1.9, 18), and median OS is not reached (95%CI 10.1, NA). Grade 3/4 treatment-emergent adverse events (TEAEs) occurring in ≥10% of patients were neutropenia (n=5), thrombocytopenia (n=3), hypophosphatemia (n=4), fatigue (n=3), thromboembolic event (n=2), and second neoplasms (n=1, renal cell carcinoma). Grade 3/4 infection rate was 13.3% (2/15). No patient discontinued treatment due to an adverse event. We intend to update the analysis of the study results at the meeting. Conclusions: Elo-KRd was well tolerated and demonstrated activity in this high-risk patient population comparable to other contemporary approved triplet combinations in this population. Disclosures Bhutani: Amgen, BMS, Takeda: Speakers Bureau; Sanofi: Consultancy; Janssen, MedImmune, Takeda, Celgene, BMS, Cerecor, Celularity: Research Funding. Atrash: Jansen: Research Funding, Speakers Bureau; AMGEN: Research Funding; GSK: Research Funding. Foureau: TeneoBio, Celgene: Research Funding; Cytognos: Honoraria. Paul: Janssen Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Speakers Bureau; Bristol Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months; Genentech: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Voorhees: AbbVie Inc, Bristol-Myers Squibb Company; Consulting Agreement: GlaxoSmithKline, Novartis, Oncopeptides: Other: Advisory Committee; Bristol-Myers Squibb Company.: Other: Data Safety & Monitoring. Usmani: Array BioPharma: Consultancy, Research Funding; Abbvie: Consultancy; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.

Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.

Introduction: The addition of elotuzumab (Elo), an anti SLAMF7 immunostimulatory antibody, to carfilzomib, lenalidomide and dexamethasone (KRd) can lead to synergistic anti-myeloma immune effects. Pre-clinical data showed that both Elo and KRd promote innate NK cell response and adaptive cytotoxic T cell response. Here we report longitudinal NK and T cell profiling data in relation to clinical response and MRD status in the context of an Elo-KRd Phase II study (NCT03361306). Methods: Patients with relapsed refractory multiple myeloma (RRMM) after first-line therapy who enrolled in this phase II study received treatment with 4 cycles of Elo-KRd induction followed by Elo-Rd maintenance. Peripheral blood (PB) specimens were collected pre-induction (n=15), after induction (n=14), and every other month during maintenance (n=10). Bone marrow (BM) aspirates were collected pre- and post-induction and at the time of CR confirmation. Minimal residual disease (MRD) was assessed by next-generation flow cytometry (MRD NGF, 10 -5 sensitivity) post-induction for patients achieving very good partial response or better (≥VGPR). PB and BM NK, CD4 and CD8 T cell subset distribution, activation and anergy status were assessed by flow cytometry. Longitudinal Elo-KRd immune modulatory effect was modelled by polynomial regression analyses. Wilcoxon signed rank tests were used for timepoints comparisons. Mann-Whitney U tests were used for response groups comparisons between. Population frequency data, among mononuclear cells, are presented as mean±SD unless otherwise noted. Results: We first investigated Elo-KRd immune modulatory activity during induction treatment. Immature / mature NK cell distribution in PB remained unaltered pre- and post-induction (iNK: 8.9±6.4 vs 8.6±3.5, p=0.808; mNK: 14.9±6.8 vs 13.1±6.1, p=0.463). No significant change in PB NK activation markers KIR2DS4, KIR3DL1, NKG2A, NKG2D or NKp46 was observed throughout Elo-KRd induction. A lack of NK cell maturation was also observed in the BM despite a rise of iNK NKG2D expression (iNK NKG2D+: 22.5±7.7 vs 30.1±8.8, p=0.0.039). The number of both PB effector T helper (CD4+ Th) and cytotoxic T cell (CD8+ CTL) significantly decreased post-induction (PB ThEff: 28.5±16.4 vs 14.4±10.6, p Conclusions: Unlike preclinical data where Elo has shown to enhance NK cell activity, longitudinal immune profiling analysis in patients with RRMM treated with Elo-KRd revealed limited activation of NK cell and no effect on NK cell maturation. Instead, we noted several changes within T cell compartment, notably activation and subsequent loss of Th and CTL effector cells, along with gain of central memory phenotype. This observation was most apparent for patients achieving ≥VGPR who exhibited significant higher rate of Effector to CM T cell conversion. On relapse, CM CTL cell frequency in both PB and BM compartments decreased to baseline level. Taken together, our results suggest that higher CM conversion rate, typically associated with sustained antigen stimulation, was associated with response to study treatment. Disclosures Foureau: Cytognos: Honoraria; TeneoBio, Celgene: Research Funding. Bhutani: Amgen, BMS, Takeda: Speakers Bureau; Sanofi: Consultancy; Janssen, MedImmune, Takeda, Celgene, BMS, Cerecor, Celularity: Research Funding. Atrash: GSK: Research Funding; AMGEN: Research Funding; Jansen: Research Funding, Speakers Bureau. Paul: Regeneron: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Speakers Bureau; Bristol Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months. Symanowski: Eli Lilly: Consultancy, Other: DSMB Member; Immatics: Consultancy, Other: DSMB Member; Carsgen: Consultancy. Voorhees: Bristol-Myers Squibb Company.: Other: Data Safety & Monitoring; AbbVie Inc, Bristol-Myers Squibb Company; Consulting Agreement: GlaxoSmithKline, Novartis, Oncopeptides: Other: Advisory Committee. Usmani: EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; Abbvie: Consultancy; GSK: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; SkylineDX: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding.

Background: Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in adults. Venetoclax, an orally administered B-cell lymphoma 2 (BCL2) inhibitor, is a FDA approved therapy offering durable responses. Due to risk of tumor lysis syndrome (TLS) upon venetoclax initiation, a strict dose escalation schedule with frequent laboratory monitoring is recommended in the package insert (PI). Real world data reflecting adherence to this schedule and frequency of interventions resulting from intense monitoring are not described. Methods: Retrospective review of the Levine Cancer Institute database identified 73 consecutive patients with CLL who were initiated on venetoclax between July 2017 and March 2021. This included those initiated at the central academic site and regional academic-hybrid community sites. In the first two weeks of venetoclax, ramp up dosing and TLS labs (creatinine, potassium, calcium, phosphorous and uric acid) were evaluated for compliance consistent with the PI. Compliance required labs to be performed pre-dose, and at 6-8 hours and 24 hours after the initial 20 mg and 50 mg doses on weeks 1 and 2. The consequent interventions within these first 2 weeks, based on TLS labs, were then recorded. Patients who strictly adhered to all these laboratory checks at the various timepoints were considered compliant. Those who missed even a single lab or time point were considered non-compliant. Tumor lysis was measured by standard criteria using the Cairo-Bishop definition. The following Interventions were recorded: rasburicase administration, renal replacement therapy, ED visits, unplanned hospitalizations, ICU admissions, unplanned administration of IV fluids, the use of calcium supplementation, phosphate binders, treatment for hyperkalemia, dose reduction or holding of venetoclax. Baseline patient, disease, and treatment characteristics were summarized and described; rates of compliance were compared between tumor burden categories using Fisher's Exact test. Results : Baseline characteristics of the 73 identified patients were: 64% male, 79% white and 19% black, median age at venetoclax initiation was 67 (44 - 84). There were 49% of patients in the low tumor burden category, 44% in the medium tumor burden category and 6% in the high tumor burden category. Compliance with TLS labs during the first 2 weeks was 66% overall (n=48), with compliance between the tumor burden categories being 75% in high, 66% in medium and 67% in low (P>0.99). Interventions occurred in 6 (8%) of the patients, with all interventions occurring in the medium or high tumor burden group. These interventions included administration of IV fluids (n=2), calcium supplementation (n=1), phosphate binders (n=2) and holding of venetoclax (n=1). None of these 6 patients requiring an intervention had clinical or laboratory TLS. None of the 73 patients required rasburicase administration, renal replacement therapy, ED visits, unplanned hospitalizations, or ICU admissions during this 2 week ramp up period. Of the 6 patients requiring interventions, 4 patients had TLS labs performed by the PI versus 2 patients who did not. Clinical and laboratory TLS in the PI-compliant group was recorded. None of these patients had clinical TLS and 1 patient met the criteria for laboratory criteria TLS based on a 25% change from baseline in phosphorus and uric acid, however, labs remained in normal range. There were no deaths during the venetoclax ramp up. Conclusion: Compliance with the strict TLS lab monitoring during venetoclax initiation is not universal, likely due to real world patient and institutional barriers. The intervention rates during the first 2 weeks were low, with no patients in the low tumor burden category requiring an intervention. These results suggest that a less strict laboratory monitoring schedule may be safe in patients with low tumor burden CLL. If the safety is confirmed prospectively, it would make the venetoclax initiation less cumbersome and result in increased access to venetoclax for patients with low burden CLL. Disclosures Hu: Kite: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; Cellectar: Membership on an entity's Board of Directors or advisory committees. Moyo: Seattle Genetics: Consultancy. Park: Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; G1 Therapeutics: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Takeda: Research Funding. Copelan: Amgen: Consultancy. Avalos: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMJ Best Practice: Patents & Royalties: Royalties from a co-authored article on evaluation of neutropenia. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Jacobs: AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Research Funding, Speakers Bureau; Verastem: Consultancy; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; MEI Pharma: Research Funding; TeneoBio: Research Funding; SecuraBio: Consultancy, Speakers Bureau; Genentech: Consultancy; Jannsen: Speakers Bureau. Ghosh: Genmab: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; AbbVie: Honoraria, Speakers Bureau; Karyopharma: Consultancy, Honoraria; Genentech: Research Funding.

Purpose Stereotactic radiosurgery (SRS) dose is limited by brain metastasis (BM) size. The study goal was to retrospectively determine whether there is a benefit for intracranial outcomes and overall survival (OS) for gross total resection with single-fraction SRS versus SRS alone for patients with large BMs. Methods and Materials A large BM was defined as ≥4 cm3 (2 cm in diameter) prior to the study. We reviewed the records of consecutive patients treated with single-fraction SRS alone or surgery with preoperative or postoperative SRS between 2005 and 2013 from 2 institutions. Results Overall, 213 patients with 223 treated large BMs were included; 66 BMs (30%) were treated with SRS alone and 157 (70%) with surgery and SRS (63 preoperatively and 94 postoperatively). The groups (SRS vs surgery and SRS) were well balanced except regarding lesion volume (median, 5.9 cm3 vs 9.6 cm3; P Conclusions In this retrospective study, gross total resection with SRS was associated with significantly reduced LR compared with SRS alone for patients with large BMs. Postoperative SRS was associated with the highest rate of RN. Surgical resection with SRS may improve outcomes in patients with a limited number of large BMs compared with SRS alone. Further studies are warranted.

Background: Financial toxicity (FT) is defined as financial distress as a result of disease or treatment decisions. FT might be considered analogous to physical toxicity. Patients with high risk hematologic malignancies represent an especially vulnerable group for cost related issues due to heavy healthcare utilization, high costs associated with their treatment, and the potentially deadly consequences of treatment noncompliance. We hypothesized that comprehensive intervention on the financial aspects of care for these patients would lead to decreased mortality. Methods: All patients seen in Leukemia Clinic at the Levine Cancer Institute, a tertiary hospital-based specialty practice, were surveyed prior to their visit over a six-month period. All patients were aged ≥18 years and diagnosed with a high-risk hematologic malignancy (intermediate/high risk AML, high risk ALL, high or very high risk MDS, blast phase CML, or mixed phenotypic acute leukemia). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 5 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Patients who met these criteria were entered into the interventional cohort and scheduled for comprehensive intervention based on availability of study staff. Scheduling was done anonymously and without prioritization of perceived need. The intervention consisted of a nurse navigator visit where patients completed a standardized worksheet to identify gaps in care and opportunities for grant funding/other assistance, a clinical pharmacist visit for medication copay review and discussion of assistance programs, and the services of a community pro-bono financial planner for assistance with budgeting, asset management, and general financial advice. Demographic/clinical data were abstracted from the medical record and patients were tracked longitudinally for clinical outcomes. Categorical factors were summarized with proportions and compared between groups with Fisher's exact tests, while continuous factors were summarized with medians and compared between groups with median two-sample tests. Overall survival (OS) was evaluated with Kaplan Meier methods and compared between groups with a log rank test. Cox proportional hazards models were utilized in model selection procedures for OS. Individual prognostics were identified with univariable models, then backward elimination and forward selection (entry/elimination criteria p = 0.10) were carried out to identify a final base model. This was utilized to estimate an adjusted HR for the intervention variable. Results: A total of 105 patients met criteria and were placed in the interventional cohort with the intention to receive the full intervention. Of these patients, 59 (56.2%) were able to be scheduled and receive the full intervention, while the remainder received standard care only. There were no significant differences between the groups when compared by gender, race, age, marital status, insurance type, FT screening score, therapy received, or disease type (Table 1). OS was significantly different between the two groups, with a mortality rate during the study period of only 27% for the patients that received the full FT intervention as opposed to 43% for the patients who received standard care. Adjusted OS at 6 months for the interventional cohort was 81.4% (95% CI 68.9%-89.2%) versus 73.9% (95% CI 58.7%-84.3%) for the non-intervention group; OS rates at 12 months were 73.0% (59.0%-82.9%) and 46.4% (28.9%-63.8%), respectively (Figure 1). On univariate analysis, intervention was significantly associated with survival (HR: 0.44, 95% CI: 0.22 - 0.86, p = 0.017). After adjusting for insurance, race, and age at survey, risk of death in those receiving the intervention was 0.47 times the risk of death in those without the intervention (95% CI: 0.23 - 0.98, p = 0.043). Conclusions: High risk hematologic malignancy patients are at high risk for increased complications due to financial concerns. Intervening on FT in a comprehensive way including navigators, pharmacists, and financial counselors is effective and leads to decreased mortality. Disclosures Knight: Foundation for Financial Planning: Research Funding. Ai:Incyte: Speakers Bureau; Celgene: Speakers Bureau. Chojecki:Incyte: Research Funding; Novartis: Other: Investigator Meeting Attendance. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Grunwald:Pfizer: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Cardinal Health: Consultancy; Incyte: Consultancy, Research Funding; Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Merck: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Janssen: Research Funding; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Genentech/Roche: Research Funding; Premier: Consultancy; Premier: Consultancy; Amgen: Consultancy; Cardinal Health: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; Merck: Research Funding; Janssen: Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Pfizer: Consultancy; Pfizer: Consultancy; Merck: Consultancy; Amgen: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy.

Background Studies combining Daratumumab with a proteasome inhibitor and/ or an immunomodulatory drug have shown to increase the duration and depth of response in patients with newly diagnosed multiple myeloma (NDMM). While assessment of minimal residual status (MRD) after different stages of treatment is increasingly being evaluated in clinical trials as sensitive measure of depth of response and improved survival, published data on its utility as a tool to select the optimal post-induction therapy are not yet available. Study Design This ongoing single arm, two-stage, Phase II trial is designed with the primary objective to evaluate the efficacy in terms of rate of ≥ CR after 8 cycles of Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (Dara + KRd) induction therapy in patients with NDMM. Induction treatment cycles consist of daratumumab per standard dosing, carfilzomib 56 mg/m2 IV days 1,8,15 (per latest amendment), lenalidomide 25 mg PO days 1-21 and dexamethasone 40 mg PO/IV days 1,8,15,22 repeated every 28 days. After induction, all subjects will undergo disease evaluation. Those who experience ≥very good partial response (VGPR) will undergo an assessment of MRD and will be classified as MRD(+) or MRD(-) as determined by next generation sequencing at 10-5 sensitivity (clonoSEQ®, Adaptive Biotechnologies), with further therapy guided by MRD-based algorithm (Figure). Those with Study Population and Endpoints Eligible patients ≥ 18 years have NDMM requiring treatment, ECOG performance status 0-2, LVEF ≥45%, and creatinine clearance ≥ 30 mL/min. One prior cycle of systemic therapy is permitted to accommodate patients who needed emergent treatment at the time of diagnosis. Major exclusion criteria include non-secretory MM, active involvement of the central nervous system by MM, POEMS syndrome and severe COPD. Primary endpoint is CR or better after 8 cycles of Dara + KRd induction therapy. Secondary endpoints include PFS, OS, time to disease progression, overall response rate, duration of response, time to next treatment, and post-induction rate of MRD(-) response. Statistical Considerations A minimax 2-stage design will be used to test the hypothesis that the CR or better rate is ≤ 50%. Twenty-three subjects will be enrolled in the first stage, and if at least 12 of the 23 subjects have a CR or better after induction therapy, an additional 16 subjects will be enrolled (a total of 39 patients). If at least 24 of 39 subjects have a CR or better, the null hypothesis will be rejected. Based on a one-sided alpha = 0.10 significance level, this sample size will provide 90% power to reject the null hypothesis, assuming the true CR or better rate is 70%. Bayesian based stopping rules (Grade 3+ cardiovascular/pulmonary-related toxicities or any Grade 5 events) were developed that will be utilized for safety monitoring during induction phase of the study. Correlatives Beyond the direct anti-MM plasma cell activity, the Dara + KRd combination has a potent effect on immune effector cells and overall inflammation. Correlative aims include assessing blood and bone marrow immune biomarkers at baseline and during treatment for association with patient outcome. Mononuclear cells, isolated from peripheral blood samples and bone marrow aspirate will be obtained for NK, NKT, B and T cell immunotyping (including expression of activating/ inhibitory molecules and maturation status), T cell (αβ and γδ) clonotyping and chemokine-profiling. Additionally, MRD testing will be done by next generation flow cytometry (MRD-NGF) at 10-6 sensitivity. The study is actively recruiting at Levine Cancer Institute, Charlotte. At the time of submission, 8 subjects have enrolled and are in induction phase of treatment. Clinical trial information: ClinicalTrials.gov Identifier NCT04113018 Disclosures Bhutani: Janssen: Research Funding; BMS: Research Funding; MedImmune: Research Funding; Sanofi Genzyme: Consultancy. Atrash:Levine Cancer Institute, Atrium Health: Current Employment; Amgen, GSK, Karyopharm.: Research Funding; BMS, Jansen oncology, Sanofi: Speakers Bureau; Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria. Paul:Bristol-Myers Squibb: Other: Stock Ownership (prior employee); Regeneron: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau. Friend:Takeda: Speakers Bureau. Symanowski:Immatics: Consultancy; Casgen: Consultancy; Eli Lilly: Consultancy; Novartis: Consultancy. Voorhees:Oncopeptides: Honoraria, Other: Other relationship; Adaptive Biotechnologies: Honoraria, Other: Other relationship; TeneBio: Honoraria, Other: Other relationship; Janssen: Honoraria, Other: Other relationship; Novartis: Honoraria, Other: Other relationship; GSK: Honoraria, Other: Other relationship; BMS/Celgene: Honoraria, Other: Other relationship. Usmani:Celgene: Other; Array Biopharma: Research Funding; Pharmacyclics: Research Funding; Incyte: Research Funding; GSK: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding.

Background: In multiple myeloma, induction therapy (IT) before hematopoietic progenitor cells (HPC) collection reduces the tumor burden, improves the quality of the collection, and diminishes end-organ damage. The data concerning the impact of the response to IT on progression-free survival (PFS) after autologous stem cell transplant (ASCT) remains limited. IFM 2005-01 reported better PFS in patients who achieved at least a very good partial response (VGPR) after IT (PFS post-ASCT 41 vs. 31 months, p= 0.01). Also, studies have consistently shown that minimal residual disease (MRD) negativity impacted PFS/ overall survival (OS). Currently, rates of CR and MRD-negativity post-ASCT are sub-optimal. Given the clinical activity and the safety profile of daratumumab (Dara), evaluation of this novel agent pre- and post-ASCT is warranted, as it may improve the post-ASCT ≥ CR and MRD-negativity rates. Study Design and Methods: This study is a single-arm, two-stage phase II trial to estimate the CR rate post-ASCT in newly diagnosed MM (NDMM). Transplant eligible (TE) NDMM subjects who did not achieve at least a VGPR post initial IT are eligible for the trial. Enrollment will be planned post-induction and before HPC mobilization. Subjects will receive four weekly doses of Dara prior to HPC mobilization, then another four weekly doses of Dara after HPC engraftment post-ASCT. The primary objective is to evaluate the ≥ CR rate post-ASCT in NDMM subjects who did not achieve at least a VGPR post-induction. The secondary objectives are to estimate: ≥VGPR rate, time to first response (TTFR), time to best response (TTBR), duration of response (DoR), PFS, time to progression (TTP), time to next treatment (TTNT), and OS. Also, the study will evaluate toxicities related to Dara and ASCT outcomes (HPC collection and engraftment parameters). The exploratory objectives are to explore: MRD rates of bone marrow and HPC product using Euro-flow criteria and DNA-PCR.The correlation between systemic immune profiling and the clinical response using cytokine profiling by multiplex protein assay and Blood immunotyping [including NK, NK-T, and T cell subsets distribution and activation analyses by flow cytometry.The correlation between circulating T cell receptor (TCR) repertoire immuno-sequencing by next-generation sequencing (NGS) with clinical response parameters.The changes in BM and BM plasma cells' biology before and after treatment by Whole Exome Sequencing, andThe correlation between PET/CT responses and endpoint. The main eligibility criteria are age ≥ 18 years, ECOG PS 0-2, measurable disease at the time of diagnosis, < VGPR per IMWG 2016 criteria following a 3-drug IT regimen for TE-NDMM. However, patients must have achieved at least a minimal response, and treatment plan includes ASCT post-induction. Statistical methods: Post-ASCT ≥CR response is the primary endpoint for this study. For NDMM, standard therapy strategies provide ≥CR rates of approximately 50%. For this population of subjects treated with Dara-based in vivo purging, the aim is to achieve a post-ASCT ≥ CR rate of 70%. A minimax 2-stage design will be used to test the hypothesis that the ≥ CR rate post-ASCT is less than or equal to 50%. Twenty-three subjects will be enrolled in the first stage, and if at least 12 of the 23 subjects have ≥CR after ASCT, an additional 16 subjects will be enrolled (total of 39 subjects). If at least 24 of 39 subjects have ≥CR after ASCT, the null hypothesis will be rejected. Based on a one-sided, α = 0.10 significance level, this sample size will provide 90% power to reject the null, assuming the true ≥CR rate post-ASCT is 70%. The treatment schedule: Pre-mobilization Dara on days 1,8,15,22. Four weeks after the Day 22 dose of Dara, all subjects will undergo HPC mobilization with the hematopoietic growth factor G-CSF with or without the chemokine receptor type 4 (CXCR4) antagonist. Post-ASCT and after engraftment is complete, Dara will be restarted days +49, +56, +63, +70. ClinicalTrials.gov Identifier: NCT04230031 Figure 1 Disclosures Atrash: Amgen, GSK, Karyopharm.: Research Funding; Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria; BMS, Jansen oncology, Sanofi: Speakers Bureau. Paul:Regeneron: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Other: Stock Ownership (prior employee). Symanowski:Casgen: Consultancy; Eli Lilly: Consultancy; Immatics: Consultancy; Novartis: Consultancy. Bhutani:Janssen: Other: Clinical Trial Funding to Institute; BMS: Other: Clinical trial funding to institute, Speakers Bureau; Amgen: Speakers Bureau; Prothena: Other: Clinical Trial Funding to Institute; Sanofi Genzyme: Consultancy; Takeda: Other: Clinical trial funding to institute, Speakers Bureau; MedImmune: Other: Clinical Trial Funding to Institute. Voorhees:Bristol-Myers Squibb: Other: Personal fees; Celgene: Other: Personal fees; Janssen: Other: Personal fees; Novartis: Other: Personal fees; Oncopeptides: Other: Personal fees; TeneoBio: Other: Personal fees; Levine Cancer Institute, Atrium Health: Current Employment; Adaptive Biotechnologies: Other: Personal fees. Usmani:Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.

PURPOSE: Approximately 30% of patients with cancer who have pain have symptomatic improvement within 1 month using conventional pain management strategies. Engaging clinical pharmacists in palliative medicine (PM) and use of pharmacogenomic testing may improve cancer pain management. METHODS: Adult patients with cancer with uncontrolled pain had baseline assessments performed by PM providers using the Edmonton Symptom Assessment Scale. Pharmacotherapy was initiated or modified accordingly. A subset of patients consented to pharmacogenomic testing. The first pharmacy assessment occurred within 1 week of baseline and a second assessment was done within another week if intervention was required. Each patient’s final visit was at 1 month. Pain improvement rate (a reduction of two or more points on a 0-to-10 pain scale) from baseline to final visit was compared applying the Fisher exact test to published historical control data, and between patients with and without pharmacogenomic testing. Multivariate logistic regression identified pain improvement covariates. RESULTS: Of 142 patients undergoing pharmacy assessments, 53% had pain improvement compared with 30% in historical control subjects ( P < .001). Pain improvement was not different between those who received (n = 43) and did not receive (n = 99) pharmacogenomics testing (56% v 52%; P = .716). However, of 15 patients with an actionable genotype, 73% had pain improvement. Higher baseline pain (odds ratio [OR], 1.79; 95% CI, 1.43 to 2.24; P < .001), black or other race (OR, 0.42; 95% CI, 0.18 to 0.95; P = .04), and performance status 3 or 4 (OR, 0.18; 95% CI, 0.04 to 0.83; P = .03) were associated with odds of pain improvement, but pharmacogenomic testing was not ( P = .64). CONCLUSION: Including pharmacists in PM improves pain management effectiveness. Although pharmacogenomics did not statistically improve pain, a subset of patients with actionable genotypes may have benefited, warranting larger and randomized studies.

Background and objectives Stage IV colorectal cancer is often treated with palliative chemotherapy with the primary tumor in place. Low rates of unplanned surgical intervention (due to obstruction or perforation) have been reported. We examined a large national dataset to determine the rate of unplanned surgical intervention in these patients. Methods Surveillance Epidemiology and End Results-Medicare were queried for patients with metastatic colorectal cancer receiving chemotherapy (1998-2013). Patient who underwent planned surgery to the primary or metastasectomy were excluded. The primary outcome was the need for nonelective surgery. Time to surgery or death was measured. Conditional analyses were performed to determine the risk of surgical intervention at 6-month, 1-, and 2-year after diagnosis. Results The analytic cohort consisted of 4692 patients (median age = 75). At 24 months, 80% of the patients had died. The overall unplanned intervention rate was 12%. The probability of requiring unplanned surgery between 6 and 12 months was 8.1%; 12 and 24 months = 6.7%, and >24 months = 5.3%. Males, those with right-sided tumors, and older patients were less likely to require surgery. Conclusions Patients treated with palliative chemotherapy who are not resected upfront are unlikely to require unplanned surgery. Prophylactic surgery to reduce the risk of perforation or obstruction may not be necessary.

Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC).Immunohistochemistry for AURKA and AURKB was performed on pretreatment diagnostic transurethral resection of bladder tumor (TURBT) and matched cystectomy specimens in 50 subjects with MIBC who received NAC. Receiver operator characteristic curves (ROC) were calculated to assess the impact of AURKA and AURKB expression on pathologic response rate. Kaplan-Meier techniques and Cox proportional hazards models were used to assess the association with relapse-free survival (RFS) and overall survival (OS).Twenty-two of 50 [44%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.57, P = 0.46) nor AURKB (ROC = 0.56, P = 0.87) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort was associated with an inferior RFS, (HR = 3.88, P = 0.008) and OS, (HR = 6.10, P0.001). Similar trends for worse survival outcomes were also observed for high AURKB levels (RFS, [HR = 2.2, P = 0.13] and OS, (HR = 2.25, P = 0.09).High baseline tumor AURKA and AURKB expression identified MIBC patients with inferior RFS and OS despite the use of NAC and may identify patients who should be prioritized for clinical trial enrollment rather than standard cisplatin-based chemotherapy.