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Abstract Background Hot flashes (HFs) negatively affect quality of life among perimenopausal and postmenopausal women. This study investigated the efficacy of oxybutynin vs placebo in decreasing HFs. Methods In this randomized, multicenter, double-blind study, women with and without breast cancer with 28 or more HFs per week, lasting longer than 30 days, who were not candidates for estrogen-based therapy, were assigned to oral oxybutynin (2.5 mg twice a day or 5 mg twice a day) or placebo for 6 weeks. The primary endpoint was the intrapatient change from baseline in weekly HF score between each oxybutynin dose and placebo using a repeated-measures mixed model. Secondary endpoints included changes in weekly HF frequency, HF-related daily interference scale questionnaires, and self-reported symptoms. Results We enrolled 150 women. Baseline characteristics were well balanced. Mean (SD) age was 57 (8.2) years. Two-thirds (65%) were taking tamoxifen or an aromatase inhibitor. Patients on both oxybutynin doses reported greater reductions in the weekly HF score (5 mg twice a day: −16.9 [SD 15.6], 2.5 mg twice a day: −10.6 [SD 7.7]), placebo −5.7 (SD 10.2); P < .005 for both oxybutynin doses vs placebo), HF frequency (5 mg twice a day: −7.5 [SD 6.6], 2.5 mg twice a day: −4.8 [SD 3.2], placebo: −2.6 [SD 4.3]; P < .003 for both oxybutynin doses vs placebo), and improvement in most HF-related daily interference scale measures and in overall quality of life. Patients on both oxybutynin arms reported more side effects than patients on placebo, particularly dry mouth, difficulty urinating, and abdominal pain. Most side effects were grade 1 or 2. There were no differences in study discontinuation because of adverse effects. Conclusion Oxybutynin is an effective and relatively well-tolerated treatment option for women with HFs.

Abstract Introduction: Outcome disparities related to race and area-based socioeconomic status (SES) following allogeneic hematopoietic stem cell transplantation (allo-HCT) have been identified in adult patients [Baker et al. 2009]. The relationship between SES and outcomes in pediatric allo-HCT has not been previously described. Among a large cohort of pediatric allo-HCT recipients we sought to determine the impact of area-based poverty on 5-year outcomes of overall survival (OS), acute and chronic graft-versus-host-disease (aGVHD, cGVHD); as well as the short-term outcome of infection through day 100 . Methods: We utilized the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the association of sociodemographic variables with outcomes in two cohorts of pediatric transplant recipients aged <=18 years who received allo-HCT at U.S. centers between 2006-2015. Cohort 1 (malignant) included 2053 children who received myeloablative conditioning for any malignancy. Cohort 2 (non-malignant) included 1696 children who received myeloablative or reduced-intensity conditioning for any non-malignant disease. Zip codes of child's residence were categorized as high-poverty area (>=20% households living below 100% federal poverty level (FPL)) versus low-poverty area (<20% households below 100% FPL) by linkage to U.S. Census data [Krieger et al. 2002]. Individual-level sociodemographic variables including insurance (Medicaid-only vs Other), race (Caucasian vs Black vs Other) and ethnicity (non-Hispanic vs Hispanic) were included as covariates. Cox regression was used to examine the effect of patient-related (age, performance status, insurance, race, and ethnicity), disease-related (disease type and status), and HCT-related (donor/graft type, CMV status, stem cell source, HLA match, donor age and gender, conditioning regimen and intensity, GVHD prophylaxis, year of HCT) variables on the outcomes of interest between the two area-based poverty groups. Results: Fifteen percent (N=299) of children in Cohort 1 lived in a high-poverty area; 35% (N=711) were insured by Medicaid-only; 11% (N=227) were African-American and 20% (N=417) Hispanic. Median follow-up of survivors was 74 months. In multivariable analysis, there was no association between area-based poverty and OS; however, OS was inferior in children with Medicaid-only insurance compared to those with private insurance (HR 1.22 (95% CI 1.06-1.40), p=0.0037) and in Black children compared to Caucasian (HR 2.02 (95% CI 1.10-3.73), p=0.0234). For the secondary outcomes of aGVHD, cGVHD or infection through day 100, there were no associations between area-based poverty, insurance, race, or ethnicity in multivariable analysis. To further explore the independent association of insurance with OS, we performed an ad hoc univariate analysis that demonstrated that insurance-related differences in OS for malignant disease appear to be driven by differences in treatment-related mortality (TRM) (5-year TRM: Medicaid-only 25% (95% CI 22-28) versus 18% (95% CI 16-21) other). Thirteen percent (N=228) of children in Cohort 2 lived in a high-poverty zip code; 35% were insured by Medicaid-only (N=597); 20% (N=332) were African-American and 20% (N=344) Hispanic. Median follow-up of survivors was 74 months. In multivariable analyses, there was no association between area-based poverty, insurance, race or ethnicity and any outcome. Conclusion: Area-based poverty is not associated with disparate outcomes in pediatric allo-HCT for malignant or non-malignant disease. In the setting of malignant disease, insurance-a household-level measure of socioeconomic status-and Black race are independently associated with inferior OS. These results suggest that future prospective investigation of more refined measures of household-level socioeconomic status may identify risk-factors for treatment-related mortality in this population. Disclosures No relevant conflicts of interest to declare.

Abstract Background: The combination of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone is the current standard induction therapy for myeloma. Daratumumab, a monoclonal antibody directed against CD38, is highly effective in treating myeloma and improves response rates and progression free survival (PFS) when added to PI or IMiD. Ixazomib, lenalidomide and dexamethasone (IRd) is an effective, all oral, induction regimen that has been studied in phase 2 and 3 trials. We designed this trial to examine the feasibility and efficacy of adding daratumumab to the IRd regimen. Patients and Methods: Patients with previously untreated MM, with measurable disease and adequate organ function were enrolled irrespective of their transplant eligibility. The primary objective was to determine the rate of complete response to the IRD-Dara combination in patients with NDMM. Treatment consisted of Ixazomib 4mg days 1, 8, 15; lenalidomide 25 mg days 1-21, dexamethasone 40 mg, weekly and daratumumab 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and then every 4 weeks after that. Overall, 40 patients were accrued; data on 38 patients were available for analysis as of July 02, 2018 (Table 1). Results: The median age was 62 (41-81); 52.6% female. All patients were alive and progression free at last assessment with a median follow up of 5.2 (2.0-12.9) months (median 5 cycles, range 2-13). One patient had gone off for alternate therapy. Responses were rapid with 90% partial response or better (32% VGPR) after 2 cycles, and 100% PR or better (50% VGPR) for 32 patients who have completed 4 cycles. The overall best confirmed response rate among the 38 patients was 95% including 11% CR and 47% VGPR. Overall, 231 cycles have been administered across the study, with dose modifications/ hold required for ixazomib, lenalidomide, daratumumab and dexamethasone in 3 (8%), 11 (29%), 2 (5%), and 8 (21%) patients respectively, the most common reasons being hematologic and skin rash. A grade 3 or higher adverse event at least possibly attributed to the study drugs was seen in 42% of patients, hematologic in 37% and non-hematologic in 11% (Figure). 11 patients have so far proceeded to stem cell collection, all have collected adequate numbers of stem cells for one or two intended transplants(median CD34+ collected 8.4 million/kg; range 3.8-12.3). Updated results with additional 6 months of follow up and MRD testing will be presented at the meeting. Conclusion: This represents the first reported results of this combination for treatment of newly diagnosed myeloma. The early results from the use of IRd-Dara in newly diagnosed myeloma suggests excellent efficacy with rapid responses that deepen quickly over the initial cycles of therapy. The regimen was well tolerated with limited dose modifications and no discontinuation for toxicity and no influence on the ability to collect stem cells. Figure. Figure. Disclosures Kumar: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding. Lacy:Celgene: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Gertz:Prothena: Honoraria; Amgen: Consultancy; Abbvie: Consultancy; Teva: Consultancy; annexon: Consultancy; janssen: Consultancy; celgene: Consultancy; Alnylam: Honoraria; Medscape: Consultancy; Apellis: Consultancy; spectrum: Consultancy, Honoraria; Physicians Education Resource: Consultancy; Ionis: Honoraria; Research to Practice: Consultancy.

Abstract Background: Obesity is a prevalent health problem and significant heterogeneity is seen in the body weight and BMI among adult patients undergoing autologous stem cell transplantation (SCT). At least two critical steps of the SCT are influenced by the body weight. Stem cell collection targets are usually determined based on the actual body weight and conditioning chemotherapy doses are usually determined based on corrected ideal body weight. One could hypothesize that since the stem cells home to bone marrow, the ideal body weight (IBW) being based on the height may be a better indicator of the stem cell numbers required rather than the actual body weight (ABW). Since chemotherapy doses are calculated based on corrected ideal body weight, and the volume of distribution is higher in obese patients, these patients may have decreased drug exposure and hence a higher risk of progression. Methods: We retrospectively evaluated the engraftment kinetics and response outcome of 306 SCTs done at our institution between March 1998 and October 2001. These included patients who had undergone SCT for multiple myeloma (46%), NHL (34%), HD (6%) and AL amyloidosis (14%). Body weight, height, stem cell dose and engraftment data was obtained from medical records. The stem cell dose received was calculated based on their ABW as well as IBW and correlated with the time to white cell and platelet engraftment. We also evaluated the effect of BMI on the progression free survival after the stem cell transplant using various cut offs. Results: The mean (range) for the ABW, IBW and BMI were 46.6 kg to 189 Kg; 45.5 kg to 94 kg; and 17.5 to 55.8 respectively. Using logistic regression, we estimated the ability of CD34 cell dose by actual and ideal body weight to predict the likelihood of platelet engraftment (50,000) by day 21 post transplant. The coefficients using both the doses were very similar (.391 for ideal and 0.361 for actual). Using Receiver operating characteristic analysis (ROC analysis); we determined the stem cell dose cutoff that best predicted for failure to engraft neutrophils by 21 days post transplantation, median CD34 dose by ABW of 3.6 million/Kg and by IBW of 4.2 million/Kg. Similarly, for failure to engraft platelets by day 30 the cutoffs were 2.89 million/Kg by actual weight and 3.77 million/kg by ideal weight. Among the individuals with actual body weight more than 25% of ideal body weight (n=122, 40%), we calculated the optimal total CD34 dose required and compared to the actual dose infused using both the cutoff sets (286 million vs. 446 million, P < 0.001 using ANC cutoff and 251 million vs. 446 million using the platelet cutoff, P < 0.001). We then examined the effect of BMI on progression free and overall survival from transplant. The progression free and overall survival post transplant was similar for patients with BMI over 30 kg/m2 compared to those below this cutoff. There was no difference when patients with myeloma or lymphoma were studied separately. Conclusion: This study, as in previous studies, confirms that stem cell dose determined on the basis of ideal body weight is comparable to that by actual body weight in terms of engraftment kinetics. In patients significantly above the ideal body weight, it is reasonable to use a target based on ideal body weight which will allow for collection of less numbers of CD34 cells, thus conserving resources. Among patient undergoing stem cell transplant, the practice of using corrected ideal body weight does not appear to compromise the outcome of stem cell transplant.

Abstract Background: I-SPY2 is a multicenter, Phase II trial using response-adaptive randomization within biomarker subtypes to evaluate novel agents as neoadjuvant therapy for high-risk at least T2N0 breast cancer. The primary endpoint is pathologic complete response (pCR) at surgery. The goal is to identify regimens that have ≥ 85% Bayesian predictive probability of success in a 300-patient phase 3 neoadjuvant trial defined by hormone-receptor (HR) and HER2 status, and MammaPrint (MP). Regimens may leave the trial for futility (&lt; 10% probability of success), maximum sample size accrual (with probability of success ≥ 10% and &lt; 85%), or as recommended by the independent DSMB. For HER2- subjects the control arm is weekly paclitaxel x12 then doxorubicin & cyclophosphamide (AC) q2-3 weeks x4. For this arm, paclitaxel was omitted and replaced with maximum tolerated dose PARPi talazoparib with synergy dosed irinotecan (25mg/m2). Paclitaxel could be given adjuvantly for these subjects and non-responding subjects could be taken off of experimental therapy. Methods: Women with tumors ≥ 2.5cm were eligible for screening. MP low/HR+ tumors were ineligible. MRI scans (baseline, 3 cycles after start of therapy, prior to AC, and prior to surgery) were used in a longitudinal statistical model to predict pCR for individual patients. Talazoparib was given at 1mg daily with 25mg/m2 irinotecan q2wks. Analysis was intention to treat. Subjects who switched to non-protocol therapy count as non-pCR. Subjects on experimental therapy at time of arm closure are non-evaluable. Talazoparib/irinotecan (TI) was open only to HER2- tumors and eligible for graduation in 3 of 10 pre-defined signatures: HER2-, HR+HER2- and HR-/HER2-. Results: TI did not meet criteria for graduation and was stopped at the recommendation of the DSMB based on expectations of limited activity beyond that seen with standard treatment. Maximum sample size had been reached at the time of this recommendation and subjects currently receiving TI were allowed to continue or change to standard therapy. Exploratory “as treated” analysis for response in gBRCA mutation carriers showed 6/10 gBRCA carriers attained a pCR in the TI arm. Except for 1 patient these gBRCA pCR subjects had &gt;90% tumor reduction by MRI after TI and prior to AC (range: 68-96%). In the TI arm pCR rates were also higher in subjects with a PARPi7-High/MP2 gene expression signature (0.344 vs 0.146). Expected differences in toxicity were seen between arms including g3/4 peripheral neuropathy on control therapy which included paclitaxel (2.6% vs none) and g3/4 neutropenia with TI (30.2% vs 8.2%). Notably gBRCA mutation carriers receiving TI had higher rates of g3/4 neutropenia (60% vs 25.9%). Conclusion: The I-SPY2 study finds the probability that investigational regimens will be successful in a Phase III neoadjuvant trial; TI did not reach the efficacy threshold of 85% probability of success in Phase III in any of the 3 signatures. However by adding talazoparib with synergy dosed irinotecan we were able to omit paclitaxel and observe similar estimated pCR rates. This informs current work to evolve the I-SPY2 trial design to reduce toxicity without compromising outcomes and develop successful combinations targeted to biology, including DNA repair deficiency. Citation Format: Richard Schwab, Amy S. Clark, Christina Yau, Nola Hylton, Wen Li, Denise Wolfe, A Jo Chien, Anne M. Wallace, Andres Forero-Torres, Erica Stringer-Reasor, Rita Nanda, Nora Jaskowiak, Judy Boughey, Tufia Haddad, Heather S. Han, Catherine Lee, Kathy Albain, Claudine Isaacs, Anthony D. Elias, Erin D. Ellis, Payal Shah, Julie E. Lang, Janice Lu, Debasish Tripathy, Kathleen Kemmer, Douglas Yee, Barbara Haley, Melanie Majure, Erin Roesch, Christos Vaklavas, Cheryl Ewing, Teresa Helsten, W Fraser Symmans, Jane Perlmutter, Hope S. Rugo, Michelle Melisko, Amy Wilson, Ruby Singhrao, Laura van 't Veer, Angela DeMichele, Smita Asare, Don Berry, Laura J. Esserman. Evaluation of talazoparib in combination with irinotecan in early stage, high-risk HER2 negative breast cancer: Results from the I-SPY 2 TRIAL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT136.

e23078 Background: There are limited patient (pt) reported outcome data regarding CDDP neurotoxicity. Methods: CDDP-induced peripheral neuropathy was evaluated in pts with testicular cancer planning to receive CDDP (20 mg/m2/d for 5 days) for ≥ 3 cycles. Neurotoxicity was assessed with the EORTC QLQ-CIPN20 tool before each CDDP cycle and every 2-4 months after, out to 18 months. We compared these data to our studies evaluating pts receiving doxorubicin/cyclophosphamide (AC), paclitaxel and oxaliplatin. The total score of the EORTC QLQ-CIPN20, each of the three subscale scores and each individual item was computed following the standard scoring algorithm and converted to a 0-100 scale. Descriptive statistics and graphical plots were utilized. Results: 54 pts receiving CDDP (mean age 33 years) and 18 pts receiving AC were evaluated. Following completion of CDDP, neuropathy symptoms (sensory neuropathy score and numbness/tingling in toes/feet) worsened for about 6 months (consistent with the so-called “coasting phenomena”), similar to what had previously been seen with oxaliplatin (but different than what had been seen with paclitaxel). For CDDP pts, during therapy, numbness and tingling in fingers/hands were more prominent, than the same symptoms in the toes/feet. After therapy was completed, numbness, and tingling became more prominent in toes/feet, but improved in the fingers/hands. After stopping therapy, shooting/burning pain did not worsen in upper or lower extremities. During therapy, CDDP pts had less problems than had previously been seen with oxaliplatin or paclitaxel, maybe because of the younger ages of the CDDP pts. With AC, all of the CIPN-20 sensory neuropathy scores were better than was seen in the pts receiving CDDP and also in pts receiving paclitaxel and oxaliplatin in previous evaluations. Conclusions: CDDP-induced neuropathy is more similar to oxaliplatin-induced neuropathy than paclitaxel-induced neuropathy. AC chemotherapy pts do not have substantial changes in CIPN 20 scores, consistent with the CIPN 20 instrument being a measure of chemotherapy-induced neuropathy, as opposed to more general chemotherapy-induced toxicities. Clinical trial information: NCT02677727.

Purpose: The purpose of this article is to provide a data-driven set of best practices to consider in the management of diabetic macular edema (DME). Methods: The current discussion and recommendations represent the authors’ interpretations of data from selected references based on perceived relevance and study design. Results: DME is a common cause of visual impairment globally. The underlying progressive retinal microvascular damage is associated with upregulation of VEGF and a multitude of other inflammatory pathways. Three clinically relevant subcategories of DME can be identified: central-involved DME (CIDME) with preserved visual acuity, CIDME with associated visual loss, and non-CIDME. Management approaches may include observation, laser photocoagulation, intravitreal pharmacotherapy with anti-VEGF agents or corticosteroids, or a combination of these, and may vary depending on the specific type of DME and associated severity of diabetic retinopathy. Additional factors to consider in the management of patients with DME include the appropriate use of imaging and recognition of the chronic nature of the underlying disease process in many eyes. Conclusions: DME management is complex. Intravitreal pharmacotherapies are the current cornerstone of treatment for CIDME and appear poised to remain so for the foreseeable future.

53 Background: The National Academy of Medicine recommends interprofessional collaboration to promote optimal patient- and family-centered care. We sought to understand whether medical and psychosocial professionals who participated in an interprofessional communication intervention perceived it as distinct from usual clinical care. Methods: Our intervention targeted “medical” (physicians, nurse practitioners) and “psychosocial” (social workers, psychologists) professionals. It consisted of an interprofessional family conference, using a structured conversation guide, conducted during the first 6 months of a child’s cancer care. Conferences aimed to enable families to share hopes and worries and ask questions about their child’s care. Clinicians received a 60-minute training focused on communication skills, such as eliciting families’ hopes and worries, and suggested approaches to collaborating during conferences. Clinicians participated in debriefing interviews after each conference (range 1-3). Three of us conducted thematic analysis of interview data. Results: Twenty-two professionals (6 attending MDs, 4 fellow MDs, 8 NPs, and 8 psychosocial clinicians) gave 34 interviews. Medical and psychosocial professionals described interprofessional family conferences as distinct from usual practice patterns, largely due to their interprofessional colleagues’ presence. This co-presence contributed to “being on the same page.” Conferences sometimes bred a new understanding of a family’s needs and consequent care changes. However, both medical and psychosocial professionals noted that psychosocial professionals often were not vocal contributors to the conference. Some psychosocial clinicians reported being unsure of “the rules.” Conclusions: An interprofessional communication intervention promoted shared understanding between interprofessional colleagues. However, medical professionals were described as more vocal, perhaps due to insufficient role clarity or medical dominance.