Langlais, Blake

e19008 Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.

Background: Bystander cardiopulmonary resuscitation (BCPR) significantly improves survival from out-of-hospital cardiac arrest (OHCA). Telecommunicator CPR (TCPR) has been shown to increase BCPR rates, yet TCPR performance varies widely. We assess whether a bundled TCPR protocol, training, and continuous quality improvement (CQI) intervention improves TCPR performance. Methods: The intervention was implemented at a regional 9-1-1 dispatch center and had three main components: (1) the installation of the AHA-recommended 2-question TCPR protocol, (2) training to enhance telecommunicator OHCA recognition and (3) CQI with system and case-level feedback. Training included a two-hour lecture, 30 minutes of video training, and one hour of simulation training. Audio recordings of suspected OHCAs from pre (P1, 10/5/10 - 11/6/11) and post-intervention (P2, 11/7/11 - 11/4/13) periods were collected by searching center archives for calls originally processed as cardiac arrests. Recordings were analyzed according to six key TCPR metrics. Times to telecommunicator recognition of cardiac arrest, start of TCPR instructions, and initiation of chest compressions were measured using a standardized timestamp format. Results: Rates of OHCA recognition (80% to 95%, p<0.0001), TCPR instructions started (32% to 72%, p<0.0001), and bystander chest compressions initiated (18% to 70%, p<0.001) all increased significantly. Reductions in the time from call receipt to the start of TCPR instructions (176s to 133s, p<0.0001) and to the start of compressions (265s to 162s, p<0.0001) were also observed. Conclusion: This bundled protocol, training and CQI intervention was associated with a significant increase in TCPR rates and a reduction in the time to first chest compression.

Background: Bystander CPR (BCPR) and telephone CPR (TCPR) are associated with improved OHCA outcomes. It has been shown that BCPR increases the proportion of patients with an initial shockable cardiac rhythm (VF/VT) when encountered by EMS. It is unknown whether TCPR does the same. Objective: To assess whether TCPR is independently associated with an increase in initial shockable cardiac rhythms during OHCA. Methods: Data from 9-1-1 audio recordings, first care EMS reports and hospital records were linked for OHCAs of presumed cardiac origin (1/2011-12/2014). Three cohorts were analyzed: TCPR, BCPR or no CPR. Using no CPR as the reference group, we assessed whether TCPR and BCPR were independently associated with initial shockable rhythms in a logistic regression model controlling for gender, event location, witness status and EMS response interval. Results: After exclusions, 2715 adult OHCA events with linked outcome data were analyzed (median age: 63; male: 66.8%; 33.3% witnessed arrest). Median response interval was 5 min. The BCPR rate (lay rescuer CPR without telephone instructions) was 24.8% and survival in this group was 15.4%. The TCPR rate (lay rescuer CPR with telephone instructions) was 40.2% and survival in this group was 11.7%. For the no-CPR group, 20.5% had an initial shockable rhythm. For the BCPR group, 34.6 % had an initial shockable rhythm. For the TCPR group, 23.2% had an initial shockable rhythm. Provision of BCPR and of TCPR were each independently associated with shockable rhythms [aOR (BCPR) = 1.7, 95% CI: 1.33-2.17, p=0.0001; aOR (TCPR) = 1.3, 95% CI: 1.04-1.63, p=0.0001]. Conclusion: The provision of both BCPR and TCPR were independently associated with an increased rate of initial shockable cardiac rhythms and an increase in survival to hospital discharge compared to no CPR.

Background. With increasing life expectancy, patients with HIV are more commonly acquiring other chronic diseases, such as end-stage lung disease, for which transplant may be the only effective solution. Until recently, HIV infection was considered a contraindication to lung transplant (LTx). As LTx in people living with HIV (PLWH) becomes more common, there remain limited data on outcomes in this population. Methods. Using the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, we identified LTx recipients with HIV by either serostatus or nucleic acid testing. A control group of confirmed HIV-negative LTx recipients was propensity score matched on age, body mass index, primary diagnosis, and year of transplant. Patient characteristics, transplant parameters, survival, and postoperative outcomes were compared. Results. Fifty-nine LTx recipients with HIV were identified and compared with 236 HIV-negative controls. Among PLWH, cytomegalovirus status was more frequently positive (76.3% versus 58.9%, P = 0.014), and the median Lung Allocation Score at match was higher (44 versus 39, P = 0.004). PLWH were more likely to undergo dialysis postoperatively (18.6% versus 8.9%, P = 0.033), although other complication rates were similar. Fifty-three percent of LTx for PLWH occurred since 2020. One-year survival for PLWH was 91.2% versus 88.6% for controls (P = 0.620). Three-year survival for a smaller subset was also not statistically significant (HIV versus control: 82.6% versus 77.8%, respectively, P = 0.687). Conclusions. There was no difference in 1-y survival for LTx recipients living with HIV compared with a matched control group, supporting this group of patients as viable candidates for LTx.

Abstract Background Immune checkpoint inhibitor combined with platinum‐etoposide is the standard first‐line therapy for patients with extensive‐stage small cell lung cancer (ES‐SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES‐SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2–3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2–3 are limited. Methods A retrospective analysis was performed on patients diagnosed with ES‐SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression‐free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0–1 vs. patients with an ECOG PS of 2–3 who received chemoimmunotherapy for newly diagnosed ES‐SCLC. Results In total, 82 patients were included in the study. The mean ± standard deviation age was 68.1 ± 8.3 years. Of these, 56 patients were identified with an ECOG PS of 0–1, and 26 patients were identified with an ECOG PS of 2–3. The median PFS was similar regardless of ECOG PS (5.8 months [95% CI, 4.3–6.0 months] in the ECOG PS 0–1 group vs. 4.1 months [95% CI, 3.8–6.9 months] in the ECOG PS 2–3; p = .2994). The median OS was also similar regardless of ECOG PS (10.6 months [95% CI, 8.4–13.4 months] in the ECOG PS 0–1 group vs. 9.3 months [95% CI, 4.9–12.8 months]; p = .2718) in the ECOG PS 2‐3 group. Conclusions The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2–3 and ECOG PS 0–1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES‐SCLC with an ECOG PS of 2–3.

e19078 Background: Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), experience chronic disease-related symptoms. Surveying these patients while incorporating the MPN-Symptom Assessment Form (SAF) gains valuable insight. Independent surveys evaluating symptoms among MPN patients have seen disproportionate participation among females compared to males (upwards of 4:1). Though the general MPN patient population is roughly gender balanced, epidemiological studies show the occurrence of MPN types differ between men and women (MPN [%male]: PV [65%], ET [33%], MF [50%]. Mehta, et al. Leuk & Lymph 2014). In-clinic evaluations and international MPN surveys of disease-related symptoms suggest women report higher symptom burden on average compared to men, despite MPN type [Emanuel, et al. JCO 2012. Geyer, et al. Haematol 2017]. Further, a recent study across cancer trials showed women had a 34% increased risk of reporting severe symptoms [Unger, et al. JCO 2022]. This study aimed to evaluate gender imbalance in survey participation among MPN patient surveys and investigate its potential to overestimate symptom burden if gender is ignored. Methods: Five anonymous web-based surveys were used to assess the impact of disproportionate gender participation. The MPN-10 assessing the 10 most clinically meaningful SAF items was present in these surveys and generated the Total Symptom Score (TSS). Survey responses with no self-reported gender or ≥5 missing MPN-10 symptoms were excluded. Raking weights based on expected MPN population were applied at the survey- and MPN type-level. Relative bias of mean TSS was calculated to evaluate over- and underestimation due to this participation imbalance. Relative bias <5% is commonly acceptable. Results: There were 4962 survey participants total and 74% were female (Table). Epidemiologically expected gender frequency by MPN type was not seen (MPN [%male]: PV [31%], ET [15%], MF [37%]). The gender participation imbalance accounted for a 3.1% overestimation of overall TSS. This also resulted in a 6.8% underestimation of the mean difference in TSS between genders, across MPNs. Conclusions: Overall bias due to gender participation imbalance was relatively low. However, analyses considering gender differences were more impacted. Anonymous surveys should seek to reduce participation bias during the survey design phase. More research is needed to evaluate gender and other participation biases in surveys across cancer domains.[Table: see text]