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Relapsed and refractory multiple myeloma (RRMM) is a plasma cell neoplasm defined by progressively refractory disease necessitating chronic and increasingly intensive therapy. Despite recent advances, limited treatment options exist for RRMM. This single-arm, open label phase 1 study aimed to evaluate the safety of novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T construct that leverages a completely synthetic antigen-binding domain (CART-ddBCMA), which was specifically engineered to reduce immunogenicity and improve CAR cell surface stability. Thirteen patients ≥18 years with RRMM who received at least 3 prior regimens of systemic therapy were enrolled in the study. Patients received a single dose of 100 × 106 CART-ddBCMA (DL1) or 300 × 106 CART-ddBCMA (DL2) following standard lymphodepleting chemotherapy. The primary endpoints of the study were to evaluate the incidence of treatment emergent adverse events, including dose-limiting toxicities, and establish a recommended phase 2 dose. Results showed that CART-ddBCMA was well tolerated and demonstrated a favorable toxicity profile. Only 1 case of grade ≥3 cytokine release syndrome and 1 case of immune effector cell–associated neurotoxicity were reported; both were at DL2 and were manageable with standard treatment. No atypical neurological toxicities and Parkinson disease-like movement disorders were observed. The maximum tolerated dose was not reached. All infused patients responded to CART-ddBCMA, and 9/12 (75%) patients achieved complete response/stringent complete response. Responses deepened over time, and at the time of last data-cut (median follow-up 56 weeks), 8/9 (89%) evaluable patients achieved minimal residual disease negativity. In conclusion, the findings demonstrate the safety of CART-ddBCMA cells and document durable responses to CART-ddBCMA in patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT04155749.

Although caregivers of patients with multiple myeloma (MM) play a critical role in supporting their loved ones throughout the illness course, studies examining caregiver quality of life (QOL), psychological distress, and prognostic awareness are lacking. We conducted a cross-sectional, multisite study of patients undergoing treatment with MM and their caregivers. Eligible caregivers were enrolled to 1 of 3 cohorts based on lines of therapy. Caregivers completed validated questionnaires to assess their QOL, psychological distress, and perceptions of prognosis. We enrolled 127 caregivers of patients with MM (newly diagnosed [n = 43], 2-3 lines of therapy [n = 40], and ≥4 lines of therapy [n = 44]). Caregiver QOL and psychological distress did not differ by line of therapy. The rate of clinically significant anxiety, depression, and posttraumatic stress disorder symptoms were 44.1% (56/127), 15.8% (20/127), and 24.4% (31/127), respectively. When examined in dyads, caregivers reported higher rates of clinically significant anxiety (44.4% [55/124] vs 22.5% [28/124]) compared with patients with MM. Most caregivers (84.2%, 101/120) reported that the oncologist had informed them that the patient’s cancer was incurable; however, only 50.9% (58/114) and 53.6% (59/110) of caregivers acknowledged the patient’s cancer was terminal and incurable, respectively. Caregivers of patients undergoing treatment for MM experience substantial psychological distress across the disease continuum, particularly anxiety. The majority of caregivers of patients with MM report that knowing the patient’s prognosis is extremely important and report that the oncologist told them that the patient was incurable. Nevertheless, a significant portion of caregivers believe that the patient’s MM is curable.

Background: Prior, retrospective analysis of nightly fasting among women with breast cancer suggests that fasting less than 13 hours per night may be associated with higher risk of breast cancer recurrence. Small studies suggest that fasting duration can influence inflammation, obesity, sleep, and other potential mediators of breast cancer recurrence risk. Prolonged overnight fasting is a simple, nonpharmacological behavioral intervention strategy that may be doable for most patients. We designed this pilot study to prospectively evaluate the feasibility of prolonged overnight fasting among breast cancer survivors. Methods: We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 hours overnight for a 12-week period among women with a history of early stage breast cancer (I to III) who had completed initial cancer therapy at least 6 months prior. Baseline and end of study assessments included measurements of body mass index (BMI), quality of life (QOL) (Functional Assessment of Cancer Therapy - General (FACT-G)), mood (Hospital Anxiety and Depression Scale (HADS)), fatigue (Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue), levels of physical activity (Godin Leisure-Time Exercise Questionnaire), and blood biomarkers (expanded lipid profile, hemoglobin A1c, C-reactive protein, interleukin-6, tumor necrosis factor alpha, leptin, adiponectin). Patient-reported outcome (PRO) surveys were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting in the food diary for 13 hours on at least 70% of nights during the study period. Changes in study measures from baseline were evaluated using Wilcoxon signed-rank tests. Results: Between July 2020 and January 2021, we enrolled 40 women with a history of breast cancer. Participants had a median age of 59.9 (range 34.9-76.3) and median time since diagnosis was 4.5 years (range 0.8-20.7). At baseline, BMI was normal (18.5-24.9) in 40.0%, overweight (25-29.9) in 37.5%, and obese (≥30) in 22.5%. Forty-two and a half percent had Stage I cancer, 42.5% stage II, and 15.0% stage III. Sixty-five percent were on hormonal therapy. Ninety-five percent of participants fasted ≥ 13 hours for at least 70% of study days (95% CI 83%-99%). At 6 weeks, there was a statistically significant improvement in anxiety (p=.0007). No other significant changes were seen in PROs. At 12 weeks, there were statistically significant improvements in BMI (p=.0072), anxiety (p=.0141), depression (p=.0048), and fatigue (p=.0105). There was no association between change in BMI during the study and baseline BMI category, age, or endocrine therapy. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks. Conclusions: Prolonged overnight fasting is feasible in the breast cancer population and may improve BMI, mood, and fatigue without a detrimental effect on overall QOL. The data from this study support the need for a larger, longer randomized study of prolonged overnight fasting in the breast cancer population to further evaluate the effects on body composition, mood, QOL, metabolic markers, and risk of recurrence. Table 1.Impact of Prolonged Overnight Fasting among Breast Cancer SurvivorsStudy AssessmentMedian at baselineMedian at 12 weeksMedian within-participant changep-valueBody Mass Index (kg/m2)26.4225.80-0.380.0072HADS - Depression1.001.00-1.000.0048HADS - Anxiety4.504.00-0.500.0141FACIT - Fatigue47.5049.821.000.0105FACT-G - Quality of Life95.2096.840.910.4933Physical Activity Level40.5039.000.000.3340Hemoglobin A1c (mg/dL)5.455.400.000.2758High-density lipoprotein (mg/dL)72.0073.00-2.000.4688Low-density lipoprotein (mg/dL)92.0099.001.000.5626Total Cholesterol (mg/dL)193.00192.003.000.6569C-reactive protein (mg/L)1.500.90-0.100.1043Interleukin-6 (pg/mL)2.001.90-0.300.1213Tumor Necrosis Factor α (pg/mL)0.740.74-0.050.2898Adiponectin (ug/mL)12.0012.000.000.0682Leptin (ng/mL)7.158.30-0.100.8418 Citation Format: Elizabeth K. O'Donnell, Yael N. Shapiro, Amy Comander, Steven J. Isakoff, Beverly Moy, Laura Spring, Seth Wander, Irene Kuter, Jennifer Shin, Jerry Younger, Michelle Specht, Chryssanthi Kourniotis, Carol Sullivan, Loren Winters, Nora Horick, Jeffrey Peppercorn. Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-11.

Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and perceptions of prognosis by line of therapy are lacking.The authors conducted a cross-sectional, multisite study of patients undergoing treatment for MM (excluding maintenance) between June 2020 and January 2021. The authors conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2 to 3 lines; and 3) 4 or more lines. Patients completed validated questionnaires to assess their QOL, fatigue, psychological distress, and perceptions of prognosis.A total of 180 patients with MM were enrolled (newly diagnosed [n = 60], 2 to 3 lines [n = 60], and ≥4 lines of therapy [n = 60]). QOL, symptom burden, and fatigue scores did not differ by lines of therapy. There were no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post-traumatic stress disorder symptoms were 23.9% (43 of 180), 23.9% (43 of 180), and 24.4% (44 of 180), respectively. Most patients (84.7%, 149 of 176) reported that their oncologist told them their cancer was incurable, but only 30.6% (53 of 173) acknowledged that they were terminally ill, and 42.0% (73 of 174) reported that they thought their cancer was incurable.Patients with MM undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, regardless of line of therapy. A substantial proportion of patients with MM have significant misperceptions about their prognosis and the curability of their illness despite reporting being informed of the prognosis by their oncologist.This study discusses 180 patients with MM (newly diagnosed [n = 60], 2-3 lines [n = 60], and ≥4 lines of therapy [n = 60]). Quality of life, symptom burden, and fatigue scores do not differ by lines of therapy. There are also no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post-traumatic stress disorder symptoms are 23.9%, 23.9%, and 24.4%, respectively. Most patients (84.7%) report that their oncologist told them their cancer was incurable, but only 30.6% acknowledge that they are terminally ill, and 42.0% report that they thought their cancer was incurable.

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

Introduction: Blood-based multi-cancer early detection (MCED) tests in development may substantially expand the number of “screenable” cancers. Defining an optimal approach for tissue of origin (TOO) localization in individuals with cancer-suspected MCED results is critical. Two recent prospective trials employed differing and distinct approaches for conducting TOO evaluation. The PATHFINDER study conducted molecular TOO testing for localization and DETECT-A used upfront neck-to-thigh imaging-first to rule-in or rule-out and then to localize the cancer. Using mathematical modeling, we examined the diagnostic burden of each approach. Methods: Building upon a published quantitative framework, a mathematical expression for diagnostic burden was derived as a function of positive predictive value (PPV) of the detection module, TOO accuracy of the localization module, and number of procedures associated with each diagnostic outcome; the latter were estimated from established clinical guidelines with diagnostic procedures narrowly selected for molecular TOO calls. We then explored the relationship between PPV, TOO accuracy, and diagnostic burden. Imaging and molecular TOO strategies were compared by estimating absolute difference in diagnostic burden across a range of performance levels. Results: With a molecular TOO strategy we estimate 2.1 procedures to reach diagnostic resolution for correctly-localized true positives, 4.4 for incorrectly-localized true positives, and 4 for false positives; with imaging TOO, 2.75 procedures for true positives and 2.4 for false positives. Across the entire spectrum of performance for both detection and localization, a strategy with molecular TOO resulted in a mean diagnostic burden of 3.6 (Var 0.198); with imaging TOO, 2.6 (Var 0.010). The breakeven curve defined by zero absolute difference between strategies shows that molecular TOO has lower burden for only 4.5% of all possible PPV and TOO accuracy combinations and that 79% PPV is required for a 90% accurate molecular TOO strategy to be less burdensome than imaging TOO. Conclusions: This analysis demonstrates that imaging TOO is more efficient than molecular TOO across 95.5% of all possible PPV and TOO accuracy combinations. Molecular TOO can reduce diagnostic burden when localization accuracy is very high or overall test PPV is very high. This analysis highlights the need for ongoing innovation in cancer detection and cancer localization as separable parts of the MCED test. In summary, the use of advanced imaging first to determine TOO as part of an MCED screening approach is likely less burdensome than a broad molecular TOO approach, although a nuanced approach to molecular TOO based on probability and type of cancer may contribute to diagnostic efficiency. Citation Format: Christopher Tyson, Elizabeth K. O'Donnell, Elliot Fishman, Vijay Parthasarathy, Tomasz M. Beer. Evaluating the diagnostic burden of tumor localization strategies for multi-cancer early detection tests [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 769.

Multiple myeloma (MM), a plasma cell malignancy, accounts for ~10% of hematologic malignancies and predominantly affects the older population. It exhibits a heterogeneous biology and a complex genetic phenotype that affect patient prognosis. The treatment of MM has evolved significantly over the last decade with the use of autologous stem cell transplantation and several novel agents. Consequently, outcomes have improved in this time period, with the most impact in younger patients. Management of MM in elderly frail patients requires a thoughtful approach as majority of these patients carry multiple comorbidities and are precluded from high-dose chemotherapy and autologous stem cell transplantation-accounting for the more modest improvement in outcomes. Assessing transplant eligibility and performance status is a critical first step. Subsequently, the choice of frontline therapy in transplant-ineligible frail patients must balance efficacy with adverse effects to optimize quality of life. Here, we review the current state of induction regimens in this patient population.

Interrogation of cell-free DNA (cfDNA) represents an emerging approach to non-invasively estimate disease burden in multiple myeloma (MM). Here, we examined low-pass whole genome sequencing (LPWGS) of cfDNA for its predictive value in relapsed/ refractory MM (RRMM). We observed that cfDNA positivity, defined as ≥10% tumor fraction by LPWGS, was associated with significantly shorter progression-free survival (PFS) in an exploratory test cohort of 16 patients who were actively treated on diverse regimens. We prospectively determined the predictive value of cfDNA in 86 samples from 45 RRMM patients treated with elotuzumab, pomalidomide, bortezomib, and dexamethasone in a phase II clinical trial (NCT02718833). PFS in patients with tumor-positive and -negative cfDNA after two cycles of treatment was 1.6 and 17.6 months, respectively (HR 7.6, P 0.0001). Multivariate hazard modelling confirmed cfDNA as independent risk factor (HR 96.6, P = 6.92e-05). While correlating with serum-free light chains and bone marrow, cfDNA additionally discriminated patients with poor PFS among those with the same response by IMWG criteria. In summary, detectability of MM-derived cfDNA, as a measure of substantial tumor burden with therapy, independently predicts poor PFS and may provide refinement for standard-of-care response parameters to identify patients with poor response to treatment earlier than is currently feasible.

Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and prognostic awareness by line of therapy are lacking. Methods: We conducted a cross-sectional, multi-site study of patients undergoing treatment for MM (excluding maintenance therapy) between 6/2020-1/2021. To capture the full spectrum of treatment, we conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; and 3) ≥ 4 lines. Patients completed validated questionnaires to assess their QOL, symptom burden, fatigue, psychological distress, and perceptions of prognosis. We used multivariate linear regression models to examine the association between lines of therapy, QOL, psychological distress, with patient's perception of their prognosis. Results: We enrolled 180 patients with MM (newly diagnosed (n=60), 2-3 lines (n=60), and ≥4 lines of therapy (n=60)). QOL and fatigue scores did not differ by lines of therapy: (QOL: 116.6 (SD=20.6) vs. 112.3 (SD=28.2) vs. 110.6 (SD=29.6); Fatigue: 36.9 (SD=9.9) vs. 35.4 (SD=11.9) vs. 33.7 (SD=12.5). There were also no statistically significant differences in depression, anxiety, or PTSD symptoms by line of therapy. The rate of clinically significant depression, anxiety, and PTSD symptoms were 23.9% (43/180), 23.9% (43/180), and 24.4% (44/180), respectively. Overall, 84% (147/175) of patients reported that it is 'extremely' or 'very' important to know about their prognosis, and the majority (66.1%, 117/177) stated that they had received adequate information regarding their prognosis. Patients reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (93.4%, 155/166), coping with the disease (87.4%, 145/166), and preparing for the future (86.8%, 144/166). Most patients, 84.7% (149/176) reported that their oncologist told them their cancer was incurable but only 30.6% (53/173) acknowledged that they were terminally ill and only 42.0% (73/174) reported that they thought their cancer was incurable . Patients receiving 2-3 lines of therapy were more likely to acknowledge their terminal illness (36.7% vs. 19.6%, p=0.045) and that their MM was incurable (90.0% vs. 75.9%, p=0.047) compared to those receiving 1 st line therapy. QOL and psychological distress were not associated with patient's perception that their MM was incurable. However, patients who acknowledged their terminal illness reported higher depression (B=1.52, P = 0.009), anxiety (B=1.52, P=0.0037), symptom burden (B=7.42, P=0.007), and lower QOL (B=-14.78, p=0.001). Conclusions: MM patients undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, irrespective of their line of therapy. Although the majority reported that their oncologist had told them that their cancer is incurable, a substantial proportion still reported that they believed they were curable. Acknowledgement of terminal illness was associated with higher rates of psychological distress and symptoms burden and lower QOL. Interventions are needed to improve patients' QOL, reduce their psychological distress, and cultivate adaptive coping strategies that may help improve the patient experience over the MM disease course. Disclosures O'Donnell: Adaptive: Consultancy; Oncopeptide: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Karyopharm: Consultancy. Nadeem: Bristol Myer Squibb: Consultancy; GSK: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy. Yee: Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; GSK: Consultancy; Oncopeptides: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Janssen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Epizyme: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Eli Lilly: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munshi: Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Legend: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Adaptive Biotechnology: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AbbVie: Consultancy; Takeda: Consultancy, Research Funding; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; AstraZeneca: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; Regeneron: Consultancy; Secura Bio: Consultancy; Celgene/BMS: Consultancy, Research Funding; Sanofi: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Although caregivers of MM patients play a critical role in supporting their loved ones throughout the illness course, studies examining caregiver quality of life (QOL), psychological distress, and prognostic awareness are lacking. Methods: We conducted a cross-sectional, multisite study of patients undergoing treatment with MM (excluding maintenance therapy) and their caregivers between 6/2020-3/2021. Eligible caregivers were identified by the patient as the primary caregiver and enrolled to 1 of 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; 3) ≥4 lines of therapy. Caregivers completed validated questionnaires to assess their QOL, psychological distress, and perceptions of prognosis. Patients also completed validated questions to assess their perception of prognosis. We used descriptive statistics to describe caregiver QOL, psychological distress, and perception of prognosis. We then descriptively compared psychological distress and perception of prognosis between patient and caregiver dyads. Results: We enrolled 127 caregivers of MM patients (newly diagnosed (n=43), 2-3 (n=40), and ≥ 4 lines of therapy (n=44)). Median caregiver age was 61.8 years (range 24.0-81.9); 71.7% (91/127) were female; and 68.5% (87/127) were taking care of their spouse/partner. Caregiver QOL and psychological distress did not differ by lines of therapy. The rate of clinically significant depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms were 15.8% (20/127), 44.1% (56/127), and 24.4% (31/127), respectively. When examining dyads, caregivers reported higher rates of clinically significant anxiety symptoms (44.4% vs. 22.5%) compared to MM patients. Caregivers reported less clinically significant depression symptoms (15.3% vs. 24.2%) and similar rates of clinically significant PTSD symptoms (24.2% vs 25.0%). Overall, 89.6% (112/125) of caregivers reported that it is 'extremely' or 'very' important to know about the patient's prognosis and 55.6% (70/126) stated that they had received adequate information regarding the patient's prognosis. Caregivers reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (94.0%, 109/116), preparing for the future (88.6%, 101/114), and coping with the disease (85.2%, 98/115). Most caregivers (84.2%, 101/120), reported that the oncologist had told them the patient's cancer was incurable. In contrast, only 53.6% (59/110) of caregivers reported that they thought the patient's cancer was incurable and 37.9% (58/114) acknowledged that the patient is terminally ill. Caregiver demographics, line of therapy, QOL, and psychological distress were not associated with their perceptions of the patient's prognosis. When examined in dyads, caregivers were more likely to report that the patient is terminally ill (50.1% vs. 30.1%). There was no difference in caregivers' and patients' report that the oncologist said MM is incurable (83.3% vs. 84.2%). Conclusions: Caregivers of patients undergoing treatment for MM experience substantial psychological distress across the disease continuum, particularly anxiety. Supportive care interventions are needed to improve caregivers' QOL and to reduce their psychological distress. Although the majority of caregivers of MM patients report that knowing the patient's prognosis is extremely important and report that the oncologist told them that the patient was incurable, a significant portion of caregivers report that the patient is curable. Interventions are needed to promote effective coping and to enhance caregiver's perception of the patient's prognosis to facilitate informed-decision making. Disclosures O'Donnell: Janssen: Consultancy; Takeda: Consultancy; Oncopeptide: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Bristol Myer Squibb: Consultancy. Nadeem: Takeda: Consultancy; Bristol Myer Squibb: Consultancy; GSK: Consultancy; Karyopharm: Consultancy; Adaptive: Consultancy. Yee: Karyopharm: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; Amgen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: 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; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Eli Lilly: Consultancy. Munshi: Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Abbvie: Consultancy; Legend: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AstraZeneca: Consultancy; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; Karyopharm: Consultancy, Research Funding; Secura Bio: Consultancy; Sanofi: Consultancy; Regeneron: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

Exercise is recommended for all patients with cancer, but there has been limited study of exercise habits in patients across the spectrum of illness.This pragmatic survey aimed to identify the unmet supportive care needs, self-reported symptoms, and exercise habits among both cancer survivors and patients living with advanced disease to determine adherence to exercise guidelines and to identify barriers and opportunities to improve exercise.An anonymous cross-sectional self-administered paper survey was distributed to patients with cancer presenting for oncology clinic visits at an academic cancer center. Survey measures included presence of symptoms and health problems in addition to weekly time spent exercising, change in exercise levels since diagnosis, interest in exercise, and self-reported barriers. Participants reporting at least 150 min of exercise per week were characterized as adherent to guidelines.Among 640 survey respondents, 570 (89%) completed questions about exercise. Only 44% of cancer survivors and 34% of patients living with advanced disease met current guidelines. Survivors who met exercise guidelines had a lower prevalence of fatigue and memory impairments, but this finding was not seen among patients with advanced cancer. Over 70% of patients with advanced disease and 47% of survivors reported decreasing exercise post-diagnosis compared to pre-diagnosis. Prominent barriers to exercise among both groups included burden of illness and time constraints but interest in increasing exercise was high.There is an opportunity to improve exercise and related outcomes among a large percentage of both cancer survivors and patients living with advanced disease.

Bone involvement manifesting as osteolytic bone disease (OBD) or osteopenia is one of the defining features of multiple myeloma (MM). Osteolytic lesions develop in nearly 90% of patients with MM, and these are frequently complicated by skeleton-related events (SREs) such as severe bone pain, pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord compression. SREs have a negative effect on patients' quality of life and affect their long-term outcomes, including survival. In MM, the delicate balance between bone formation and bone destruction is perturbed. OBD is a consequence of increased osteoclast activation along with osteoblast inhibition, which alter bone remodeling. Although MM remains incurable, tremendous progress has been made in the treatment of the disease. As such, there is a need to address the symptoms of the disease that affect quality of life and, ultimately, overall survival. Novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM itself. In addition to bisphosphonates, several novel agents are currently under investigation for their positive effect on bone remodeling via osteoclast inhibition or osteoblast stimulation. Future studies will look to combine or sequence all of these agents to improve quality of life, decrease the symptoms of MM OBD, and enhance antitumor activity.

Introduction: PVX-410 Multi-Peptide Vaccine (OncoPep, Inc.) is being developed for the treatment of SMM. PVX-410 consists of 4 human leukocyte antigen-A2 (HLA-A2), synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic). Adults with SMM at high risk of progression to active MM who were HLA-A2-positive were eligible. The primary objective was to determine the tolerability of PVX-410, initially as monotherapy and then in combination with lenalidomide (len). Immune and disease response also were assessed. Methods: All patients received 6 bi-weekly subcutaneous injections of PVX-410, initially at the low-dose of 0.4 mg (0.1 mg/peptide or 0.4 mg total) and then at the target dose of 0.8 mg (0.2 mg/peptide or 0.8 mg total). In the PVX-410+len cohort, patients received 3 standard cycles of len (25 mg orally on Days 1-21 every 28 days, without dexamethasone). All patients also received 0.5 mL (1 mg) Hiltonol® (poly-ICLC) (2 mg/mL) via intramuscular injection at the time of PVX-410 administration. Patients were followed for 12 months post-treatment. Blood samples for immune response evaluation were collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 weeks during treatment and at Months 1, 3, 6, 9, and 12 post-treatment. Disease response was assessed at the same time points, except Weeks 0 and 2, using International Myeloma Working Group and modified European Group for Blood and Bone Marrow Transplant criteria. Results: Overall, 22 patients with high-risk SMM were enrolled (age range 39 to 82 years), of whom 12 received PVX-410 monotherapy (3 low-dose; 9 target dose) and 10 received PVX-410 (target dose) + len. All 22 patients have either completed the study through post-treatment Month 12 (N=15) or discontinued before that time (N=7). PVX-410 was well-tolerated, with a treatment-emergent adverse event (TEAE) profile consistent with that expected, based on previous clinical studies with peptide vaccines. All (100%) 22 patients experienced at least 1 TEAE. Among monotherapy patients, the most common TEAEs were injection site pain (50%); fatigue (33%); and injection site erythema, pyrexia, and rash (each 25%). The TEAE profile of PVX-410+len was generally similar to that see with PVX-410 alone, although the incidence of commonly reported TEAEs was higher with the combination than with PVX-410 alone. The majority of TEAEs were Grade 1 in intensity and occurred within 2 days after study vaccine injection. No deaths or study drug-related serious adverse events were reported. PVX-410 was immunogenic as monotherapy (10/11 patients) and in combination with len (9/9), as demonstrated by an increase in the percentage of tetramer+ cells (≥1.5-fold increase over baseline) and interferon-gamma+ (IFN-γ) cells (≥2.0-fold increase over baseline) in the CD3+CD8+ cell population. This increase was statistically higher for IFN-γ+ cells after 2 vaccinations in the combination group. The CD8+ T-lymphocyte response was also characterized by increases from baseline in interleukin-2-, tumor necrosis factor-alpha-, and CD137-positive cells in both treatment groups. Furthermore, decreases in the naïve memory cell population and increases in the effector memory cell population were seen post-vaccination; this response was enhanced by the addition of len. Among the 12 monotherapy patients, 5 (2 low-dose; 3 target-dose) experienced progression to active disease within 9 months post-treatment, and 7 had stable disease (SD) at follow-up Month 12. Among the 9 evaluable PVX-410+len patients, 5 achieved at least a minimal response, with 1 patient achieving a partial response; 1 of these 5 patients then progressed to MM by Month 5 post-treatment. Four patients had SD at follow-up Month 12. Conclusions: Six doses of PVX-410 were well tolerated in 22 patients with high-risk SMM, with an expected AE profile both as monotherapy and in combination with len. An immune response to PVX-410 was seen with PVX-410 alone, which was enhanced by the addition of len. Based on these promising findings to date, investigation of PVX-410 in combination with immunogenic agents is continuing. Disclosures Nooka: Spectrum, Novartis, Onyx pharmaceuticals: Consultancy. Wang:Acerta: Consultancy, Research Funding; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding; BeiGene: Research Funding; Juno Therapeutics: Research Funding; Kite Pharma: Research Funding; Dava Oncology: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana BioSciences: Research Funding. Kaufman:Incyte: Consultancy; Pharmacyclics: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Peterkin:OncoPep: Employment. Lonial:Celgene: Consultancy; Onyx: Consultancy; Janssen: Consultancy; BMS: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Millenium: Consultancy. Richardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Raje:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Eli Lilly: Research Funding.

Methods: As reported previously, PVX-410 Multi-Peptide Vaccine (OncoPep, Inc.) is being developed for the treatment of SMM. PVX-410 consists of 4 human leukocyte antigen-A2 (HLA-A2), synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic). Adults with SMM at high risk of progression to active MM and were HLA-A2-positive were eligible. The primary objective of this study was to determine the tolerability of PVX-410, initially as monotherapy. Immune response and change in M protein and free light chain ratio (FLC) were also assessed. PVX-410 alone was safe and immunogenic in the initial 12 patients treated, with all 12 having positive immune response to at least 1peptide, as determined by interferon-gamma enzyme-linked immunosorbent spot (Elispot) and tetramer assays. Given its immunomodulatory properties, it was hypothesized that co-administration of lenalidomide (len; Celgene Corporation) would enhance the T cell-mediated immune response induced by PVX-410. Accordingly, the tolerability, immunogenicity, and anti-MM activity of PVX-410+len was then investigated. Results in the PVX-410 alone cohort were previously reported. In the PVX-410+len cohort, patients received a dose of PVX-410, 0.8mg (0.2mg/peptide / 0.8mg total dose) subcutaneously plus 0.5 mL (1mg) Hiltonol® (poly-ICLC; Oncovir, Inc.) intramuscularly every 2 weeks for a total of 6 doses with 3 standard cycles of len (25 mg orally) on Days 1-21 every 28 days, without dexamethasone. Patients are followed for 12months post-treatment. Blood samples for immune response evaluation are collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 during treatment and at Months 1, 3, 6, 9, and 12 post-treatment. Disease response is assessed at the same time points, except Weeks 0 and 2, using International Myeloma Working Group and modified European Group for Blood and Bone Marrow Transplant criteria. Results: Overall, 22 patients have been enrolled, with ages ranging from 39 to 82 years. Ten patients were enrolled in the PVX-410+len cohort, with 9 evaluable for response. All 10 patients received at least 1 cycle of len; 8 received all 3 cycles; 1 received 1 cycle before discontinuing due to a deviation; and 1 completed 2 cycles as of the cutoff date. One patient had 7 of 21 planned doses held due to neutropenia related to lenalidomide, but resumed the next cycle at a reduced dose (from 25 mg to 20 mg). Immunogenicity data with PVX-410+len and PVX-410 alone, as determined via intracellular cytokine staining and tetramer analysis, will be presented. With PVX-410 alone, 5 patients, 2 of 3 with the low-dose of 0.4 mg (0.1mg/peptide) and 3 of 9 at the target-dose (0.2 mg/peptide), experienced progression to active disease within 9 months post-treatment, and 7 had stable disease (SD) at the last follow up visit in the 12 month follow up period. With PVX-410+len, 5 patients have experienced partial or minimal responses and 3 have experienced SD. Durability of response is assessed through the 12-month study period; 1 patient has progressed to active myeloma during this time. PVX-410 was well-tolerated alone and with len. Most adverse events (AEs) have been ≤Grade 2 and non-serious. AEs seen more frequently with PVX-410+len versus PVX-410 alone are expected with len and include hematologic abnormalities (neutropenia, anemia, thrombocytopenia), gastrointestinal disorders (nausea, diarrhea, constipation), skin and cutaneous disorders (rash, pruritus), and myalgia. There was 1serious AE in the combination cohort (pneumonia), considered possibly related to len and unrelated to PVX-410. Conclusions: Six doses of PVX-410 were well tolerated in 22 patients with SMM. Additional AEs seen with PVX-410+len versus PVX-410 alone were expected with the addition of len to the treatment regimen. An immune response to the vaccine was seen in all patients treated with PVX-410 alone and is expected to be enhanced with PVX-410+len; these data will be presented. Based on the promising findings to date, an evaluation of PVX-410 in combination with an antibody to the programmed cell-death-1-ligand complex (PD1/PDL1) is planned to begin in 2015. Disclosures Nooka: Spectrum Pharmaceuticals: Consultancy; Onyx Pharmaceuticals: Consultancy. Off Label Use: Off label use of lenalidomide. Wang:Janssen: Honoraria; Pharmacyclics, Janssen, Celgene, Oncopep, Kite, Juno: Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding. O'Donnell:Millennium: Consultancy. Shah:Millenium: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Array: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Lonial:Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Richardson:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Raje:Takeda: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy; Amgen: Consultancy; Onyx: Consultancy; AstraZeneca: Research Funding; Millenium: Consultancy; Novartis: Consultancy; Acetylon: Research Funding; Eli Lilly: Research Funding.