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Key Points Ofatumumab with glucocorticoid therapy for cGVHD resulted in 62.5% ORR at 6 months and 53% FFS at 12 months.Safety was observed with ofatumumab plus glucocorticoid for initial therapy., Visual Abstract, Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01680965.

Post-transplantation cyclophosphamide (PTCy) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (allo-HCT) across various donor types. However, immune reconstitution and infection incidence after PTCy-based versus conventional GVHD prophylaxis has not been well studied. We evaluated the infection density and immune reconstitution (ie, absolute CD4+ T cell, CD8+ T cell, natural killer cell, and B cell counts) at 3 months, 6 months, and 1 year post-HCT in 583 consecutive adult patients undergoing allo-HCT with myeloablative (n = 223) or reduced-intensity (n = 360) conditioning between 2012 and 2018. Haploidentical (haplo; n = 75) and 8/8 HLA-matched unrelated (MUD; n = 08) donor types were included. GVHD prophylaxis was PTCy-based in all haplo (n = 75) and in 38 MUD allo-HCT recipients, whereas tacrolimus/methotrexate (Tac/MTX) was used in 89 and Tac/Sirolimus (Tac/Sir) was used in 381 MUD allo-HCT recipients. Clinical outcomes, including infections, nonrelapse mortality (NRM), relapse, and overall survival (OS), were compared across the 4 treatment groups. The recovery of absolute total CD4+ T-cell count was significantly lower in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups throughout 1 year post-allo-HCT (P = .025). In contrast, CD19+ B-cell counts at 6 months and thereafter were higher in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups (P

Background Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored. Methods Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling. Results Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19). Conclusions The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered. Lay summary The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.

Objectives The majority of patients with acute myeloid leukemia (AML) are aged 70 and over. However, there is uncertainty about how and whether older patients with AML should receive cytotoxic treatment. Materials and methods Medline and Cochrane library search was performed for studies in newly diagnosed AML which enrolled at least 20 patients per arm (for randomized controlled trials), or 50 patients (for non-randomized studies) over the age of 70. References were hand searched for additional eligible studies. Study investigators were contacted to maximize relevant data. Dual independent data extraction was done using standardized data collection forms. Data was collected on study and treatment characteristics, baseline patient information, and outcomes. Study methodological quality was assessed. The primary outcome was 1 year overall survival (OS). Impact of treatment [intensive chemotherapy (INT), low-dose chemotherapy (LOW), hypomethylating agents (HMA), or best supportive care (BSC)], cytogenetics, performance status, and comorbidity were assessed. Results The search produced 11,846 references of which 38 randomized controlled trials and 30 non-randomized studies met inclusion criteria, representing 13,381 patients, with a worldwide distribution. One-year OS with INT was 37% (31–42%), with LOW 11% (6–18%), with HMA 35% (18–54%) and with BSC 17%(13–21%). Two-year OS was 22% (18–26%), 11% (7–15%), 22% (16–28%), 6% (2–12%), respectively. We present subgroup data based on the studies including cytogenetics, performance status, and comorbidity. Formal direct comparisons with adjustment for all prognostic factors were not possible. Conclusions In this largest to date series of AML patients aged 70 and older, we provide benchmarks for treatment efficacy and effectiveness that may be used for decision analysis models and for the future development of clinical trials focusing on these patients.

Background Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi-institutional phase 2 study. Methods Patients with BTC who progressed on at least 1 line of systemic therapy received regorafenib at 160 mg daily for 21 days on and 7 days off. The primary endpoint was 6-month overall survival (OS), and the secondary endpoints were median OS, progression-free survival (PFS), and objective response rates. Pretreatment plasma was collected for cytokine evaluation. Results A total of 39 patients were enrolled, and 33 were evaluable for efficacy. The median PFS and OS were 3.7 and 5.4 months, respectively, with survival rates of 46.2% at 6 months, 35.9% at 12 months, and 25.6% at 18 months for the intention-to-treat population. For the 33 evaluable patients who received regorafenib for at least 3 weeks, the median PFS and OS were 3.9 and 6.7 months, respectively, with survival rates of 51.5% at 6 months, 39.4% at 12 months, and 27.3% at 18 months. The objective response rate was 9.1%, and the disease control rate was 63.6%. Twenty-eight patients (71.8%) experienced grade 3/4 adverse events. Among the 23 cytokines analyzed, elevated baseline vascular endothelial growth factor D (VEGF-D) was associated with shorter PFS, whereas elevated baseline interleukin 6 (IL-6) and glycoprotein 130 (GP130) were associated with shorter OS. Conclusions Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to identify a group of patients with BTC who may benefit from regorafenib.

Older women have a worse prognosis with advanced epithelial ovarian cancer (EOC) and comorbidities likely contribute to poor outcomes. We sought to identify comorbid conditions and treatment-related factors in older women.A retrospective chart review identified 351 patients who underwent cytoreductive surgery (CRS). 100/351 (28.5%) were ≥ 70 years old. Demographic and clinicopathologic information was collected. Crude progression-free (PFS) and overall survival (OS) estimates were calculated using Kaplan-Meier method. Cox proportional hazards regression model was used to estimate hazard ratios and adjustments for confounders.Study subjects ≥70 years old had significantly: higher Cumulative Illness Rating Scale-Geriatric (CIRS-G) score (5.9 vs 4.3; p = 0.0001), less completion of adjuvant chemotherapy (24% vs 15.1%; p = 0.049), less intraperitoneal (IP) therapy (18.2% vs 35.5%; p = 0.002), less clinical trial participation (16% vs 26.3%; p = 0.040), decreased platinum sensitivity (60% vs 73.7%; p = 0.012) and lacked BRCA mutations (0% vs 12%; p = 0.0006). They were less likely to have optimal CRS (75% vs 86.9%; p = 0.007) with same surgical complexity (p = 0.89). Patients ≥70 had significantly worse PFS and OS. In a multivariate analysis, better OS was associated with younger age (70 years old), any IP therapy, completion of adjuvant chemotherapy, and platinum sensitivity.The older cohort had worse CIRS-G scores (5.9 vs 4.3; p = 0.0001), but no strong associations between comorbidities and treatment characteristics, but less optimal CRS rates (75% vs 86.9%; p = 0.007) with similar surgical complexity and less platinum sensitivity. Our results show comorbid conditions in older patients with advanced EOC may have less impact than tumor biology.

CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with ≥grade 3 neutropenia seen in 21 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were undetectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, seven severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.

Objective Big Data is widely seen as a major opportunity for progress in the practice of personalized medicine, attracting the attention from medical societies and presidential teams alike as it offers a unique opportunity to enlarge the base of evidence, especially for older patients underrepresented in clinical trials. This study prospectively assessed the real-time availability of clinical cases in the Health & Research Informatics Total Cancer Care™ (TCC) database matching community patients with cancer, and the impact of such a consultation on treatment. Materials and Methods Patients aged 70 and older seen at the Lynn Cancer Institute (LCI) with a documented malignancy were eligible. Geriatric screening information and the oncologist's pre-consultation treatment plan were sent to Moffitt. A search for similar patients was done in TCC and additional information retrieved from Electronic Medical Records. A report summarizing the data was sent and the utility of such a consultation was assessed per email after the treatment decision. Results Thirty one patients were included. The geriatric screening was positive in 87.1% (27) of them. The oncogeriatric consultation took on average 2.2 working days. It influenced treatment in 38.7% (12), and modified it in 19.4% (6). The consultation was perceived as “somewhat” to “very useful” in 83.9% (26). Conclusion This study establishes a proof of concept of the feasibility of real time use of Big Data for clinical practice. The geriatric screening and the consultation report influenced treatment in 38.7% of cases and modified it in 19.4%, which compares very well with oncogeriatric literature. Additional steps are needed to render it financially and clinically viable.

Objective Prior studies demonstrating minimal psychological consequences for women receiving genetic counseling/genetic testing (GC/GT) for hereditary breast and ovarian cancer rely on predominantly Caucasian women. We conducted a prospective follow-up of a subset of participants from a population-based study of Black breast cancer (BC) survivors receiving GC/GT for BRCA1 and BRCA2 mutations. Methods Black women with invasive BC at age ≤ 50 years diagnosed between 2009 and 2012 were recruited through the Florida Cancer Registry. Participants (n = 215, age M = 44.7, SD = 6.2) were offered telephone pre- and post-test GC, a subset completed questionnaires assessing sociodemographic, clinical, and psychosocial variables. Results There were no baseline differences in cancer-related distress, psychological distress, or quality of life between test result groups. Social well-being improved in women receiving negative results (P = .01), but no other outcomes demonstrated significant changes over time between groups. Conclusions Our study is among the first to demonstrate minimal negative psychosocial outcomes following GC/GT among young Black BC survivors, irrespective of test results.

BACKGROUND: Androgens were shown to play a key role in the growth and progression of pancreatic cancer. We evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel as a first-line treatment in advanced pancreatic cancer. METHODS: We used the standard 3 + 3 dose escalation design with cohort expansion to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg/day orally (phase 1a) in combination with gemcitabine and nab-paclitaxel in metastatic pancreatic cancer patients. In the expansion phase (phase 1b), AR+ was a pre-requisite criterion. We also evaluated the full pharmacokinetic (PK) profile for nab-paclitaxel and enzalutamide. RESULTS: We enrolled 24 patients, 12 patients in phase 1a and 12 patients in phase 1b. The median age was 68 (range, 32–84) years. No DLTs were observed. Grade 3/4 treatment related adverse events included neutropenia (44%), anemia (40%), leukopenia (24%), nausea and vomiting (20%), diarrhea (16%), infections (12%), thrombocytopenia (8%), thromboembolic event (8%), hypertension (8%), hypokalemia (8%), hyponatremia (8%), and ALT elevation (8%). Median overall survival and progression-free survival was 9.73 [95%CI:9.73–13.5] and 7.53 (95%CI:6.05–12.8) months, respectively. PK analysis suggests that the combination therapy does not impact the kinetics of either drug evaluated. Enzalutamide reached steady-state levels between day 22 and 29 and the mean half-life of nab-paclitaxel was 19.6 ± 4.7 h. CONCLUSIONS: Enzalutamide 160 mg daily in combination with gemcitabine and nab-paclitaxel can be safely administered with no unexpected toxicities. We also noticed preliminary signals of efficacy with this combination.

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70–2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches. Electronic supplementary material The online version of this article (10.1007/s00262-018-2236-7) contains supplementary material, which is available to authorized users.

To date, most comorbidity studies have analyzed either a subgroup of frequent diseases, or used summary instruments such as the Charlson score or the Cumulative Illness Rating Scale-Geriatric (CIRS-G). Yet, comorbidity is a multidimensional construct and impacts function, treatment tolerance, and survival. We assessed how heat maps can unveil specific patterns of comorbidities associated with overall survival (OS) in older cancer patients treated with chemotherapy.We reviewed four trials that prospectively evaluated comorbidities using CIRS-G. Eligible patients were 65years or older and had solid tumors with 30 or more patients per tumor site. Heat maps were constructed based on CIRS-G scores and correlated with OS.Among 818 patients accrued, 399 were eligible: Median follow-up was 53.4months and median OS was 19.6months (95% CI: 16.5-24.2). In the univariate model for OS, patients with a severe CIRS-G score in 6 organ categories (3-4 in heart, hematopoietic, respiratory, and musculoskeletal-integument and 2-4 in upper GI and liver) had statistically worse OS than those with lower scores. According to a total risk score (TRS) based on hazard ratios for OS, OS of the low risk group (N=309, TRS2) was significantly higher (24.3m vs. 10.8m, HR=2.05, 95% CI: 1.58-2.66). TRS was a predictor for OS independently from stage, primary site, prior chemotherapy, ECOG performance status, and IADL (HR=1.94, 95% CI: 1.47-2.57).High TRS was a predictor of poor survival. Comorbidity heat maps appear promising to identify diseases most affecting the OS of older cancer patients.

Background Post-transplant cyclophosphamide (PTCY) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT) across various donor types. However, immune reconstitution after PTCY-based vs. conventional GVHD prophylaxis has not been well studied. Methods We evaluated the pace of immune reconstitution (CD4+ T-cell, CD8+ T-cell, NK-cell and B-cell) at 3 months, 6 months and 1 year post-HCT in 583 adult patients receiving myeloablative (n=223) or reduced intensity conditioning (n=360) HCT (2012-2018). Haploidentical (Haplo; n=75) and 8/8 HLA-matched unrelated (MUD, n=508) donor types were included. GVHD prophylaxis was PTCY-based in 75 Haplo and 38 MUD (MUD-PTCY) HCT, while tacrolimus/methotrexate (TAC/MTX) was used in 89 and TAC/Sirolimus (TAC/SIR) in 381 MUD HCT. Clinical outcomes including viral infections, non-relapse mortality (NRM) and overall survival (OS) were compared across all four treatment groups. Results The recovery of absolute total CD4+ T-cell count after Haplo-PTCY and MUD-PTCY was significantly lower compared to MUD TAC/MTX or MUD TAC/SIR throughout 1 year of HCT (Figure). In contrast, CD19+ B-cell recovery at 6 months and thereafter was more rapid after Haplo-PTCY and MUD-PTCY HCT in comparison to MUD TAC/MTX and MUD TAC/SIR. In subgroup analysis compared to MUD TAC/MTX HCT, total CD8+ T-cell or NK-cell recovery was not significantly different after Haplo-PTCY or MUD-PTCY HCT. However, patients receiving MUD TAC/SIR vs. MUD TAC/MTX had significantly slower reconstitution of total CD8+ T-cells up to 6 months and CD19+ B-cells at 1 year of HCT, but no significant differences in CD4+ T-cell or NK-cell recovery. The distribution of recipient CMV serostatus was similar in all four groups: 72% in Haplo-PTCY, 62 % in MUD-PTCY HCT, 68% in MUD TAC/MTX and 63% in MUD TAC/SIR (p=0.11). Cumulative incidence of CMV reactivation/infection at 1-year of HCT was higher in patients receiving Haplo-PTCY (39.6%) or MUD TAC-MTX (37.7%) compared to those receiving MUD-PTCY (27.0%) or MUD TAC/SIR (22.8%; p Conclusion Our data demonstrate that the pattern of immune reconstitution after HCT is different after PTCY-based vs. conventional GVHD prophylaxis with delayed total CD4+ T-cell but more rapid B-cell recovery after PTCY-based GVHD prophylaxis. The rates of CMV and EBV viral infections were different across the donor types. However, these differences had no significant influence on NRM or survival after HCT.

Systemic glucocorticoids remain the standard treatment for gastrointestinal (GI) acute graft-versus-host disease (aGVHD) despite their toxicity and incomplete efficacy. Controlled trials have tested poorly absorbable steroids as adjuncts with systemic glucocorticoids, but only small case series have reported treatment with poorly absorbed beclomethasone dipropionate (BDP) and budesonide (BUD) alone. Our team has adopted the practice of administering BDP or BDP+BUD without systemic glucocorticoids as first-line therapy for isolated upper GI (UGI) aGVHD. We report results in 76 patients treated with BDP alone and in 81 patients treated with BDP+BUD, with allocation by physician choice. Almost all patients received peripheral blood stem cells (92%) from a fully HLA-matched related or unrelated donor (80%) after myeloablative conditioning (76%) for acute leukemia (49%), myelodysplastic syndrome (17%), non-Hodgkin lymphoma (14%), or another hematopoietic disorders (20%). After 28 days of treatment with BDP, 46% of the patients had a complete response (CR) and 10% had a partial response (PR); after 200 days, 61 (80%) patients were alive, 34% maintained a CR, and 3% maintained a PR, whereas 53% required additional immunosuppression (IS). After 28 days of treatment with BDP+BUD, 67% had a CR and 10% a PR; after 200 days, 74 (91%) patients were alive, 46% maintained a CR, and 2% maintained a PR, whereas 43% required additional IS. Among the entire cohort of 157 patients, 66 (42%) were treated successfully without systemic glucocorticoids. This study reports the efficacy of poorly absorbable steroids alone for patients with isolated UGI aGVHD. Prospective trials should test for the potential advantages of BDP and BUD use over systemic glucocorticoids.

Background: Information about the frequency of cannabinoid use and the clinical characteristics of its users in oncology supportive care is limited. This study explored associations between cannabinoid use and cancer-related clinical characteristics in a cancer population. Patients and Methods: This retrospective review included 332 patients who had a urine drug test (UDT) for tetrahydrocannabinol (THC) together with completion of an Edmonton Symptom Assessment Scale (ESAS) and cannabinoid history questionnaire on the same day that urine was obtained during 1 year in the supportive care clinic. Results: The frequency of positive results for THC in a UDT was 22.9% (n=76). Significant statistical differences were seen between THC-positive and THC-negative patients for age (median of 52 [lower quartile, 44; upper quartile, 56] vs 58 [48; 67] years; PP=.034), and past or current cannabinoid use (65.8% vs 26.2%; PP=.001), nausea (1 [0; 3] vs 0 [0; 3]; P=.049), appetite (4 [2; 7] vs 3 [0; 5.75]; P=.015), overall well-being (5.5 [4; 7] vs 5 [3; 6]; P=.002), spiritual well-being (5 [2; 6] vs 3 [1; 3]; P=.015), insomnia (7 [5; 9] vs 4 [2; 7]; PP=.001). Among patients who reported current or past cannabinoid use, THC-positive patients had higher total scores and scores for pain, appetite, overall well-being, spiritual well-being, and insomnia than THC-negative patients. Conclusions: Patients with cancer receiving outpatient supportive care who had positive UDT results for THC had higher symptom severity scores for pain, nausea, appetite, overall and spiritual well-being, and insomnia compared with their THC-negative counterparts. These results highlight potential opportunities to improve palliative care.

Objective Breast cancer (BC) survivors with a genetic mutation are at higher risk for subsequent cancer; knowing genetic risk status could help survivors make decisions about follow-up screening. Uptake of genetic counseling and testing (GC/GT) to determine BRCA status is low among high risk BC survivors. This study assessed feasibility, acceptability, and preliminary efficacy of a newly developed psychoeducational intervention (PEI) for GC/GT. Methods High risk BC survivors (N = 119) completed a baseline questionnaire and were randomized to the intervention (PEI video/booklet) or control (factsheet) group. Follow-up questionnaires were completed 2 weeks after baseline (T2), and 4 months after T2 (T3). We analyzed recruitment, retention (feasibility), whether the participant viewed study materials (acceptability), intent to get GC/GT (efficacy), and psychosocial outcomes (eg, perceived risk, Impact of Events Scale [IES]). t tests or chi-square tests identified differences between intervention groups at baseline. Mixed models examined main effects of group, time, and group-by-time interactions. Results Groups were similar on demographic characteristics (P ≥ .05). Of participants who completed the baseline questionnaire, 91% followed through to study completion and 92% viewed study materials. A higher percentage of participants in the intervention group moved toward GC/GT (28% vs 8%; P = .027). Mixed models demonstrated significant group-by-time interactions for perceived risk (P = .029), IES (P = .027), and IES avoidance subscale (P = .012). Conclusions The PEI was feasible, acceptable, and efficacious. Women in the intervention group reported greater intentions to pursue GC, greater perceived risk, and decreased avoidance. Future studies should seek to first identify system-level barriers and facilitators before aiming to address individual-level barriers.

BACKGROUND: European LeukemiaNet (ELN) 2017 risk stratification by genetics is prognostic of outcomes in patients with acute myeloid leukemia (AML). However, the prognostic impact of the 2017 ELN genetic risk stratification after allogeneic hematopoietic cell transplantation (alloHCT) is not well established. OBJECTIVE: We examined the effect of 2017 ELN genetic risk stratification on alloHCT outcomes of AML. METHODS: We included 500 adult (≥18 years) AML patients in first (n=370) or second (n=130) complete remission receiving alloHCT from 2005 to 2016. Patients were classified into favorable (12%), intermediate (57%), and adverse (32%) 2017 ELN risk groups. The Cox proportional hazard model was used to conduct the multivariable analyses of leukemia-free survival (LFS) and overall survival (OS). Relapse and non-relapse mortality were analyzed by the Fine-Gray regression model. RESULTS: OS at 2 years was 72% in the favorable vs. 60% in the intermediate vs. 45% in the adverse risk groups (p

Introduction Mycophenolate mofetil (MMF) dose/kg can influence clinical outcomes of allogeneic hematopoietic cell transplantation (HCT) including acute graft-versus-host disease (GVHD) (Harnicar BBMT 2015; Bejanyan BBMT 2018). When used for GVHD prophylaxis in conjunction with post-transplant cyclophosphamide (PTCy), MMF is generally dosed at 15 mg/kg three times daily (capped at a maximum of 3 g/day) and combined with either tacrolimus or sirolimus. Thus, many adults receive the maximum dose and a variable dose/kg of MMF. Objectives We sought to investigate the impact of MMF dose/kg on clinical outcomes of HCT in the setting of PTCy-based GVHD prophylaxis, where the effect of MMF dose/kg is unknown. Methods Included are 112 consecutive adult patients with hematologic malignancies who received myeloablative (n=70) or reduced intensity (n=42) HCT at the Moffitt Cancer Center between 2012-2018 with T-cell replete peripheral blood stem cells (n=94) or bone marrow (n=18). GVHD prophylaxis consisted of PTCy/MMF and either tacrolimus (n=57) or sirolimus (n=55). MMF dose relative to patient actual body weight (mg/kg/day), was stratified by tertiles into low ( 40 mg/kg/day, n=36). Results The median age at transplant was 57.8 (range: 21-75) years. Median follow-up was 12 months (range: 0.3-39). Donors were haploidentical related (n=74), mismatched unrelated (n=26), and matched related/unrelated (n=12). MMF dose groups had similar characteristics, except the low dose group having a higher proportion of males (p Conclusion In patients receiving PTCy based GVHD prophylaxis, MMF dose/kg had no significant effect on GVHD. However, lower MMF dose/kg was associated with worse DFS. This study suggests that

556 Background: First line therapy for advanced cholangiocarcinoma (CCA) is currently gemcitabine and cisplatin. However, survival rarely exceeds one year with this regimen. PI3K/AKT activation has been shown to increase resistance to chemotherapy in CCA; therefore, inhibiting this pathway may improve chemotherapy’s efficacy. This phase II study evaluated the safety and efficacy of copanlisib, a potent and reversible pan-class I PI3K inhibitor, with gemcitabine and cisplatin in advanced CCA. Methods: Between July 2016 and April 2019, pts with histologically confirmed advanced/unresectable CCA received cisplatin (25 mg/m2), gemcitabine (1000mg/m2), and copanlisib 60mg on day 1 and 8, every 21 days as first line treatment. The primary endpoint was PFS at 6 months. Secondary endpoints were RR, median OS and PFS, and safety profile. A single-arm Simon’s two-stage minimax design with one-sided 10% type I error and 80% power was used. Based on ABC-01 and ABC-02 studies, PFS6 for gemcitabine and cisplatin were 57.1% and 59.3%, respectively. Therefore, PFS6 of 57% was considered not to warrant further study and ≥72% to warrant further investigation. Results: Twenty-four pts received at least one dose of the study drug (62.5% female, median age 64 years), with 70.8% intrahepatic, 16.7% extrahepatic, and 12.5% gallbladder cancer. For all pts, median OS was 13.9 months (95% CI: 6.8-17.9) and median PFS was 6.2 months (95% CI: 1.3-11.1). PFS at 6 and 12 months was 57.0% and 42.2%, and 6 and 12-month OS was 73.9% and 53.2%, respectively. Only 19 pts were considered evaluable for RR. Five pts were either lost to follow up, withdrew consent, or died before a second scan was done. Six pts achieved PR (31.5%) and 11 (57.9%) had SD. Grade 3 or higher adverse events (AE) occurred in 75% of pts. The most common grade 3/4 AEs were decreased neutrophil count (40%) and increased lipase (20%). Treated related AEs led to drug discontinuation for 3 pts (12.5%) and dose modification for 7 pts (29.2%). Conclusions: Gemcitabine, cisplatin, and copanlisib in combination did not meet the primary endpoint of 6-month PFS. However, additional correlative work is ongoing to identify a possible biomarker for copanlisib. Clinical trial information: NCT02631590.

PURPOSE: Uptake of genetic counseling among breast cancer survivors is low. We used the Health Belief Model (HBM) to explore factors associated with readiness for genetic counseling among breast cancer survivors. METHODS: Breast cancer survivors meeting NCCN genetic counseling referral criteria were recruited through clinics and community settings. Participants completed questionnaires capturing demographic and clinical information and factors guided by the HBM, including health beliefs, psychosocial variables, and cues to action. Using logistic regression, we examined whether the above variables differed based on readiness group (pre-contemplators, who did not plan to make a genetic counseling appointment, and contemplators, who planned to make a genetic counseling appointment in the next 1– 6 months). RESULTS: Of 111 participants, 57% were pre-contemplators and 43% were contemplators. In the multivariable model, higher cancer worry was associated with increased odds of being a contemplator (OR=2.99; 95% CI=1.37–6.54) and higher perceived barriers to genetic counseling were associated with decreased odds of being a contemplator (OR=0.31; 95% CI= 0.11–0.85). Those who reported a family member encouraged them to get tested were more likely to be contemplators (OR=3.57; 95% CI=1.19– 10.70). CONCLUSIONS: Our results suggest key factors for predicting genetic counseling readiness include cancer worry, perceived barriers, and family influence. IMPLICATIONS FOR CANCER SURVIVORS: Ideally genetic counseling occurs prior to treatment, but significant advantages exist for survivors. There is need for increased genetic counseling awareness. Better understanding of factors related to survivors’ decisions about counseling can inform tailored interventions to improve uptake and ultimately reduce cancer recurrence risk.

In older patients with acute myeloid leukemia, the more frequent presence of biologically inherent therapy-resistant disease and increased comorbidities translate to poor overall survival and therapeutic challenges. Optimal front-line therapies for older patients with acute myeloid leukemia remain controversial. We retrospectively evaluated survival outcomes in 980 elderly (≥70 years) acute myeloid leukemia patients from a single institution between 1995 and 2016. Four treatment categories were compared: high-intensity (daunorubicin/cytarabine or equivalent), hypomethylating agent, low-intensity (low-dose cytarabine or similar without hypomethylating agents), and supportive care therapy (including hydroxyurea). At a median follow up of 20.5 months, the median overall survival for the entire cohort was 7.1 months. Multivariate analysis identified secondary acute myeloid leukemia, poor-risk cytogenetics, performance status, front-line therapy, age, white blood cell count, platelet count, and hemoglobin level at diagnosis as having an impact on survival. High-intensity therapy was used in 360 patients (36.7%), hypomethylating agent in 255 (26.0%), low-intensity therapy in 91 (9.3%), and supportive care in 274 (28.0%). Pairwise comparisons between hypomethylating agent therapy and the three other treatment groups demonstrated statistically significant superior median overall survival with hypomethylating agent [14.4 months) vs. high-intensity therapy 10.8 months, hazard ratio 1.35, 95% confidence interval (CI): 1.10-1.65; P =0.004], low-intensity therapy (5.9 months, hazard ratio 2.01, 95%CI: 1.53-2.62; P

Background Studies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact. Methods We retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model. Results Median age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025–0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2–27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1–3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27–3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34–0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04–1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1–3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed. Conclusions In older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities.

In this study we developed 25 computed tomography descriptors among 117 patients with lung adenocarcinoma to semiquantitatively assess their association with overall survival. Pleural attachment was significantly associated with an increased risk of death and texture was most important for distinguishing histological subtypes. This approach has the potential to support automated analyses and develop decision-support clinical tools.Computed tomography (CT) characteristics derived from noninvasive images that represent the entire tumor might have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival.An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n = 117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that might differentiate histological subtypes.Characteristics significantly associated with overall survival included pleural attachment (P.001), air bronchogram (P = .03), and lymphadenopathy (P = .02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.53-6.70) and among patients with lepidic predominant adenocarcinomas (HR, 5.85; 95% CI, 1.75-19.59), and lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR, 3.07; 95% CI, 1.09-8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the 2 subtypes.A subset of the semiquantitative characteristics described herein has prognostic importance and provides the ability to distinguish between different histological subtypes of lung adenocarcinoma.

Background Black women are disproportionately affected with triple-negative breast cancer and have relatively poor survival. To the authors' knowledge, it is not known to what extent differences in the clinical presentation of breast cancer between non-Hispanic white women and black women can be accounted for by the presence of mutations in the BRCA1 and BRCA2 genes. The authors sought to evaluate the frequency of BRCA pathogenic variants in a population-based sample of young black women with breast cancer. Methods Black women diagnosed with invasive breast cancer at age ≤50 years from 2009 to 2012 were recruited to the study through the Florida Cancer Registry. Participants underwent genetic counseling, completed a study questionnaire, and consented to release of their medical records. Saliva specimens were collected for BRCA sequencing and large rearrangement testing through multiplex ligation-dependent probe amplification. Results A DNA sample was evaluated for 396 women, 49 of whom (12.4%) had a mutation in BRCA1 or BRCA2. Eight recurrent mutations accounted for 49% of all pathogenic variants. Conclusions To the authors' knowledge, the prevalence of BRCA mutations among the Florida-based sample of young black women with breast cancer in the current study exceeds that previously reported for non-Hispanic white women. It is appropriate to recommend BRCA testing in all young black women with invasive breast cancer.

Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (≥ 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27-60) for sirolimus/tacrolimus and 49 months (range 29-63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease. Further study of determinants of successful immune suppression discontinuation is needed.

Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n = 293) to MTX/TAC (n = 414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II–IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P = 0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI ⩾ 4 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14–3.04, P = 0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48–1.26, P = 0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II–IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI ⩾ 4.

PurposeBlack women are more likely to develop early-onset (≤50years) breast cancer (BC) and have the lowest five-year, cause-specific survival rate of any United States (U.S.) racial or ethnic group. These disparities can be attributed partially to the higher rate of triple-negative BC (TNBC) in Blacks. Yet, little is known about health-related quality of life (HRQOL) among Black women with TNBC.MethodsBlack women with invasive BC≤50years were recruited via the Florida Cancer Data System as part of a population-based case-only study of etiology and outcomes of early-onset invasive BC. Of 460 consented participants, a subset of 355 self-reported sociodemographic, clinical, and psychosocial variables. Descriptive analyses included participants with known TNBC (n=85) or non-TNBC (n=245) disease. Univariable and multivariable analyses were conducted to examine differences in factors associated with HRQOL.ResultsIn unadjusted analyses, TNBC participants had significantly lower FACT-B total scores (90.1±27.9) compared to non-TNBC (98.5±27.6) participants (p&nbsp

Anthracycline-based cardiotoxicity is concerning for women with breast cancer and portends a dose-dependent risk of developing left ventricular dysfunction. Overall, the prevalence of heart failure (HF) is ≈2% of the total US population; however, BRCA-deficient mice have shown increased HF. We evaluated for the inherent risk of HF in women with BRCA mutations to determine whether treatment with anthracycline-based therapy increased this risk. We obtained results on BRCA mutation carriers regarding cancer treatment and HF, identified through the BRCA patient advocacy organization Facing Our Risk for Cancer Empowered (FORCE) and the Moffittbased Inherited Cancer Registry. In our patient group (232 BRCA1 and 159 BRCA2 patients; 10 with both mutations), 7.7% reported HF, with similar proportions in BRCA1 versus BRCA2 carriers (7.4% and 8.2%, respectively). These proportions are significantly higher than published rates (p < 0.001). There was no statistically significant difference in HF rates comparing anthracycline-treated versus anthracycline-naïve patients however (7.1% vs. 8.3%; p = 0.67). In addition, 9.1% of BRCA1 carriers and 8.2% of BRCA2 carriers reported arrhythmias. BRCA mutation carriers showed increased risk of cardiotoxicity versus the general population and an overall increased risk of cardiotoxicity from anthracycline-based therapy. Our study supports data that BRCA carriers have increased noncancer mortality from cardiotoxicity. A prospective trial to determine HF and conduction abnormalities in this population is warranted.

Background Acute myeloid leukemia (AML) is primarily a disease of older adults, with 40-50% of patients ≥ 70 years old at diagnosis. Optimal frontline therapy for elderly AML patients remains controversial. Intensive chemotherapy (IC) is often favored in those AML patients who present with leukocytosis (P-AML), yet the evidence to support this practice as opposed to lower intensity therapy is scarce. We aimed to investigate the outcomes of older patients with P-AML based on treatment choice of intensive chemotherapy (IC) vs hypomethylating agents (HMA). Methods We retrospectively analyzed 983 elderly AML patients (age ≥ 70 years) treated at Moffitt Cancer Center between 1995 and 2016. Patients with prior exposure to HMA for non-AML diagnoses were excluded. We focused on P-AML patients, defined as baseline WBC ≥ 10x109/L, who received initial therapy with either: intensive chemotherapy (IC) (defined as daunorubicin/cytarabine or equivalent) or hypomethylating agents (HMA) (azacitidine (AZA) or decitabine (DEC)). Age, type of AML, history of antecedent hematologic disease, cytogenetics (per European LeukemiaNet (ELN) criteria), Eastern Cooperative Oncology Group (ECOG) performance status, Charlson comorbidity Index (CCI), complete blood counts and myeloblast percentage at time of diagnosis were obtained for each patient. Kaplan-Meier analysis was performed to calculate overall survival (OS) and the log-rank test was used to determine significance where a p-value of 0.05 was defined as significant. Fisher's exact t-test, hazard ratios (HR) and confidence interval (CI) were calculated using GraphPad Prism v7.03. Univariate and multivariate analysis for the baseline characteristics and type of therapy were performed using SPSS v24.0 to determine prognostic impact. Results Within the entire cohort of older AML patients, we identified 156 who were treated with either HMA (n=41) or IC (n=115). Baseline characteristics of these patients are described in Figure 1A. Significant baseline differences in age, hemoglobin, WBC, ELN cytogenetic category, marrow blast %, and CCI score were observed between the HMA and IC groups. Most notably, the HMA group were older (median age 77 yrs vs 74 yrs, p=0.0037), had a higher incidence of poor-risk cytogenetics (36.6% vs 7%), and were more likely to have CCI score ≥ 3 (29.3% vs 8.7%). Median time of initial treatment was 4.3 months (range: 0.10-70.0 months) in the HMA group compared to 0.5 months (range: 0.33-1.90months) in the IC group. Median OS of the entire group was 7.85 mo. Median OS in the HMA-treated patients was superior to IC treated patients (13.7 mo vs. 5.1 mo, HR 0.63, 95% CI 0.443 - 0.886, p=0.0082) (Figure 1B). The 12 month survival rate was 55.0% in the HMA group and 31.0% in the IC group (p=0.0082). Fifty-two (33%) patients achieved CR/CRi. There was no difference in CR/CRi rates between HMA or IC treated cohorts (30.0% vs. 34.8%, p=0.6983). Rate of relapse upon achievement of CR/CRi was not statistically significant between HMA and IC cohort (41.7% vs. 62.5%, p=0.3181). The 30-day mortality rate was lower in the HMA group compared to the IC group (7.3% vs 24.4%, p=0.0217). Univariate analysis identified treatment type (p Conclusions Elderly patients (age ≥ 70) with proliferative AML appear to achieve a survival advantage with HMA-based frontline therapy compared to IC, despite a disproportionately higher incidence of traditionally adverse prognostic features (poor-risk cytogenetics, high CCI score) in the HMA group. The reasons for this observation are unclear, but could relate to a higher early death rate with IC or biologic/molecular features that induce greater sensitivity to HMAs, which should be studied in future analyses. Although this study was limited by small size and retrospective nature, our findings cast doubt on the notion that intensive therapy should be the standard frontline approach in elderly patients proliferative/high WBC AML. Download : Download high-res image (266KB) Download : Download full-size image Disclosures Sallman: Celgene: Research Funding. Padron: Incyte: Honoraria, Research Funding. Komrokji: Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria. Lancet: Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy; Pfizer: Other: Institutional research funding.

Background: Autologous hematopoietic cell transplantation (HCT) followed by maintenance therapy with an immunomodulatory agent or a proteasome inhibitor remains an important strategy for upfront treatment in multiple myeloma (MM) with progression-free survival (PFS) and overall survival (OS) advantage. We designed a two-arm, open-label prospective study to examine the safety and tolerability of two different dosing schedules of an oral pan-histone deacetylase inhibitor, panobinostat (pano) as an alternative maintenance therapy option in patients with MM (NCT02722941). Methods: A total of 30 MM patients who underwent autologous HCT within the preceding 90 to 180 days were enrolled at Moffitt Cancer Center using a sequential alternating allocation to starting dose of either Cohort A: 20 mg PO 3/week, q 2 weeks on a 28-day cycle, or Cohort B: 10 mg PO daily for 7 days, q 2 weeks on a 28-day cycle, for 12 cycles. Dose level -1 was cohort A: 15 mg 3/week; and cohort B: 10 mg 4/week. Patients with clinically significant cardiac diseases, bradycardia, QTc > 470 msec, bifascicular block were ineligible. EKG was performed on pre- and post-dose on day 1 & 5 of cycle 1, and pre-dose on day 1 of cycles 2-4. Relative dose intensity (RDI), a ratio of amount of drug actually delivered in mg over the amount of planned dose in mg, was calculated to evaluate the treatment feasibility as a surrogate measure. Results: The median age of the entire cohort was 60 (range, 40-73) years with a male/female = 18/12. Disease characteristics are summarized in the Table. Patients initiated pano maintenance at a median of 131 (range 91 - 178) days after autologous HCT. As of 8/1/2019, 16 patients (8 in each cohort) completed full 12 cycles of pano. The RDI for the entire cohort, cohort A, and cohort B was 94.1% (33,750mg/35,860, 98% (16,350mg/16,680mg), and 90.7% (17,400mg/19,180mg), respectively. One patient in cohort A had dose reduction, and 6 patients in cohort B had dose reductions with cytopenias (43%) and GI toxicities (43%) being the most common reasons. No patients required dose modifications due to QT prolongation thus far. There were 3 possibly treatment-associated serious adverse events (pneumonia=2; colitis=1) but all patients successfully resumed pano. Three patients progressed while on pano maintenance. No mortality has been observed thus far. Ten patients are still on pano treatment. The median follow-up is 11 (range, 1-29) months. Conclusions: RDI is 90% overall and panobinostat as a single oral maintenance agent either at 20 mg three times per week or 10 mg po daily for 7 days on alternating weeks appears to be overall well tolerated. There were more dose reductions required in the 10 mg starting dose (cohort B). Panobinostat is a safe alternative for maintenance therapy after autologous HCT. Longer follow-up is needed to confirm the utility of this approach and updated results will be presented at the meeting. Disclosures Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Baz:Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shain:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Locke:Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Alsina:Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau. OffLabel Disclosure: Panobinostat single agent maintenance therapy after autologous hematopoietic cell transplantation for multiple myeloma

Background: High-dose melphalan and autologous hematopoietic cell transplantation (HCT) remains a crucial treatment modality for patients with multiple myeloma (MM). Strategies to improve the conditioning regimen have been explored with addition of novel targeted therapies previously with limited success. Selinexor, an orally available selective inhibitor of nuclear export (SINE), targeting Exportin-1 (XPO-1), was recently approved by the Food and Drug Administration (FDA) for relapsed/refractory MM. Our pre-clinical data show synergy between selinexor and bifunctional alkylating agents in several MM models. Therefore, we hypothesized that the addition of selinexor to high-dose melaphalan would be safe and improve outcomes of autologous HCT in MM. Methods: We designed a single institution, standard 3+3 dose escalation phase 1 study to evaluate the combination of selinexor (given at 40 mg po (dose level 1); 60 mg (dose level 2); and 80 mg (dose level 3) on days -3 and -2 before melphalan) and high-dose melphalan (100 mg/m2 IV on days -3 and -2) as a conditioning regimen for autologous HCT in patients with MM achieving either partial response (PR) or very good partial response (VGPR) after less than 4 lines of systemic anti-myeloma chemotherapy (NCT02780609). The primary objective was to establish a maximum tolerated dose (MTD) and identify a recommended phase 2 dose (RP2D). Results: From 08/2017 to 03/2019, a total of 12 MM patients (pts) received autologous HCT under the phase 1 protocol at Moffitt Cancer Center. Baseline characteristics included: a median age of 57 (range, 43-69); M:F = 7:5; IgG subtype=9, light chain type=2, IgD subtype=1; 92% with Durie-Salmon stage 3; 22% with high-risk disease based on del17p/t(4;14) (2/9, n=3 with unknown risk); a median number of induction=1 (range, 1-2); all received bortezomib-based induction, 83% received immunomodulatory agent, 17% received daratumumab. Pre-HCT responses were PR=4; VGPR=8. Pts received a median of 4.16 (range, 2.16-5.73) million CD34+ cells/kg. Neutrophil engraftment occurred with a median of 11 (range 11-12) days, and a platelet engraftment with a median of 15 (range, 10-36) days. Three pts each entered in dose level 1 and 2; and 6 pts at dose level 3. One pt in dose level 2 did not receive dexamethasone on day -1 due to grade (G) 3 hyperglycemia. One pt in dose level 3 (80 mg selinexor) did not receive day -2 dose of selinexor due to liver function test (LFT) abnormality (ALT > 2x ULN) which was considered as dose-limiting toxicity (DLT) as second dose of selinexor was not given. LFTs normalized after HCT. Dose level 3 was expanded to 3 additional pts and no additional DLTs were observed. Treatment-related serious adverse events (SAEs) included: G3 febrile neutropenia=3, G3 diarrhea=1, G3 nausea=1, G3 small bowel obstruction=1, G3 acute kidney injury=1, G3 lung infection=1. Post-HCT responses at day +90 were complete response (CR)=2, VGPR=6, PR=3, and progression=1. CR conversion rate was 16.7% though phase 1 portion of the study was not powered to evaluate the CR rate. Therefore, RP2D was established as selinexor 80 mg on days -3 and -2. The study is proceeding to the phase 2 portion to assess the efficacy of this combination. Conclusions: The combination with selinexor 80 mg po with high-dose melphalan at 100 mg/m2 on days -3 and -2 (dose level 3) was well tolerated and engraftment kinetics were not altered. A phase 2 study of selinexor 80 mg with high-dose melphalan and autologous HCT is ongoing (NCT02780609). Disclosures Nishihori: Karyopharm: Research Funding; Novartis: Research Funding. Alsina:Amgen: Speakers Bureau; Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau. Baz:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; Merck: Research Funding; Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding. Shain:Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy; AbbVie: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Sullivan:Karyopharm: Research Funding. OffLabel Disclosure: Selinexor in combination with high-dose melphalan

Introduction: Higher infused total nucleated cell dose (TNC) in allogeneic bone marrow transplant (BMT) with post-transplant cyclophosphamide (PTCy) resulted in improved overall survival (OS) in a recent report (McCurdy, et al. BBMT. 2018). As many centers prefer peripheral blood stem cell grafts (PBSCT) with PTCy, the optimal cell dose with this platform requires elucidation. Methods: We retrospectively evaluated 144 consecutive adult patients with hematologic malignancies treated at the Moffitt Cancer Center between 2012-2018 with allogeneic T-cell replete PBSCT followed by PTCy-based graft-versus-host disease (GVHD) prophylaxis. Data were extracted from the Moffitt BMT Research & Analysis Information Network (BRAIN) database. Both myeloablative (n=87) and reduced intensity (n=57) conditioning regimens were included. For analyses, CD34+ cell dose was stratified into low (10x106/kg). TNC was stratified as higher or lower than the median. CD3+ T cell dose was evaluated as a continuous, linear variable. Associations with transplant related survival outcomes were assessed using univariate and multivariate Cox proportional hazard survival models. Fine and Gray regression models were used to assess associations of transplant related endpoints with competing risks. Kaplan Meier curves and cumulative incidence function curves were also plotted. RESULTS: The median follow-up for the entire cohort was 24 months. The median age at PBSCT was 58 (range: 21-76) years. Donors were haploidentical (n=72, 50%), matched unrelated (n=39, 27%), matched related (n=18, 13%), and mismatched unrelated (n=15, 10%). Median CD34+ cell dose was 8.12 x 106/kg (range: 2.27 - 22.4 x 106/kg). Stratified CD34+ dose was low for 16 patients (11.1%), intermediate for 93 patients (64.6%), and high for 35 patients (24.3%). Median CD3+ dose was 2.89 x 108 (range: 2.33 x 105 - 6.54 x 108/kg). Median TNC was 9.66 x 108/kg (range: 3.82 x 108 - 1.04 x 109/kg). Overall, successful neutrophil engraftment by day 30 was achieved in 94% (95% CI 91-98%) and platelet engraftment (>20,000/mL) by day 100 in 87% (95% CI 81-93%) of all patients. The likelihood of neutrophil recovery was similar in the high and low CD34+ cell groups, while it was higher for the intermediate CD34+ cell group (HR=1.52, 95% CI 1.0-2.2; p=0.03). Platelet recovery was similar in the intermediate and high CD34+ cell groups, but significantly lower in low CD34+ cell group (HR=0.38, 95% CI 0.2-0.8; p=0.01). CuI of grade II-IV acute GVHD at day 100 was 39% (95% CI 32-48%) and of grade III-IV acute GVHD was 10% (95% CI 6-17%). CuI of chronic GVHD at 2 years was 50% (95% CI 41-59%). The CD34+ cell dose had no significant impact on either acute or chronic GVHD. Nonrelapse mortality (NRM) at 1 year was 19% (95% CI 13-27%). By CD34+ cell dose, the rates of NRM for low, intermediate, and high dose were 46% (95% CI 25-85%), 15% (95% CI 10-25%), and 15% (95% CI 7-34%), respectively (p=0.002). Relapse rate was 30% at 2 years with no differences across dose levels. Progression free survival (PFS) probability at 2 years was 47% (95% CI 39-57%) for the entire group, 0% (95% CI 0%) for the CD34+ low group, 53% (95% CI 42-65%) for the intermediate group and 51% (95% CI 35-73%) for the high dose group (p=0.0003). Two-year OS for the entire group was 57% (95% CI 49-67%), and was inferior in the low group (0%, 95% CI 0%) with no difference between the intermediate (61%, 95% CI 50-73%) and high (67%, 95% CI 52-87%) CD34+ cell dose groups (p=0.0002). In multivariable modeling, the low CD34+ cell dose group was associated with worse NRM (HR=4.1, 95% CI 1.2-14.5, p=0.03), PFS (HR=2.9, 95% CI 1.3-6.5, p=0.01), and OS (HR=3.2, 95% CI 1.4-7.6, p=0.01) compared with the high group, while there were no differences between the high and intermediate groups. Increasing CD3+ dose was also associated with improved NRM (HR=0.8, 95% CI 0.69-0.97, p=0.02), PFS (HR=0.7, 95% CI 0.5-0.9, p=0.02), and OS (HR=0.7, 95% CI 0.5-0.9, p=0.004). TNC had no impact on survival outcomes. CONCLUSION: In patients receiving allogeneic PBSCT with PTCy, CD34+ cell doses below 5 x 106 cells/kg yielded inferior OS and PFS, attributable to higher NRM. Doses of 5-10 x 106 cells/kg and >10 x 106 cells/kg resulted in comparable outcomes. Higher CD3+ dose/kg was also associated with improved survival outcomes. Overall, this study supports targeting a CD34+ dose of >5 x 106 cells/kg for allogeneic PBSCT with PTCy. Disclosures Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Bejanyan:Kiadis Pharma: Other: advisory board.

European LeukemiaNet (ELN) 2017 updated prognostic system for acute myeloid leukemia (AML), which incorporates both cytogenetic and molecular risks, stratifying patients into 3 distinct genetic risk groups: favorable, intermediate and adverse. While most patients in favorable risk group can be cured with chemotherapy alone, the majority of patients in intermediate and adverse genetic risk groups are considered for curative allogeneic hematopoietic stem cell transplantation (alloHCT). However, the impact of ELN 2017 risk classification on survival of AML patients after alloHCT remains unclear. We examined the prognostic significance of ELN 2017 classification on 503 AML patients in first or second complete remission (373 CR1/ 130 CR2) receiving alloHCT at Moffitt Cancer Center) from 2005-2016. Patients were classified into favorable (n=58, 11.6%), intermediate (n=284, 56.8%) and adverse (n=158, 31.6%) ELN risk groups. The median age at alloHCT for the entire cohort was 55 years (range, 18-76 years) and 29% of all patients had many comorbidities (HCT ≥3) at transplant. Disease risk index (DRI) was low in 38 (7.6%), intermediate in 393 (78.6%) and high in 69 (13.8%) patients, and 22% (n=109) of all patients had secondary AML. Myeloablative conditioning was used in 77% (n=389) of patients, while 23% (n=114) received reduced-intensity conditioning regimen. HLA-matched unrelated donor (47%) was the most commonly used donor type, followed by matched related (27.7%) and mismatched donors (n=75, 9.8%). For the entire cohort, 2-year overall survival (OS) was 56% (52-60%) and leukemia-free survival (LFS) was 51% (47-55%). Patients with CR1 and CR2 status at alloHCT had similar OS (58% vs. 53%, p=0.17). We identified that ELN 2017 genetic risk is prognostic of OS after alloHCT in patients with AML: 72% (61-84%) in favorable risk vs. 60% (54-66%) in intermediate risk vs. 45% (38-53%) in adverse risk groups (p Our findings highlight the prognostic impact of ELN 2017 genetic risk on survival of AML patients undergoing alloHCT in CR1/CR2. Patients in the adverse risk group had higher risk of relapse and worse survival. Thus, ELN 2017 prognostic system can help identify AML patients in CR1/CR2 who can benefit from clinical trials offering relapse reduction strategies in order to improve their survival.

BACKGROUND: Excision repair cross complementing 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) are molecular determinants that predict sensitivity or resistance to platinum agents and gemcitabine, respectively. Tailored therapy using these molecular determinants suggested patient benefit in a previously reported phase 2 trial. Here, we report an individual patient analysis of prospectively accrued patients who were treated with the “personalized therapy” approach versus other “standard,” noncustomized approaches. METHODS: Patients who had nonsmall cell lung cancer (NSCLC) with extranodal metastatic disease and an Eastern Cooperative Oncology Group performance status of 0/1 were accrued to 4 phase 2 clinical trials conducted at the H. Lee Moffitt Cancer Center: Trial A (first-line carboplatin/gemcitabine followed by docetaxel), Trial B (docetaxel and gefitinib in patients aged ≥70 years), Trial C (combination therapy with carboplatin/paclitaxel/atrasentan), and Trial D (personalized therapy based on ERCC1 and RRM1 expression). Patients with low RRM1/low ERCC1 expression received gemcitabine/carboplatin, patients with low RRM1/high ERCC1 expression received gemcitabine/docetaxel, patients with high RRM1/low ERCC1 expression received docetaxel/carboplatin, and patients with high RRM1/high ERCC1 expression received vinorelbine/docetaxel. Patients who were treated on Trials A, B, and C were pooled together and analyzed as the “standard therapy” group. Patients accrued to Trial D were called the “personalized therapy” group. Individual patient data were updated as of February 8, 2011. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS: There were statistically significant improvements between the personalized therapy group versus the standard therapy group in response (44% vs 22%; P = .002), OS (median: 13.3 months vs 8.9 months; P = .016), and PFS (median: 7.0 months vs 4.3 months; P = .03). CONCLUSIONS: The results from individual patient analyses suggest that ERCC1 and RRM1/tailored selection of first-line therapy improved survival over standard treatment-selection approaches. Cancer 2012. © 2011 American Cancer Society.

National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer treatment and surveillance are well established, but similar guidelines on male breast cancers are less recognized. As an NCCN institution, our objective was to examine practice patterns and follow-up for male breast cancer compared to established guidelines for female patients. After Institutional Review Board approval, a prospective breast database from 1990 to 2009 was queried for male patients. Medical records were examined for clinico-pathological factors and follow-up. The 5-year survival rates with 95% confidence intervals were estimated using Kaplan-Meier method and Greenwood formula. Of the 19,084 patients in the database, 73 (0.4%) were male patients; 62 had complete data. One patient had bilateral synchronous breast cancer. The median age was 68.8 years (range 29-85 years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0-10.0 cm). All cases had mastectomy (29 with axillary node dissection, 23 with sentinel lymph node biopsy only, 11 with sentinel node biopsy followed by completion axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in 34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received post-mastectomy radiation. Median follow-up was 26.2 months (range: 1.6-230.9 months). The 5-year survival estimates for node positive and negative diseases were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast cancer, treatment options based on current female breast tumors produce comparable results to female breast cancer. Increased awareness and a national registry for patients could help improve outcomes and tailor treatment recommendations to the male variant.

Background and Objectives To improve the likelihood of achieving a margin-free resection, neoadjuvant induction chemotherapy with GTX (gemcitabine, docetaxel, and capecitabine) followed by 5-FU-IMRT was administered to patients with borderline resectable pancreatic cancer. The utility of computed tomography (CT), endoscopic ultrasound (EUS), positron emission tomography (PET), and CA 19-9 during diagnostic workup and assessment of response was also examined. Methods Seventeen patients with borderline resectable pancreatic cancer received a median of three cycles of neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT with dose painting. CA 19-9, CT mass size, and PET SUV were examined before and after neoadjuvant treatment. Results Diagnostic EUS and CT scans displayed similar mean mass sizes and extent of vascular involvement. Eight of the 17 patients achieved an R0 resection. Median CA 19-9 levels, CT mass size, and PET SUV all significantly decreased after neoadjuvant therapy. The median progression-free survival and overall survival were 10.48 and 15.64 months, respectively. Six patients are still alive. Conclusions Neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT shows promise in improving the likelihood of resectability with negative margins in borderline resectable pancreatic cancer. CT and EUS play complimentary roles during diagnostic workup. CT scans, CA 19-9, and PET scans are useful in judging response to neoadjuvant therapy. J. Surg. Oncol. 2011;104:155–161. © 2011 Wiley-Liss, Inc.

Disordered glucose metabolism is a common complication of glucocorticoid therapy for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT). We aimed to examine the impact of dysglycemia on outcomes in 173 recipients of HCT treated with glucocorticoids for aGVHD. A total of 147 of these patients contributed data to a landmark analysis performed at 12 weeks post-HCT. Median aGVHD onset was 21 days (range: 5–79) after transplant. Median duration of glucocorticoid therapy was 381 days (range: 15–1632). Glucose values were obtained from glucocorticoid initiation date to death or last follow-up, resulting in 11,588 total values. The median (range) for each parameter were: maximum 292 mg/dL (128–694), minimum 75 mg/dL (34–142), average 142 mg/dL (86–327), and standard deviation 46 mg/dL (12–108). Baseline diabetes mellitus predicted significantly greater maximum, mean, and standard deviation. With median follow-up of 20 months (range: 3–55), median overall survival (OS) was 33.7 months (95% confidence interval [CI] 16.4—not reached). On multivariable analysis, maximum, average, or standard deviation of glucose values predicted OS and maximum or average glucose values predicted nonrelapse mortality (NRM). Minimum glucose values of (0–60 mg/dL) were associated with worsened OS and increased NRM. Those patients treated with insulin or oral agents suffered significantly worse OS and increased NRM compared to patients who did not need therapy. Finally, those with sustained maximum values >200 mg/dL despite treatment suffered worse OS and increased NRM. These data suggest an independent adverse effect of dysglycemia in patients treated with glucocorticoids for aGVHD, and argue for stringent glycemic control in this setting.

We examined pharmacokinetic-targeted IV busulfan (75-170 mg/m(2), with target AUC of 3500-6000 μmol min) and fludarabine (40 mg/m(2)) × 4 days with rituximab (t-IV Bu/Flu + rituximab) 375 mg/m(2) on days +1 and +8 followed by allogeneic hematopoietic cell transplantation in 19 patients (median age 56, range 35-68 years) with CD20+ lymphoid malignancies. Median time to neutrophil and platelet engraftment was 15 and 12 days. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 58% (95% confidence interval, CI 39-85%), and chronic GVHD was 50% (95% CI 28-88%). With a median follow up of 7 (range 1-31) months, overall response was observed in 15, and stable or progressive disease in 4. Overall survival at 1 year was 67%. Engraftment, chimerism, and infectious complications did not differ significantly from a contemporaneous non-rituximab containing comparator group. The addition of rituximab 375 mg/m(2) to t-IV Bu/Flu does not appear to adversely affect engraftment, donor chimerism, or increase the risk of infectious complications.

Allogeneic hematopoietic cell transplantation (HCT) remains the only curative approach for patients with myelofibrosis [1,2]; however, it can result in substantial transplant related mortality. We retrospectively examined the outcomes of 18 myelofibrosis patients who underwent allogeneic HCT between 2000 and 2008. Eleven (61%) had high-risk prognostic scores. Fourteen (78%) received a reduced-toxicity regimen of pharmacokinetically-targeted (a median AUC of 5,300 μm min ―1 ; range, 3,500-6,000) intravenous busulfan plus fludarabine (t-IV Bu/Flu). Source of hematopoietic cells were from HLA matched-related (50%), matched-unrelated (44%), or mismatched-unrelated (6%) donors. Fourteen (78%) received G-CSF-mobilized peripheral blood stem cells. Median time to neutrophil and platelet engraftment were 17 (range, 15-28) and 18 (range, 8-213) days, respectively. There were two cases of secondary graft failure after myeloablative conditioning and one case following t-IV Bu/Flu. Overall survival was 50.2% at 54 months (95% confidence interval [C: 24.1-71.6%) with a median follow-up of 15 (range, 3-63) months. Nonrelapsed mortality (NRM) at 100 days and at 1-year were 0 and 22.6% (95% CI: 9.1-49.7%), respectively. The causes of NRM comprised of infections (56%) and graft-versus-host-disease (44%). t-IV Bu/Flu is a feasible conditioning regimen for allogeneic HCT in myelofibrosis showing encouraging engraftment with 7% graft failure rate.

TPS525 Background: The current standard of treatment for cholangiocarcinoma (CCA) is gemcitabine and cisplatin that favored both overall survival (OS) and progression free survival (PFS) when compared to gemcitabine alone. The survival however remains less than than 1 year. Predominant activation of PI3K/AKT signaling pathway is seen in cell line and human tumors of CCA promoting tumorigenesis and increased resistance to radiation and chemotherapy. Inhibition of this pathway sensitizes CCA cells to therapies. Copanlisib is a selective and reversible pan-class I PI3K inhibitor. In preclinical studies, copanlisib demonstrated anti-tumor activity in PIK3CA mutated cells particularly in BC. In a Phase I study, 4 treatment naïve patients with CCA showed response, including 1 complete response. The maximum tolerated dose of copanlisib was determined to be 0.8 mg/kg in this study. We hypothesize that the addition of copanlisib to gemcitabine + cisplatin will enhance the efficacy of the current standard regimen in advanced CCA. Tumor tissue will be collected on every patient for PTEN immunohistochemical staining and NGS analysis using a 26-genes panel. Methods: This is a single institution phase II single arm two-stage design trial using copanlisib in combination with gemcitabine and cisplatin in patients with advanced CCA. Eligible patients include those diagnosed with advanced, unresectable CCA that are treatment naïve or should have received adjuvant treatment more than 6 months prior to initiating the trial. Patients will be treated with Cisplatin (25 mg/m2) plus Gemcitabine (1000 mg/m2) and Copanlisib (60 mg) on days 1 and 8 on a 21 days cycle. Primary objective of the study is PFS at 6 months with secondary objectives being response rate, median PFS, OS, safety and tolerability. Accrual began on June 28, 2016, with planned enrollment for 25 patients. 14 eligible patients will be enrolled in the first stage. If 8 or more patients (≥57%) are alive and progression free at 6 months, an additional 11 patients will be enrolled in the second stage. 11 patients have been enrolled until now. After 3 cycles, response and progression will be evaluated using RECIST v1.1. Clinical trial information: NCT02631590.

Acute graft vs host disease (aGVHD) is a significant obstacle to successful allogeneic hematopoietic cell transplantation, as only 30-40% of those with aGVHD show complete response to front-line glucocorticoids. The role of mycophenolate mofetil (MMF) as salvage therapy in steroid-refractory aGVHD remains incompletely defined. Here, we examine outcomes of 27 patients with refractory aGVHD treated with MMF as second-line therapy. Seven (26%) patients achieved complete remission (CR) of steroid-refractory aGVHD with only the addition of MMF as salvage therapy. CR of aGVHD differed by overall grade at salvage (grade I, 1/3; grade II, 5/12; grade III 0/5; grade IV, 1/7) with odds ratio for CR in grade I/II vs III/IV of 7.3 (95% CI: 0.7-72.6, P=0.09). Overall survival (OS) at 3 years was 40%. Overall aGVHD grade at salvage (hazard ratio (HR) grade I/II vs III/IV 0.18 (95% CI: 0.06-0.57), P=0.003) and achievement of CR (HR 0.12 (95% CI: 0.04-0.39), P=0.0004) were significant predictors of OS. MMF was overall well tolerated, with only two patients requiring discontinuation for myelosuppression. MMF shows activity in the salvage of steroid-refractory, grades I-II aGVHD.

Glucocorticoids have gone unchallenged as an essential component of primary therapy for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) despite limited complete response rates and adverse effects from this therapy. The role for alternate immunosuppressive agents as primary aGHVD treatment remains unexamined. In a series of 10 patients at high risk for corticosteroid toxicity or leukemia relapse who developed biopsy-proven grade II-III aGVHD after hematopoietic cell transplantation, we report that primary therapy with sirolimus resulted in durable complete remission of aGVHD in 5 (50%) without requirement for glucocorticoids. Mild chronic GVHD (cGVHD) developed in 4 (40%). Projected overall survival (OS) at 18 months is 79% (95% confidence interval [CI]: 38.1%-94.3%), and projected relapse-free survival (RFS) at 15 months is 70% (95% CI: 32.9%-89.2%). Sirolimus was well tolerated with mild and reversible thrombotic microangiopathy occurring in 2 patients. This experience provides preliminary evidence for the efficacy of sirolimus as a sole primary therapy in the treatment of aGVHD.

BackgroundIn this study we retrospectively evaluated the capability of computed tomography (CT)-based radiomic features to predict epidermal growth factor receptor (EGFR) mutation status in surgically-resected peripheral lung adenocarcinomas in an Asian cohort of patients.Patients and MethodsTwo hundred ninety-eight patients with surgically resected peripheral lung adenocarcinomas were investigated in this institutional review board-approved retrospective study with requirement waived to obtain informed consent. Two hundred nineteen quantitative 3-D features were extracted from segmented volumes of each tumor, and 59 of these, which were considered independent features, were included in the analysis. Clinical and pathological information was obtained from the institutional database.ResultsMutant EGFR was significantly associated with female sex (P = .0005); never smoker status (P < .0001), lepidic predominant adenocarcinomas (P = .017), and low or intermediate pathologic grade (P = .0002). Statistically significant differences were found in 11 radiomic features between EGFR mutant and wild type groups in univariate analysis. Mutant EGFR status could be predicted by a set of 5 radiomic features that fell into 3 broad groups: CT attenuation energy, tumor main direction, and texture defined according to wavelets and Laws (area under the curve [AUC], 0.647). A multiple logistic regression model showed that adding radiomic features to a clinical model resulted in a significant improvement of predicting power, because the AUC increased from 0.667 to 0.709 (P < .0001).ConclusionComputed tomography-based radiomic features of peripheral lung adenocarcinomas can capture useful information regarding tumor phenotype, and the model we built can be useful to predict the presence of EGFR mutations in peripheral lung adenocarcinoma in Asian patients when mutational profiling is not available or possible.

e21530 Background: In geriatric assessments, comorbidity is often assessed with tools such as the Charlson comorbidity index (CCI) and the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). In studies of older patients with colorectal cancer (CRC), comorbidity was mainly measured using the CCI, and inconsistent results about the correlation comorbidity with overall survival (OS) were found. In order to refine our understanding of the impact of comorbidity, we evaluated its correlation with OS using the CIRS-G and heat maps to elicit the subgroups with the highest impact. Methods: We retrospectively reviewed 153 consecutive patients from the Total Cancer Care database, aged ≥65 with stage 4 CRC, who underwent chemotherapy at Moffitt Cancer Center from 2000 to 2015. The association between CIRS-G scores and OS was examined by the Cox proportional hazards regression model. Results: Median age at diagnosis was 71 years. Forty-eight % of patients had an ECOG PS of 0. Median MAX2 score of chemotherapies was 0.119. Median total score of CIRS-G was 8 (1-20) and median severity index was 0.57 (0.07-1.43). The most common comorbidities were vascular, EENT and larynx, and respiratory diseases. Eleven patients had 1 comorbidity and 1 patient had 2 comorbidities at level 4 severity. Median OS of all patients was 25.1 months (95% CI 21.2-27.6). In univariate analysis, the number of CIRS-G level 4 comorbidities was a significant worse prognostic factor for OS (0 vs 1 or 2, HR 2.16, p = 0.017). In multivariate analysis, ECOG PS ≥2, poorly differentiated histology, age at diagnosis and numbers of CIRS-G level 4 comorbidities were significant worse prognostic factors for OS. ECOG PS ≥2 and age at diagnosis were significant worse prognostic factors for unplanned hospitalization. Conclusions: The OS in the elderly metastatic CRC patients was good and similar to the general population with this disease. The number of CIRS-G level 4 comorbidities was associated with worse OS but no specific CIRS-G category was individually associated with OS.

Purpose: Black women are more likely to develop early onset (age ≤50 years) breast cancer and have the lowest five year cause specific survival rate of any U.S. racial or ethnic group. The disparity in incidence and survival can be attributed partially to the higher rate of triple negative breast cancer (TNBC) in Blacks. Yet, little is known about health-related quality of life (HRQOL) among Black women with TNBC. Guided by the Contextual Model of HRQOL, the purpose of these analyses is to examine factors associated with HRQOL in patients with TNBC and non-TNBC. Methods: Black women with invasive breast cancer at age ≤50 years and diagnosed between 2009-2012 were recruited through the Florida State Cancer Registry as part of a population-based case-only study to investigate etiology and outcomes of early-onset invasive breast cancer (n=456). A subset of participants (n=355) consented to complete additional study questions assessing those sociodemographic, clinical, and psychosocial variables selected based on the Contextual Model. The Functional Assessment of Cancer Treatment-Breast (FACT-G) was used to assess HRQOL. Descriptive analyses included those participants confirmed to have either TN or non-TN disease (n=330); univariable and multivariable analyses included participants who met the aforementioned criteria and completed baseline HRQOL data (n=299). Results: Participants in the TNBC and non-TNBC group were similar (p>0.05) with respect to age (TNBC: 41.4 ±5.9 years; non-TNBC: 42.2 ±6.5) and time since diagnosis (TNBC: 18.5 ±7.0 months; non-TNBC: 19.8±10.1). TNBC participants had lower mean FACT-G total scores (71 ± 22.3) compared to non-TNBC (77 ± 21.6) participants (p Conclusions: The Contextual Model of HRQOL provides a useful framework for evaluating HRQOL in Black breast cancer patients; differences based on triple negative disease status suggest possible intervention targets to improve HRQOL in these women. Effective interventions should focus on reducing anxiety at the individual level, with additional consideration for depressed affect, cancer worry, and social support in the non-TNBC group. For patients with TNBC, interventions may include addressing fatalistic cognitions and collectivist attitudes that may adversely affect HRQOL. Citation Format: Susan T. Vadaparampil, Juliette Christie, Kristine Donovan, Jongphil Kim, Bianca Augusto, Cheryl Holt, Kimlin Ashing, Chanita Hughes Halbert, Tuya Pal. Health-related quality of life in black breast cancer patients with Triple Negative Breast Cancer (TNBC). [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B26.

We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (MM). The primary objective of the phase 1 was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate. Patients received 6-8 cycles of CVDD at four dose levels. There were no dose-limiting toxicities. The MPD was cyclophosphamide 750 mg/m(2) IV on day 1, bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, 11, pegylated liposomal doxorubicin 30 mg/m(2) IV on day 4, and dexamethasone 20 mg orally on the day of and after bortezomib (21-d cycle). Forty-nine patients were treated at the MPD of which 22% had high-risk myeloma. The most common grade ≥3 toxicities included myelosuppression, infection, and fatigue. Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively. After a median follow-up of 34 months, the median progression-free survival was 31.3 months. The 2-yr overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively. CVDD regimen was well tolerated and was highly active in newly diagnosed MM.

Background Mortality associated with allogeneic hematopoietic cell transplantation (allo-HCT) has limited its broader application in patients with non-Hodgkin lymphoma (NHL). Pharmacokinetic treatment with targeted intravenous busulfan combined with fludarabine (BuFlu) was developed as a preparative regimen for acute leukemia and myelodysplasia. Data from this regimen in lymphoid malignancies are limited. Patients and Methods We assessed outcomes in 60 consecutive patients with various subtypes of NHL and a median age of 54 years (range, 27-68 years) who received allo-HCT with targeted intravenous BuFlu between December 2004 and August 2010. The median number of previous therapies was 3 (range, 1-8) and median time from diagnosis to HCT was 32 months (range, 4.5-177.5 months). Results At conditioning, 28 (47%) patients had a complete response (CR). Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus plus methotrexate in 65% of cases. Donors were matched/related (n = 32 [53%]), matched/unrelated (n = 21 [35%]), or mismatched/unrelated (n = 7 [12%]). All patients underwent grafting. The cumulative incidence of grade II/IV acute GVHD was 74% (grade III/IV was 20%). The 2-year cumulative incidence of moderate to severe chronic GVHD was 62%. Nonrelapse mortality (NRM) at 100 days and 3 years was 10% and 25%, respectively. The cumulative incidence of relapse was 27%. Three-year progression-free and overall survival for all patients was 47.8% and 55%, respectively. Conclusion Targeted intravenous BuFlu is a relatively well tolerated regimen and offers an alternative option when myeloablation is deemed necessary in patients with NHL.