639 Background: EOPC, defined as pancreatic cancer (PC) diagnosed at 60 years of age or younger, is associated with significant life years lost. Approximately 5-10% of average-onset PC have an underlying germline etiology. Currently NCCN & ASCO guidelines recommend germline testing in all pts w PC. However, there is limited data regarding to what extent pts with EOPC pursue recommended germline testing. We examined the findings from genetic evaluation in EOPC. Methods: A retrospective review of EOPC pts at the Levine Cancer Institute who underwent clinical genetic assessment between January 2019 and December 2021 was performed. Data on clinicodemographic, family history, and genetic testing results were obtained and analyzed descriptively. Results: We identified 69 EOPC pts who were evaluated by genetics. Baseline characteristics include median age of 55 years (range 25-60) with 52% male, 48% white, 23% black, and 52% with current or prior tobacco use. At presentation, 41% and 59% had metastatic and non-metastatic disease, respectively. Eight (12%) pts declined germline testing. Among the 61 who underwent germline testing, 30 (49%) pts had negative testing, 21 (34%) had only variants of uncertain significance, and 10 (16%) had pathogenic/likely pathogenic germline variants (PVs). The most frequently seen PVs were ATM (20%), BRCA1 (20%), BRCA2 (10%), MLH1 (10%), NTHL1 (10%), PTCH1 (10%), CFTR (10%) and one (10%) with multiple pathogenic germline findings including RAD51 and BRCA1. Among the 10 pts with PVs, only two reported any first or second-degree family members with cancer. Conclusions: In this cohort of EOPC at a large community multi-site cancer center, 16% of patients had germline PVs, higher than reported in older patients with PC. Only 20% of pts w PVs reported first or second-degree family members with cancer and highlights the importance to recommend germline testing independent of family history even among EOPC cohorts. Further investigation to clarify reasons for refusal of germline testing in EOPC should be evaluated.

Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering cell cycle arrest and the death of malignant cells. Multiple Myeloma (MM) patients with del17p are deficient in TP53 and have a particularly poor prognosis. Given its unique mechanism of action, we investigated whether Seli has increased efficacy in RRMM patients with del17p compared to other high-risk cytogenetics (OHRC). This is an IRB-approved observational study of RRMM patients with high-risk cytogenetics (del17p, t (4;14), t (14;16) or gain 1q) or standard-risk cytogenetics treated at the Levine Cancer Institute (LCI) with a Seli-based regimen between January 2019 and December 2022. Time-to-event endpoints (PFS, OS) were evaluated using Kaplan–Meier (KM) methods. Log-rank tests compared time-to-event endpoints between cohorts [del17p vs. OHRC vs. standard risk]. We identified 40 RRMM patients with high-risk cytogenetics, including 16 patients with del17p and 24 patients with OHRC, as well as 20 with standard-risk cytogenetics. The median age was 62.5 vs. 69 vs. 65.5 years (del17p group vs. OHRC vs. standard risk). The median prior line of therapies was five (range: 3–16) with similar rates of prior autologous stem cell transplant in all arms (68.8% vs. 62.5% vs. 70.0%). The most frequently used regimens were Seli–Pomalidomide–dexamethasone(dex) or Seli–Carfilzomib–dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. The median time to start the Seli-based regimen after initial MM diagnosis was 5.6 years for the del17p group, 4.1 years in OHRC, and 4.8 years in the standard-risk group. The median follow-up time after the start of the Seli-based regimen was 10.5 months (mos) in the del17p group, 8.4 mos in OHRC, and 10.3 mos in the standard-risk group. In the del17p group, 50% had an objective response, 41.7% in the OHRC, and 35% in the standard-risk group (p = 0.71). Depth of response was also similar across the arms (12.5% vs. 12.5% vs. 10.0% VGPR p = 0.99). The median OS was 10.9 mos in the del17p group, 10.3 mos in the OHRC, and 10.3 mos in the standard-risk group (p = 0.92). The median OS was 15.5 mos for patients who received Seli as a bridging therapy versus 9 mos for Seli use for other reasons rather than as a bridge. Overall, Seli-based regimens showed promising responses even in this heavily pretreated population. Our analysis suggests that Seli-based regimens lead to similar outcomes among RRMM patients with del17p, OHRC, and standard-risk cytogenetics. This contrasts with previously reported outcomes using combinations of novel therapies in this population, where the del17p patients often have a poorer prognosis. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.

Introduction: Patients with multiple myeloma (MM) often report distress related to physical symptoms or psychological and social factors. Disease-related complications such as skeletal-related events, risk of renal compromise and anemia, as well as toxicities secondary to therapies over time are common in MM due to the chronic nature of the disease. About 80-90% of patients with MM have osseous lesions, which can lead to pain, fractures, and debility. NCCN and ASCO guidelines recommend early utilization of supportive care services (SCS) in all cancer patients for symptom control while being treated for their primary malignancy. Still, the underutilization of SCS in MM patients has been cited in current literature. We evaluated SCS utilization, level of distress, clinical characteristics, response to therapy, emergency department (ED) visits, and hospitalizations in patients with MM. Methods: We performed a retrospective analysis of adult patients with newly diagnosed or relapsed/refractory MM at Levine Cancer Institute who had completed an electronic distress survey (EDS) within three months of diagnosis or relapse. The EDS contained sociodemographic questions and patient-reported outcomes (PROs): distress level, physical symptoms (scale 0-10), screening for depression (PHQ-2, scale 0-6), screening for anxiety (GAD-2, scale 0-6), and daily function. Utilizations of SCS were identified from the electronic medical record (EMR) by visit types and provider names and included encounters within 6 months after completing the EDS. ED visits and hospitalizations were identified from the EMR within 1 year after EDS date. Categorical variables were summarized using frequencies and proportions, while numerical variables were summarized with descriptive statistics. The PROs were summarized overall and compared among three distress groups [distress score (DS) <4, 4-6, ≥7] with Wilcoxon rank sum tests for the EDS symptom scores and Fisher's exact tests for other categorical endpoints. Logistic regression was utilized to evaluate SCS utilization versus factors of interest. Results: We identified 148 patients with MM with an EDS assessment within the defined window (assessment date range 12/16/19 - 10/26/21). The mean age was 65.7 years. Of the patients, 64.2% were male; 77% were newly diagnosed with MM, while 23% of patients had relapsed/refractory disease. By self-identified race, 59.2% were White, 34.7% were Black, and 6.1% identified as other racial groups. For newly diagnosed MM, patients with high distress (DS ≥7) had higher rates of lytic bone disease compared to low distress (DS <4) (69.4% vs 50.9%, p = 0.17). In relapsed MM, a greater number of prior lines of treatment (4 vs. 3, p=0.08) and higher rates of prior stem cell transplant (77.8% vs. 61.5%, p = 0.46) were associated with higher distress scores. There was no association between DS and ISS, R-ISS stage, presence of high-risk cytogenetics, neuropathy, kidney disease, or heart failure at the time of the EDS. Patients with high distress scores reported more pain (p <0.001), fatigue (p <0.001), nausea (p = 0.047), sleep disturbances (p <0.001), diarrhea/constipation (p = 0.002), sexual concerns (p = 0.014), memory/concentration difficulties (p <0.001), anxiety (p <0.001), and depression (p <0.001). Rates of SCS utilization increased across the increasing DS groups (DS<4: 37.7%, DS 4-6: 69.6%, DS ≥7: 73.5%, p<0.001), and with the presence of lytic bone lesions (OR 3.73, p <0.001). On multivariable logistic regression, there was a significant association between DS and SCS utilization within 6 months after EDS, after adjusting for age and lytic bone lesions at initial assessment [OR (DS 4-6 vs <4): 4.17, OR (DS ≥7 vs <4): 4.26; p=0.001]. There was also no association between DS and subsequent ED visits, hospitalizations, or MM treatment response 6 months and 12 months after EDS. Conclusion: Certain clinical features of MM and common toxicities of MM treatments correlate strongly with distress in patients. At our cancer center, patients with higher DS resulted in a higher rate of SCS utilization, but higher DS scores were not associated with a higher rate of ED visits and hospitalizations. Further investigation is needed to evaluate whether the higher rate of outpatient SCS utilization for patients with higher levels of distress leads to a reduced rate of hospitalization and ED visits compared to patients with lower distress.

Background: Primary plasma cell leukemia (pPCL) represents the most aggressive plasma cell dyscrasia and has distinct biologic and clinical features which differentiate it from multiple myeloma. The International Myeloma Working Group (IMWG) adopted a more inclusive diagnostic criteria in 2021, but still pPCL remains rare and is nearly always an exclusion criterion for clinical trials. Classically, the prognosis of pPCL has been poor, with OS < 3 years. However, most published studies of pPCL represent small cohort and often don't include patients who meet criteria for pPCL based on the newer 2021 diagnostic guidelines. Given the limited data on appropriate treatment of pPCL we conducted a multi-center retrospective analysis of induction and consolidation regimens in pPCL patients with a goal of determining the optimum treatment for this condition. Methods: Patients with newly diagnosed pPCL based on the 2021 IMWG guidelines (i.e. ≥5% circulating plasma cells) diagnosed prior to 12/31/23 at either Levine Cancer Institute or University of Kansas Medical Center and who received at least 1 cycle of induction therapy were included. Using R Core Team (2024) software, a descriptive analysis was performed. Continuous variables were summarized and reported the mean (min, max) and median (IQR). Dichotomized factors were summarized by total numbers and frequency. Fisher's exact was used to analyze contingency tables. Wilcoxon rank-sum test is used to compare two independent samples. Responses to therapy were evaluated using the International Myeloma Working Group (IMWG) criteria. Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) calculations. A univariate/multivariate Cox proportional hazards analysis assessed the relationship between variables and a time-to-event outcome. The analysis calculates hazard ratios (HRs) and their associated confidence intervals (CIs) for each predictor variable, adjusting for censoring in survival data. Results: A total of 56 patients were identified and included in our analysis. Median age at diagnosis was 63 (33-81); 35 patients (63%) were female, and 14 (25%) were African American. The majority of patients (54%) had high risk cytogenetics [defined as presence of del 17p, amplification (≥4 copies) of 1q, t(4;14), t(14;16), t(14;20), or complex cytogenetics]. Median circulating plasma cells at diagnosis was 34% (5-82). Notably, 13 (23%) of included patients has 5-19% circulating plasma and would not have met the prior definition for pPCL. Most (48%) patients received infusional chemotherapy with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE) based induction regimens followed by cyclophosphamide, bortezomib, and dexamethasone (CyBorD- 25%) and lenalidomide, bortezomib, and dexamethasone (RVd-13%). Thirty-five (63%) patients underwent stem cell transplant. Of these, 20 had a single autologous transplant, and 15 underwent a tandem (7 auto-auto and 8 auto-allo). Overall response rate (ORR) was similar in patients after induction and transplant-in those patients who proceeded to transplant (75%; vs 80%), but depth of response (defined as a ≥VGPR) was significantly improved with transplant (53% vs 77%). Median OS was 22 months in the entire patient population; however, it was 9 months (95% CI 9; 27) in patients who did not proceed to transplant and was 46 month in patients who underwent any transplant (HR 0.30; 95% CI 0.16; 0.58). Median OS in patients who underwent any tandem transplant was 21 months, but was significantly improved for patients who had auto-auto tandem transplant (median OS 75 months; HR 0.05; 95% CI 0.0; 0.57). Conclusions: Primary plasma cell leukemia remains a rare but aggressive form of plasma cell dyscrasia with limited data to guide treatment. Our dataset represents the largest cohort to date using the expanded definition of pPCL adopted by the IMWG in 2021. Our analysis shows that stem cell transplant significantly improves OS and that double autologous tandem transplant provides additional survival benefit. As many patients diagnosed with pPCL are ineligible for transplant based on end-organ damage from uncontrolled disease or disease that is refractory to induction therapy, more efforts are needed to diagnose and treat pPCL to allow patients to proceed to transplant.

Introduction: CAR T-cell therapy has made a significant impact in the treatment of relapsed and refractory (R/R) DLBCL. However, there are significant barriers to timely administration of CAR T. Vein-to-vein time (time between leukapheresis and CAR T infusion) is an important barrier reported by clinical trials. In the real world, administration of CAR T may be further delayed due to financial clearance or single case agreement (SCA), shortage of leukapheresis slots, disease progression and death, among others. The time between CAR T referral and infusion (brain-to-vein) in the real-world is unknown. Understanding the barriers to timely administration of CAR T is crucial to expanding the access to CAR T for patients with R/R DLBCL. Methods: Adult patients (pts) with R/R DLBCL who underwent consultation for CAR T at our center from 2018 to 2022 were included in the study. The following information was collected from each subject and analyzed with descriptive statistics: referral type (internal/external), insurance type (private/government), private insurance subtype (SCA/non-SCA), and CAR T product (liso-cel/axi-cel/clinical trial/non-conforming product). For continuous variables, we reported the median and range, while categorical variables were reported as frequencies and percentages. The brain-to-vein time was classified as high (70-130 d), medium (45-70 d), and low (27-45 d). The effects of variables on brain-to-vein time were analyzed by Fisher's exact test for categorical variables, and Wilcoxon rank-sum test for continuous variables. Survival analyses were performed using the Kaplan-Meier and Cox Proportional Hazard model. Results: The study included 78 consecutive pts who were referred for consideration of CAR T for DLBCL. Thirteen (16.6%) pts did not receive CAR T therapy due to disease progression and death (n=5), lack of social support or caregiver (n=4), lack of financial clearance (n=2), and complete response to bridging therapy (n=2). Sixty-five (83.3%) pts received CAR T therapy. Median age was 61 y (27-83), 72% were male, and 18.4% belonged to racial or ethnic minority groups. The median time (range) from consultation to financial clearance, leukapheresis, and CAR T infusion were 15 (-50, 89), 30 (3, 91) and 61 d (27, 130), respectively. For some pts financial clearance was obtained prior to consultation. The median vein-to-vein time was 31 d (16, 76). There was no difference in brain-to-vein time (p=0.66) for external and internal referrals. Although pts with private insurance took longer to obtain financial clearance compared to pts with government insurance (median, 20 vs 9 d, p=0.01) (Table 1), there was no significant difference in the brain-to-vein time between the 2 groups (p=0.24). 20% of pts with private insurance needed SCA. Compared to those who did not need SCA, pts who needed SCA had a significant delay in time from consultation to financial clearance (median, 30 vs 19 d, p=0.01) and CAR T infusion (median 79 vs 55 d, p<0.001) (Table 2). Brain-to-vein time was significantly different among different products, with clinical trial the shortest (47 d, n= 9), non-conforming products the longest (99 d, n=5), and axi-cel (57 d, n=40), liso-cel (75 d, n=11) in between (p<0.001; Table 3). Of the 5 pts who received non-conforming products, 4 were intended for liso-cel and 1 for axi-cel. Brain-to-vein time did not significantly impact the progression-free survival [hazard ratio (HR)=0.988, 95% confidence interval (CI) = 0.973-1.003, p=0.11) or overall survival (HR=0.990, 95%CI=0.972-1.009, p=0.30) (Table 4). There was concordance when the time from consultation to CAR T therapy was used as a continuous variable and when it was separated into low, medium, and high quartiles and tested as categorical variables (Tables 2-4). Conclusion: We have identified multiple factors that prolonged brain-to-vein time for CAR T-cell therapy in the real-world. Pts whose insurance required SCA or who received non-conforming products had significant delay in receiving CAR T. Although delay in receiving CAR T therapy did not impact survival at our institution, several patients who could have benefited from CAR T did not receive it due to disease progression/death (6.4%) or lack of financial clearance (2.6%). Rapid financial clearance and eliminating the need for SCA could abbreviate the brain-to-vein time and expand access to patients with rapidly progressive DLBCL.

Introduction. CAR T-cell therapy is potentially curative for patients with relapsed or refractory B-cell lymphoma (BCL). However, about 60% of patients fail CAR T-cell therapy. Immune-related adverse events (irAE) like cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) occur in an inflammatory state. Myeloid-derived suppressor cells (MDSCs) expand during acute inflammation as steady-state hematopoiesis switches to emergency myelopoiesis. We hypothesized that the acute inflammatory conditions created by CAR T-cell therapy may alter MDSC kinetics and investigated MDSC expansion in the context of CAR T-cell efficacy and toxicity in BCL. Methods. Patients with BCL receiving standard-of-care CAR T-cell therapy were enrolled in a prospective sample collection study. Blood samples were collected before lymphodepletion (baseline), prior to and at early intervals after CAR T-cell infusion. Viable white blood cell (WBC) and MDSC counts were evaluated by multicolor flow cytometry. Phenotypically, MDSCs were defined as immature myeloid cells (CD11b + CD33 + HLA-DR -/low IL-4R +) and divided into monocytic (M-MDSC, CD14 +) and polymorphonuclear (PMN-MDSC, CD15 +) subsets. Clinical response was assessed by Lugano criteria at 1, 3 and 6 months. Incidence and severity of CRS and ICANS were recorded. Cell counts were analyzed by descriptive statistics and reported as mean ± standard error or fold-change from baseline. Kinetics of MDSCs in blood and correlation with clinical outcomes were evaluated by Wilcoxon matched pair signed rank t-test and Mann Whitney U-test. Results. Forty-three BCL patients (41 large BCL, 2 mantle cell lymphoma) were enrolled in the study. Median age was 64 (range 27-83), 32.6% were female. Racial and ethnic minority groups represented 14% of enrolled subjects. One patient developed grade 5 ICANS and was not evaluable for response. Thirty-seven (86%) developed leukopenia and all received granulocyte colony stimulating factor (G-CSF) starting on day 5 post-CAR T infusion. WBC count fell sharply from baseline following lymphodepletion (7.7E +05±8.6E +04 baseline vs 2.9E +05±9.2E +04/mL, p<0.0001) and continued to decline 2-3 days post-CAR T infusion (baseline vs 1.4E +05±2.1E +04/mL, p<0.0001) before returning to baseline within 1 week post-CAR T (i.e. within 3 days of G-CSF). MDSCs followed similar kinetics early on but significantly increased from baseline levels by 1-week post-CAR T (3.4E +03±5.8E +02 baseline vs 8.5E +03±1.7E +02 /mL, p<0.0001). This effect was mainly driven by an exuberant expansion of M-MDSC observed in 33/43 patients (median 6.1-fold increase from baseline at 1 week, range 0.5-4301). Seven patients (16.3%) had progressive disease (PD) at 1 month, 6 (13.9%) additional patients progressed at 3 months and 4 (9.3%) more progressed at 6 months after CAR T-cell infusion. M-MDSC expansion 1-week post-CAR T was only observed in 3/7 refractory patients compared with 28/35 responding patients (Fisher's exact test, p=0.0635). Patients who progressed at 3 months had poorer M-MDSC retention compared to patients with sustained response (1.7E +02±6.1E +01 PD vs 1.4E +03±2.4E +01/mL at 2-week post-infusion, p<0.1). Similarly, patients who progressed at 6 months had lower M-MDSC compared with sustained responders (2.0E +02±8.1E +01 PD vs 4.5E +02±1.4E +02 ml at 1-month post-infusion, p<0.05). Thirteen patients (30.2%) developed > grade 2 CRS and had lower PMN-MDSC retention rate 2-3 days post-CAR-T compared with those with no/low-grade CRS (4.4E +02±2.6E +02 vs 1.4E +03±3.9E +02/mL, p<0.05). Similarly, patients who had ICANS > grade 2 (n=14, 32.5%) had lower PMN-MDSC early retention compared to those with no or low-grade ICANS (5.0E +02±2.5E +02 vs 1.5E +03±4.1E +02/mL, p<0.05). Further analyses are currently underway to bridge these findings with the kinetics of CAR T-cells and T-cell repertoire post-CAR T. Conclusions. The proinflammatory milieu after CAR-T and the use of G-CSF can lead to significant expansion of M-MDSCs. Rather than an impediment to CAR T therapy, M-MDSC expansion and retention are associated with favorable clinical response and PMN-MDSC with a lower risk of developing high grades CRS or ICANS. Whether MDSCs play a mechanistic role remains to be elucidated, but they may have a role as a biomarker in predicting outcomes after CAR T-cell therapy in BCL.

e16300 Background: EOPC is associated with significant life years lost. Approximately 5%-10% of pancreatic adenocarcinoma (PAC) have an underlying genetic predisposition and national guidelines recommend testing in all patients with PAC. Certain germline mutations such as BRCA2 and PALB2 predict response to specific treatments including platinum and targeted therapies. It is currently unknown to what extent patients with EOPC pursue recommended germline testing. We examined the utilization of germline testing in patients with EOPC who were referred to genetics. Methods: A retrospective review of patients with EOPC at the Levine Cancer Institute (LCI), defined as ≤60 years of age at time of diagnosis, who were referred and seen by genetics between January 2019 and December 2021 was performed. Germline testing was performed using multi-gene cancer panels. Positive germline testing was considered as any known pathogenic or likely pathogenic variant not including variants of unknown significance (VUS). Results: We identified 69 patients with EOPC who were evaluated by genetics. The median age was 55 years (range 25-60) with 36 (52%) male, 33 (48%) female, 48 (70%) white, 16 (23%) Black, 61 (89%) with ECOG 0-1, 36 (52%) current or prior smoking history, and 28 (42%) presenting with metastatic disease. As shown, out of 69 patients, 10 (14%) declined testing or had unknown results, 30 (43%) had negative germline testing, 29 (42%) had genetic testing that revealed 19 (65%) had VUS, and 10 (34%) had pathogenic variants. The most frequently seen pathogenic variants were ATM (30%), BRCA1 (30%), BRCA2 (10%), MLH1 (10%), RAD51C+ (10%) and CFTR (10%). Conclusions: Our data suggest that most patients with EOPC who are evaluated undertake germline testing. Given the predictive nature of certain pathogenic mutations on PAC treatment options, characteristics of patients with EOPC who decline testing should be further explored. There is need for larger studies to confirm the high incidence of pathogenic variants observed in our cohort of EOPC patients. [Table: see text][Table: see text]

Introduction: Multiple myeloma (MM) is the second most common hematological malignancy. Current literature represents substantial underutilization of guideline-recommended supportive services (SS) in MM patients. Earlier studies have shown that most patients with MM have focal osseous lesions leading to skeletal-related events, fractures, pain, and debility. These events may negatively affect the treatment course and result in poor quality of life. Recent NCCN and ASCO guidelines recommend utilization of SS in all patients by early integration of cancer care for symptom control while being treated for primary malignancy. We evaluated the level of distress in patients (pts), SS utilization, ED visits, and hospitalization in pts with MM. Methods: We included adult patients (≥18 years) with newly diagnosed or relapsed/refractory MM at Levine Cancer Institute who had completed an electronic distress survey (EDS) within three months of diagnosis or relapse. Amyloidosis and plasma cell leukemia diagnoses were excluded. The EDS includes questions related to sociodemographic, patient-reported outcomes (PROs): distress level, physical symptoms (scale 0 - 10), screening for depression (PHQ-2, scale 0 - 6), anxiety (GAD-2, scale 0 - 6),Utilization of at least one SS (social work, palliative medicine, psych-oncology, cancer rehab, integrative medicine, and nutrition) within 6 months of EDS and emergency department visits/hospitalizations within 1 year of EDS were collected, retrospectively, from the electronic medical record. The PROs were summarized overall and compared among three distress groups [Distress score (DS) <4, 4-6, ≥7] with Wilcoxon rank sum tests for the EDS symptom scores and Fisher's exact tests for other categorical endpoints. Results: 541 MM pts were identified with an EDS within 3 months of diagnosis or relapse (assessment date range: January 2017 - May 2022), with 71.5% of those occurring near diagnosis, and 28.5% occurring around relapse. The mean age was 64.9 years, 58.6% were male, and additional patient characteristics are presented in Table 1. There were 33.8% (n=183) pts with DS<4, 30.9% (167) with DS 4-6, and 35.3% (191) with DS of ≥7. The highest scoring EDS symptoms were pain (mean score 4.7), fatigue (5.1) and sleep disturbance (3.6). Broadly, patients with higher distress scores had higher symptom scores (p<0.05 for all symptoms). There were 77.6% (420) pts with anxiety GAD-2 score of 0-2, 12.9% (70) pts with a score of 3-4 and 9.4% (51) pts with a score of 5-6. Similarly, for depression, 76.9% (416) pts reported a PHQ-2 score of 0-2, 15% (81) with a score of 3-4, and 8.1% (44) with a score of 5-6. For anxiety and depression, patients with higher DS had higher depression and anxiety screening scores (p <0.001), as shown in Table 2. 64.3% (348) pts utilized at least one SS within six months of their initial EDS assessment. The rate of utilization of at least one SS increased with DS (49.2% in DS <4, 67.1% in DS 4-6, and 76.7% in DS ≥7; p value<0.001). Numerically, more patients with high distress had at least one ED visit within a year of EDS (25.7% DS <4, 33.5% DS 4-6, 36.1% DS ≥7, p = 0.08). There was no significant difference in hospitalization within 1 year between the DS groups. There were 147 (36.8%) pts with high-risk cytogenetics, of which 43.5% had a distress score of ≥7. The rate of utilization of SS, ED visits, and hospitalizations was numerically higher in pts with newly diagnosed MM (68.5%, 34.4%, 63.1%, respectively), as compared to pts with RRMM (64.3%, 25.3%, 48.7%). Conclusion: The disease-specific symptoms predict clinically significant DS >4 on EDS. There were about 20% of pts with screening score >2 for anxiety (GAD-2) & depression (PHQ-2) that may warrant further exploration regarding the detail and nature of symptoms related to the diagnosis. There was a higher rate of utilization of SS and ED visits in pts with higher DS. Given these findings, there is a need to identify the optimal healthcare pathways for better utilization & incorporation of these EDS and PROs in the clinical care of distressed patients. Our study indicates that more work is needed to align needs with resources in order to optimize quality of life and disease outcomes for our pts.

Adoptive cellular immunotherapy, mainly hematopoietic stem cell transplant and CAR-T cell therapy have revolutionized treatment of patients with acute leukemia. Indications and inclusion criteria for these treatments have expanded in recent years. While these therapies are associated with significant improvements in disease response and overall survival, patients may experience adverse events from associated chemotherapy conditioning, engraftment, cytokine storm, supportive medications, and post-transplant maintenance targeted therapies. Supportive oncodermatology is a growing specialty to manage cutaneous toxicities resulting from the anti-cancer therapies. In this review, we summarize diagnosis and management of the common cutaneous adverse events including drug eruptions, graft-versus-host disease, neoplastic and paraneoplastic complications in patients undergoing cellular therapies.

8048 Background: Coronavirus-2 has profound effects on patients (pts) with Multiple myeloma (MM). At the beginning of the pandemic, COVID-19 infection resulted an overall mortality around 54% (cook et al. BMJ 2020). Here, we report an updated morbidity and fatality for MM. Methods: After obtaining IRB approvals from each participating institute, retrospectively, between January 1, 2021 and August 30, 2021, we identified pts with MM and COVID-19 in two myeloma centers (Levine Cancer Institute (LCI) & the University of Kansas medical center (KUMC). Results: We identified 162 MM pts who had COVID-19 (LCI n=132, UKMC n=30), including 57% males, with median age of 64 years. Current or former smoking reported in 40% of pts. Most pts have associated comorbid conditions: hypertension (45%), hypogammaglobulinemia (32%), CKD (30%), DM (22%), obesity (16.6%), CHF (14%), and CAD (13.5%). Within 3 months prior to infection, treatment included immunomodulatory combinations in 35%, proteasome inhibitors in 28 %, and Daratumumab in 26.5%. Symptoms are summarized in table. 69% had Mild symptoms (no need for hospitalization), 20 % had moderate symptoms (requiring hospitalization), and 9.8% had severe symptoms (ICU level of care). The 18% of pts required oxygen: 6 pts required invasive oxygenation and 3 pts needed vasopressors. The 32% of pts had RRMM, 29.5% on maintenance, and 12% was getting induction. Regarding MM response: >VGPR in 45% and PD in 18%. The 78 pts had ASCT prior to COVID-19 infection: only 3 pts < 1 year and 3 pts < 6 months. MM response or ASCT did not affect hospitalization or mortality.The case fatality rate (CFR) was 6%. In the univariate analysis, CKD, DM, HTN and hepatic dysfunction were associated with an increased risk of hospitalization. However, in multivariate analysis, only CKD, hepatic dysfunction, and Hypogammaglobulinemia significantly increased the risk of admission with only age and lymphopenia were associated with increased COVID-19 related fatatlity. Conclusions: With implementation of center-specific disease control measures and universal screening, pts might have lower case severity and fatality rate than was initially reported. [Table: see text]

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disorder of the immune system. While familial HLH is usually seen in children, secondary HLH is more common in adults. Secondary HLH is associated with a wide variety of underlying conditions including infections, malignancy and autoimmune disorders. While HLH 94/04 protocol-based chemotherapy can be used for initial treatment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment modality for this disorder. In this systematic review, we analyzed available literature on the role of allo-HSCT in adolescent and adult patients using PubMed, Cochrane, Embase and ClinicalTrials.gov. A total of 11 retrospective studies evaluated the role of allo-HSCT for HLH. Allo-HSCT, when compared to non-HSCT approach, appears to be associated with reasonable efficacy and acceptable safety for adolescent and adult patients with HLH.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

Background Recently published randomized controlled trials (RCTs) showed improved overall survival (OS) and progression-free survival (PFS) with the combination of immunotherapy and chemotherapy as compared to chemotherapy alone in advanced non-small cell lung cancer (NSCLC). We aimed to provide a systematic review and meta-analysis of RCTs regarding the efficacy and safety of immunotherapy and chemotherapy combinations for advanced NSCLC. Methods On December 23(rd), 2021, we searched databases for RCTs that reported PFS and OS as primary outcomes. Results We included 11 RCTs with 6,386 patients (3,850 in the combination therapy group and 2,536 in the chemotherapy group). Combination therapy was associated with an improvement in PFS (HR: 0.60; 95% CI: 0.54, 0.66; P < 0.00001) andOS (HR: 0.77; 95% CI: 0.68, 0.87; P <= 0.0001), compared to chemotherapy. There were no significant differences between both groups in terms of treatment-related adverse events (TRAEs) (RR: 1.07; 95% CI: 0.99, 1.16; P = 0.09). Conclusion The combination of immunotherapy and chemotherapy as first-line treatment for advanced NSCLC significantly improved PFS and OS compared to chemotherapy alone without a significant increase in the overall TRAEs.

Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering cell cycle arrest and the death of malignant cells. Multiple Myeloma (MM) patients with del17p are deficient in TP53 and have a particularly poor prognosis. Given its unique mechanism of action, we investigated whether Seli has increased efficacy in RRMM patients with del17p compared to other high-risk cytogenetics (OHRC). This is an IRB-approved observational study of RRMM patients with high-risk cytogenetics (del17p, t (4;14), t (14;16) or gain 1q) or standard-risk cytogenetics treated at the Levine Cancer Institute (LCI) with a Seli-based regimen between January 2019 and December 2022. Time-to-event endpoints (PFS, OS) were evaluated using Kaplan–Meier (KM) methods. Log-rank tests compared time-to-event endpoints between cohorts [del17p vs. OHRC vs. standard risk]. We identified 40 RRMM patients with high-risk cytogenetics, including 16 patients with del17p and 24 patients with OHRC, as well as 20 with standard-risk cytogenetics. The median age was 62.5 vs. 69 vs. 65.5 years (del17p group vs. OHRC vs. standard risk). The median prior line of therapies was five (range: 3–16) with similar rates of prior autologous stem cell transplant in all arms (68.8% vs. 62.5% vs. 70.0%). The most frequently used regimens were Seli–Pomalidomide–dexamethasone(dex) or Seli–Carfilzomib–dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. The median time to start the Seli-based regimen after initial MM diagnosis was 5.6 years for the del17p group, 4.1 years in OHRC, and 4.8 years in the standard-risk group. The median follow-up time after the start of the Seli-based regimen was 10.5 months (mos) in the del17p group, 8.4 mos in OHRC, and 10.3 mos in the standard-risk group. In the del17p group, 50% had an objective response, 41.7% in the OHRC, and 35% in the standard-risk group (p = 0.71). Depth of response was also similar across the arms (12.5% vs. 12.5% vs. 10.0% VGPR p = 0.99). The median OS was 10.9 mos in the del17p group, 10.3 mos in the OHRC, and 10.3 mos in the standard-risk group (p = 0.92). The median OS was 15.5 mos for patients who received Seli as a bridging therapy versus 9 mos for Seli use for other reasons rather than as a bridge. Overall, Seli-based regimens showed promising responses even in this heavily pretreated population. Our analysis suggests that Seli-based regimens lead to similar outcomes among RRMM patients with del17p, OHRC, and standard-risk cytogenetics. This contrasts with previously reported outcomes using combinations of novel therapies in this population, where the del17p patients often have a poorer prognosis. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.

Medical uninsurance (MU) is associated with cancer disparities, particularly among underprivileged and minority sections of the United States. In this cross-sectional study of National Health and Nutritional Examination Survey (NHANES) data from 2013 to 2018, we evaluated sociodemographic attributes of MU disparity in the US cancer population. Those aged >= 20 years with a history of cancer and disclosed MU status were included. We calculated the descriptive statistics of the population stratified by insurance type and performed bivariate and multivariate logistic regression models to assess the association of sociodemographic attributes and MU and reported unadjusted (UOR) and adjusted odds ratios (AOR). Among the 1681 participants (US estimated, 25,982,352), 4.3% +/- 0.62 were uninsured. Uninsured individuals were 13.5-year younger, largely female, less educated, and non-US born compared to insured individuals. Age (UOR: 0.94, 95% CI: 0.93-0.96), female sex (UOR: 3.53, 95% CI: 1.73-7.19), Hispanics (UOR: 4.30, 95% CI: 2.45-7.54), <high school education (UOR: 7.41, 95% CI: 2.51-21.86), and non-US born with <20-years-stay in US (UOR: 7.69, 95% CI: 3.32-17.82) were associated with MU. In the multivariate model, age (AOR: 0.95, 95% CI: 0.93-0.96), female sex (AOR: 2.88, 95% CI: 1.25-6.62), <high school education (AOR: 4.02, 95% CI: 1.24-13.00), and non-US-born status with <20-years stay (AOR: 3.42, 95% CI: 1.44-8.11) were independent predictors of MU. Income was not a predictor of MU. The US cancer population has unique determinants of MU. Ethnicity alone is not a predictor of MU, whereas income is not correlated with MU. Public health interventions focusing on the attributes of MU are needed.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by clonal expansion of myeloid blasts. It is the most common type of acute leukemia in adults, including elderly patients, and has historically been associated with poor outcomes in this age group. Here, we present the case of an 80-year-old woman with newly diagnosed AML with myelodysplasia-related changes. She was treated with a total of five cycles of azacitidine, two cycles as monotherapy followed by three cycles in combination with venetoclax. Therapy was stopped due to cytopenias and declining performance status. Bone marrow aspirate and biopsy immediately following treatment and again approximately four months later did not show any morphologic, immunophenotypic, or cytogenetic evidence of leukemia. The patient's clinical and performance status improved significantly with time. Follow-up labs more than three years following the completion of treatment reveal continued hematologic remission. A short treatment course of azacitidine and venetoclax with close monitoring may lead to durable responses in some patients. Further studies are necessary to determine which patients might be appropriate for treatment suspension or discontinuation while in remission.

With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs. Selinexor in combination with dexamethasone has emerged as a viable option for heavily pretreated triple-class relapsed and refractory multiple myeloma (RRMM). In this systematic review, we analyzed available literature on the role of selinexor in RRMM. The Boston trial demonstrated that selinexor when combined with dexamethasone and bortezomib is associated with a better depth and duration of response without excessive toxicity, compared with bortezomib and dexamethasone alone. Similarly, selinexor in combination with carfilzomib and dexamethasone was found to have a durable response and tolerable safety profile in both carfilzomib-naive and carfilzomib refractory RRMM patients. Selinexor in combination with IMiDs (lenalidomide and pomalidomide) as well as CD38 monoclonal antibodies (daratumumab) also have promising results. Selinexor combination therapy is both safe and effective for patients with pretreated RRMM.

e16231 Background: Pancreatic cancer is the 11th most common cancer and represents 3.2% of all new cancer cases. But it is the third leading cause of cancer-related deaths with a five-year relative survival of only 10.8%. More than 50% of patients diagnosed with metastatic disease at initial presentation have 5-year relative survival of only 3.0%. Here, we explore the recent literature for the emerging role of immunotherapies and their outcomes for advanced pancreatic cancer. Methods: The literature search was conducted on PubMed, Embase, Cochrane, and ClinicalTrials.gov from inception to January 2022 using MeSH terms' pancreatic neoplasms', 'immunotherapy,' and 'therapeutics'. The final analysis includes nine clinical trials that meet the inclusion criteria regarding immunotherapy for metastatic pancreatic cancer. Results: The combination of pembrolizumab and trametinib with stereotactic radiotherapy (SBRT) reported a median progression-free survival (PFS) and overall survival (OS) of 25 and 18 months compared to gemcitabine and SBRT combination of 22 and 16 months, respectively. Another study reported a median OS of 18 months with nivolumab along with operative irreversible electroporation to increase the bioavailability of nivolumab in the cancer cells. The EGFR targeted CAR T cells therapy was evaluated in 14 patients with advanced pancreatic cancer with a median OS of five months and an overall response rate (ORR) of 29%. Sotigalimab, an agonistic CD40 antibody combined with nivolumab, was found to have an ORR of 58%, PFS of 12 months, and OS of 20 months after a follow-up of almost 18 months. On the contrary, Bruton's tyrosine kinase inhibitors such as Acalabrutinib and Ibrutinib were found to have no OS benefit (median OS 3.8 and 5.3 months, respectively). Conclusions: Due to the high mortality associated with advanced pancreatic cancer, there is increasing interest in Novel immunotherapies-based approaches, with some showing promising results.[Table: see text]