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OBJECTIVE Diabetes mellitus (DM) is a known risk factor for postsurgical and systemic complications after lumbar spinal surgery. Smaller studies have also demonstrated diminished improvements in patient-reported outcomes (PROs), with increased reoperation and readmission rates after lumbar surgery in patients with DM. The authors aimed to examine longer-term PROs in patients with DM undergoing lumbar decompression and/or arthrodesis for degenerative pathology. METHODS The Quality Outcomes Database was queried for patients undergoing elective lumbar decompression and/or arthrodesis for degenerative pathology. Patients were grouped into DM and non-DM groups and optimally matched in a 1:1 ratio on 31 baseline variables, including the number of operated levels. Outcomes of interest were readmissions and reoperations at 30 and 90 days after surgery in addition to improvements in Oswestry Disability Index, back pain, and leg pain scores and quality-adjusted life-years at 90 days after surgery. RESULTS The matched decompression cohort comprised 7836 patients (3236 [41.3] females) with a mean age of 63.5 ± 12.6 years, and the matched arthrodesis cohort comprised 7336 patients (3907 [53.3%] females) with a mean age of 64.8 ± 10.3 years. In patients undergoing lumbar decompression, no significant differences in nonroutine discharge, length of stay (LOS), readmissions, reoperations, and PROs were observed. In patients undergoing lumbar arthrodesis, nonroutine discharge (15.7% vs 13.4%, p < 0.01), LOS (3.2 ± 2.0 vs 3.0 ± 3.5 days, p < 0.01), 30-day (6.5% vs 4.4%, p < 0.01) and 90-day (9.1% vs 7.0%, p < 0.01) readmission rates, and the 90-day reoperation rate (4.3% vs 3.2%, p = 0.01) were all significantly higher in the DM group. For DM patients undergoing lumbar arthrodesis, subgroup analyses demonstrated a significantly higher risk of poor surgical outcomes with the open approach. CONCLUSIONS Patients with and without DM undergoing lumbar spinal decompression alone have comparable readmission and reoperation rates, while those undergoing arthrodesis procedures have a higher risk of poor surgical outcomes up to 90 days after surgery. Surgeons should target optimal DM control preoperatively, particularly for patients undergoing elective lumbar arthrodesis.

Background: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that carries lasting risks. For women who have a history of GDM, the risk of developing type 2 diabetes mellitus (T2DM) increases by 50 to 60%. To monitor and prevent the development of T2DM, guidelines suggest screening those with a history of GDM at 6-weeks and 3-years post-delivery. For patients with abnormal lab results at the 6-week mark, it is advised to complete lab work sooner, at the 1-year mark. Data suggests that these guidelines are not being followed globally, and most do not receive adequate screening for T2DM. Methods: A retroactive chart review of 203 women between 18 and 55 years old with a past medical history significant for GDM was conducted to determine if patients with GDM completed screening for T2DM at 6-week, 1-year, and 3-year timestamps post-delivery. Patient demographics (age, race, ethnicity, language), clinical characteristics (body mass index), provider gender, and whether prediabetes or T2DM developed were recorded. Patients who did not complete the required follow-up received educational materials via the online portal system, and hemoglobin A1c (HbA1c) screening tests were ordered. Results: Ninety days post-intervention, 38 patients (50%) completed the HbA1c screening test, which exceeded our goal of a 5% improvement. Age and BMI 1-year postpartum were found to be significant factors in whether a patient completed HbA1c screening, with 16/18 (89%) completing screening with a healthy BMI 1-year postpartum (18.5 ≤ BMI < 25.0) but only 11/41 (27%) completing screening for patients under 40 years with an unhealthy BMI 1-year postpartum. Of the 38 patients who completed HbA1c screening, 9 (23.7%) had abnormal screening results. Conclusion: Follow-up surveillance for T2DM among women with a history of GDM is poor. Electronic health records can be used to identify and rectify gaps in care. Dissemination of standardized educational materials and electronic order entry for patients improved screening between the handoff from obstetrics to primary care.

Abstract Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Background: GLUT4 inhibition via the use of a protease inhibitor, such as nelfinavir (NEL), is an attractive therapeutic option in multiple myeloma (MM), given the dependence of MM cells on glucose. Furthermore, combining a GLUT4 inhibitor with an oxidative phosphorylation inhibitor, such as metformin (MET), may counter the possibility of therapeutic resistance to GLUT4 inhibition in MM cells, showing synergistic promise (Dalva-Aydemir et al., Clin Can Res 2015). In addition to GLUT4 inhibition, NEL also lowers the cytotoxicity resistance of MM cells against proteasome inhibitors such as bortezomib (BOR) (Driessen et al., Blood 2018). Thus, this study evaluated the safety and tolerability of repurposing MET and NEL, in combination with BOR for the treatment of relapsed/refractory MM (RRMM) that had progressed on all standard of care (SOC) therapies. Methods: This trial utilized a 3+3 dose escalation design with 3 dose levels planned for up to a maximum of six (21-day) cycles. MET was administered for 14/21 days and started at a dose of 500 mg BID with plans to be investigated at a maximum dose of 1000 mg BID. NEL was administered for 14/21 days and started at a dose of 1250 mg BID with plans to be investigated to a maximum dose of 2500 mg BID. SubQ BOR was administered on days 1, 8, and 15 of a 21-day cycle at a dose of 1.3 mg/m 2 to a portion of patients. Patients with RRMM were required to have had 2 prior lines of therapy and prior exposure to proteasome inhibitors (PIs), immunomodulators (IMiDs), and Anti-CD38 monoclonal antibodies. The primary objective was to determine the maximal tolerated dose (MTD) of this combination. The secondary objective was to evaluate the safety as well as the overall response rate (ORR) of this combination. This trial was funded by the Helen Diller Family Foundation. Results: From 4/2019 until 9/2022, nine patients were accrued with a median age of 65 (range: 42-81) that received a median of 7 prior lines of therapy (Range: 6-13). All but one patient had a prior autologous stem cell transplant. Only one patient was not triple-class refractory, and 2/3 rd (n = 6) also had prior anti-BCMA therapy. The first three patients received only MET (500 mg BID) and NEL (1250 mg BID) at the first dose level for up to one cycle before experiencing progressive disease and coming off the study. Given the limited activity of MET and NEL in the initial treatment of these three patients, two subsequent amendments to the protocol allowed for the upfront addition of BOR 1.3 mg/m2 to the original combination, as well as shortened the DLT evaluation period from two cycles to just one. Thus, the following six patients received MET (500 mg BID) and NEL (1250 mg BID) at the first dose level in addition to weekly BOR at 1.3 mg/m2. Four (44%) patients experienced grade 3+ hematological AEs and six (67%) experienced grade 3+ non-hematological AEs. The most common hematologic grade 3+ AE observed was anemia (44%). The nonhematologic grade 3+ AEs observed were dyspnea, fatigue, nausea, and vomiting (11% each). None of the AEs were possibly related to treatment, suggesting good overall safety of the combination. While eight of nine patients have since died of progressive disease, no deaths were attributable to the treatment. All six patients who received BOR upfront with MET and NEL were previously refractory to BOR in prior lines of therapy; however, none had received BOR as their last line of therapy prior to accrual to this study. Four of these six patients had progressive disease after one cycle of therapy and went off study. However, the remaining two were able to receive 2 or more cycles of therapy, with one experiencing an unconfirmed minor response (MR) in the first cycle and the other experiencing stable disease (SD) for all six cycles. The patient who experienced SD was safely able to transition to a subsequent clinical trial utilizing an anti-BCMA bispecific antibody therapy and remains alive at the time of this analysis. The study was closed before accrual to the next dose level was started. Conclusions: This is the first study to evaluate the safety and efficacy of this repurposed drug combination in this very difficult-to-treat population of RRMM. While no ORR was observed, identification of biomarkers used for selection of patients with no other SOC options who could experience at least SD responses may be beneficial in allowing this combination to slow or stabilize the disease progression until other novel therapies or clinical trials are available.

Background: First-line therapies for chronic-phase (CP) CML include the tyrosine kinase inhibitors(TKIs) dasatinib, nilotinib, bosutinib or imatinib, while ponatinib and asciminib are indicated only in later lines. There are typically high response rates to first-line therapy in CP-CML, with responses to second- and third-line therapy lower and highly dependent on the specific TKI. Our goal in this study is to evaluate the role of ponatinib in the treatment of patients with CML using data from routine clinical practice. Study design and methods: Data will come from the H. Jean Khoury Cure CML Consortium (HJKC3) CML registry, a North American multi-site research database. Participating sites include the HJKC3 members (curecml.org). Patient inclusion criteria include a diagnosis CML in chronic phase, receiving second line therapy after initial therapy with a second generation TKI (dasatinib, nilotinib, or bosutinib) or receiving third or later line TKI therapy for CML. Participating patients provide consent to collect their data both retrospectively and prospectively for 1 year. Clinical data, including toxicities and complications of TKI therapy, are abstracted from the electronic health record. Participating patients are invited to complete a questionnaire to assess health-related quality of life. Data are managed using REDCap, a secure web application. Study Objectives: The primary objective is to compare the outcome of patients treated with ponatinib vs. other TKIs as second or later line therapy. Secondary objectives are to evaluate patient-reported outcomes (PRO) for CML treated with second or later line therapy and to determine if there are any patient or disease characteristics that can predict outcomes. Statistical plan for clinical outcomes: Descriptive statistics will be used to compare baseline demographic characteristics. Categorical variables will be compared using the Chi-square test. Continuous variables will be compared using ANOVA. Overall survival will be calculated from the time of diagnosis to death from any cause and patients will be censored if they were alive at the last follow-up. Survival probabilities will be computed using the Kaplan-Meier method and compared with the log-ranktest. Cox regression analyses will be used to determine significant factors that influence survival, and hazard ratios with 95% confidence intervals will be presented. Event free survival (EFS) and transformation free survival (TFS) will be calculated for patients. For EFS, loss of complete hematologic remission, loss of major cytogenetic response, progression to accelerated or blast phase, or death from any cause at any time will be considered an event. For TFS, transformation to accelerated or blast phase while on therapy or death on study will be considered an event. Statistical plan for PRO: Different PRO domains will be analyzed separately (for example, depression separate from fatigue, etc.). Descriptive statistics for each PRO measure will be reported and compared to previously published studies. Differences by treatment type will be evaluated.

Introduction The discovery of MAPK/ERK pathway mutations has revolutionized the care for patients with histiocytic neoplasms. However, mutational analysis on biopsy specimens is often limited by low tumor cellularity leading to testing failure or disease involvement of difficult-to-reach sites (e.g., central nervous system). Recently, molecular analysis of cell-free DNA (cfDNA) has shown promise as a viable tool for discovering driver mutations in multiple cancers. A recent study of mainly BRAF-mutated non-Langerhans cell histiocytosis (LCH) showed 50% concordance between tumor and plasma cfDNA analysis for BRAF-V600E. However, it is unknown whether cfDNA has a role in the evaluation of cases that harbor mutations beyond BRAF-V600E. We conducted this study to address this unanswered question using a large cohort of individuals with diverse histiocytic neoplasms from a tertiary-care institution. Methods We included 40 cases with histiocytic neoplasms with stored plasma and germline DNA in this study. Tissue molecular analysis was conducted using a targeted next generation sequencing (NGS) using commercial assays or whole exome sequencing (WES) using an in-house assay. A custom panel of 226 genes, including exonic and intronic regions, was used for the cfDNA assay in this study. To avoid cfDNA false positives, germline mutations identified from normal DNA sequencing were filtered using a BostonGene ®-developed error reduction algorithm.The total length of the analyzed genomic regions was 1.56 MB. For samples with an input greater than 30 ng, a 0.2% variant allele frequency (VAF) limit of detection (LOD) was used; a 0.4% VAF LOD was used for samples less than 30 ng. Results The final analysis cohort included 38 patients with histiocytic neoplasms after exclusion of 2 cases (failure of germline DNA library preparation and mismatch of germline and somatic DNA, respectively). Disease types included Erdheim-Chester disease (ECD; n=13, 34%), Langerhans cell histiocytosis (LCH; n=13, 34%), and Rosai-Dorfman disease (RDD; n=12, 32%). 24 cases were multisystem (63%), and the remaining were single-system. Commonly involved organs included bone (n=25, 66%), kidney (n=12, 32%), skin (n=8, 21%), central nervous system (n=7, 18%), and pituitary (n=7, 18%). Most cases (n=31, 82%) underwent plasma collection pre-treatment, 5 cases underwent collection after histiocytosis-directed therapy, and 2 while on treatment. Tissue NGS/WES data were available for 28 (74%) cases; 5 cases (13%) had insufficient tissue cellularity, and 5 (13%) did not undergo any tissue sequencing. Among those who underwent successful tissue sequencing assays, the most common common driver alterations was BRAF V600E (n=5, 26%). Other alterations included those in MAP2K1 (n=4, 21%), BRAF-fusions (n=3, 10%; partners UBDT2, RNF11, and LMTK2, respectively), and single cases of KRAS, NRAS and BRAF indel, respectively. cfDNA analysis showed at least one variant in 23 cases (60%). Correlation between tissue and cfDNA for known driver mutations was poor and concordant findings were only seen in one case with ECD harboring BRAF V600E in tissue as well as plasma (VAF 0.5%). Among the 5 cases where tissue mutational analysis had failed, cfDNA showed mutations in MUTYH, PTCH2, NOTCH3 SDHD, and TMEM127, respectively (Figure 1). Among the 5 cases where tissue molecular assessment could not be undertaken due to various reasons, cfDNA showed alterations in 4 cases, encompassing NOTCH1, TET2, BRCA1, MSH6, PIK3CD, and FUS genes. Conclusions In a large cohort of adults with diverse histiocytic neoplasms, we found poor correlation between tumor and plasma cfDNA molecular findings. The reason for the lack of correlation may be related to low tumor shedding especially among non- BRAF V600E cases. cfDNA analysis may have a role to identify potential drivers of pathogenesis among cases that are unable to successfully undergo tissue molecular analysis. Further studies are underway to characterize other novel alterations that were discovered in the cfDNA analysis.

Introduction ABBV-383 is a fully human, silenced Fc region IgG4 monoclonal, BCMA × CD3 T-cell-engaging bispecific antibody with 2 BCMA-binding domains and a low-affinity CD3-binding domain. ABBV-383 has shown promising activity following intravenous (IV) infusion every three weeks (Q3W) as monotherapy in patients (pts) with RRMM in an ongoing phase 1 study (D'Souza A, et al. J Clin Oncol. 2022 Nov 1;40(31):3576-3586; Voorhees et al. Blood 2022;140[suppl 1]:4401). Herein, preliminary pharmacokinetic (PK) and immunogenicity results from Q3W regimens of this study and impact of soluble BCMA (sBCMA) on ABBV-383 PK are reported. Methods In the phase 1 study (NCT03933735), adult pts with RRMM, who were previously exposed to ≥3 prior multiple myeloma agents including ≥1 proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody, received Q3W IV infusion at doses 0.025 - 120 mg in escalation (ESC) phase, and at 20 mg, 40 mg, and 60 mg in expansion (EXP) phase. Serial blood samples for PK characterization were collected in cycles 1, 3, and 6 along with sparse/periodic samples throughout the study. Blood samples were also collected throughout the study to detect anti-drug antibodies (ADAs) for immunogenicity characterization and to determine sBCMA concentrations. Appropriate validated assays were used to determine ‘total’ (unbound and bound to sBCMA) and ‘free’ (unbound and partially bound to sBCMA) ABBV-383 serum concentrations, to detect/determine ADAs/titers, and to determine total sBCMA concentrations. ‘Total’ and ‘free’ ABBV-383 serum concentrations from cycles 1, 3, and 6 were used to calculate individual PK parameters (peak concentration [C max], trough concentration [C trough], area under the concentration-time curve [AUC], terminal phase elimination half-life [t 1/2], clearance [CL], and steady state volume of distribution [V ss]) using non-compartmental analysis in Phoenix WinNonlin Version 8.2. Immunogenicity was summarized using ADA/titer data. Impact of baseline/pre-dose sBCMA concentrations on ‘total’ and ‘free’ ABBV-383 PK parameters from cycles 1, 3, and 6 was explored. Results ‘Total’ and ‘free’ ABBV-383 intensive PK data (cycles 1, 3, and 6) were available from 169 and 157 pts, respectively, representing Q3W regimens in ESC and EXP cohorts and ADA data were available from 186 evaluable subjects. Preliminary PK results suggest that ‘total’ and ‘free’ ABBV-383 exhibited approximately dose-proportional PK between 5.4-120 mg Q3W. Estimated t 1/2 for ‘total’ and ‘free’ ABBV-383 ranged between 11-12 days and 8-11 days, respectively, with steady state achieved by cycle 4 in Q3W EXP cohorts. Estimated CL and V ss were consistent with those of a typical IgG4 antibody in humans. Across EXP Q3W regimens, accumulation (cycle 3 vs. cycle 1) was 30%-60% in C max and 60%-177% in C trough for ‘free’ and ‘total’ ABBV-383. ABBV-383 exposures (AUC tau and C trough) of ‘total’ ABBV-383 were 28-74% higher than those representing ‘free’ ABBV-383 among the EXP Q3W regimens with no/minimal observed differences in C max (≤21%). Higher sBCMA levels prior to treatment appeared to reduce ‘free’ ABBV-383 PK exposures with pronounced reduction at lower doses (e.g., 20 mg) and in cycle 1, however the effect diminished in later cycles (cycles 3 and 5). Preliminary assessment of immunogenicity indicated an ADA incidence of 3.8% (7/186) with low titers ranging between 11.7 and 187 titer units and no impact on PK. Conclusions ABBV-383 exhibited a PK profile with relatively long half-life and low incidence of immunogenicity. Overall, sBCMA impacted (reduced) the ‘free’ ABBV-383 (pharmacologically active component) PK exposures only, with pronounced effect at lower doses and the effect is consistent with understanding of treatment dependent sBCMA dynamics over time. Determination of both ‘total’ and ‘free’ ABBV-383 serum concentrations allowed to demonstrate such underlying impact of sBCMA on PK.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic condition characterized by complement-mediated, life-threatening hemolysis and thrombosis which are associated with significant impacts on health-related quality of life (HRQoL). Pegcetacoplan is the first targeted complement component 3 (C3) therapy approved for adults with PNH (US) and adults with PNH plus anemia despite receiving a complement component 5 inhibitor (C5i) for ≥3 months (EU). In clinical trials including patients with PNH who were C5i-experienced or -naive, pegcetacoplan significantly improved levels of hemoglobin (Hb) and lactate dehydrogenase (LDH) and reduced transfusion burden. Pegcetacoplan had a favorable safety profile in parent studies and an ongoing long-term, rollover, open-label extension study (NCT03531255). Compliance with pegcetacoplan treatment was high across all clinical studies. In the US real-world OPERA and Adelphi PNH Disease Specific Programme™ (DSP) patient-reported outcomes (PRO) studies, improvements in levels of Hb and LDH, along with self-reported fatigue and cognitive outcomes, were observed. Pegcetacoplan treatment also led to reductions in the frequency and severity of PNH symptoms (including shortness of breath and fatigue) and improvements in social, physical, and emotional HRQoL domains in the US real-world Voice of the Patient PRO study. Further, both patient and physician satisfaction with pegcetacoplan treatment was high in the Adelphi PNH DSP study. However, to date, compliance and safety with pegcetacoplan treatment in the real-world setting have not been described. The objective of this real-world evidence review study was to evaluate compliance and safety with pegcetacoplan treatment in patients with PNH in the US post-marketing setting. Methods: Post-marketing data from the US, including the number of patients who received pegcetacoplan and reported safety events, were collected and analyzed from the pegcetacoplan Risk Evaluation and Mitigation Strategies (REMS) program which controls the distribution of pegcetacoplan and the pharmacovigilance safety database through May 13, 2023. Treatment compliance was calculated as the proportion of days a patient had the drug in possession, divided by the total number of days of follow-up, using central pharmacy prescription refill data. Thrombosis (a leading cause of death in patients with PNH prior to the availability of complement inhibitors) and meningococcal infections (a potential risk with complement inhibitors) were safety events of interest. To reduce the risk of serious meningococcal infections, clinical trial protocols and pegcetacoplan labeling required vaccination against Streptococcus pneumoniae; N meningitidis types A, C, W, Y, and B; and Haemophilus influenzae type B before starting treatment with pegcetacoplan. If pegcetacoplan treatment must be initiated before vaccination, the US label mandates prophylactic antibiotic use. In this study, the rates of thrombosis and meningococcal infection per 100 patient-years were estimated based on the total number of thrombosis and meningococcal infection events reported in the REMS program. Results: As of May 13, 2023, the cumulative pegcetacoplan exposure was 273.10 patient-years in the US post-marketing setting. Based on prescription refill data, compliance with pegcetacoplan treatment was ~98%. There were 2 confirmed thrombotic events reported and the incidence of thrombotic events was 0.73 events/100 patient-years in 273.10 patient-years. Similar to clinical trials, no meningococcal infections were reported in the US post-marketing setting. Conclusions: The high compliance rate and favorable safety profile of pegcetacoplan in the US post-marketing setting were consistent with clinical trial observations. These data, coupled with the effectiveness on hematologic parameters and improvements in symptoms and HRQoL reported in pegcetacoplan real-world PRO studies, support a positive benefit:risk profile for pegcetacoplan in the real-world setting.

Introduction: In Cohorts 1+2 of the ZUMA-1 Phase 1/2 study of axi-cel in R/R LBCL, 11% and 31% of patients (pts) experienced Grade ≥3 cytokine release syndrome (CRS) or neurologic evenets), respectively. To minimize the toxicities seen with axi-cel, a safety management cohort, Cohort 6 (N=40), was added to evaluate whether prophylactic (ppx) corticosteroids (CS) could decrease grade ≥ 3 CRS or ICANS. The 2-year update of ZUMA-1 Cohort 6 showed no grade ≥3 CRS and 15% grade ≥3 ICANS without any difference in objective response rate (ORR) or complete response rate (CR) when compared to cohorts 1+2 (Oluwole Blood 2022). The FDA had previously approved an update to the prescribing information for axi-cel to include use of ppx CS across all approved indications in January 2022. However, ppx CS is not a mandatory standard treatment and we sought to establish the clinical outcomes in the real-world practice. Methods: To assess the clinical outcomes of pts receiving ppx CS, we conducted a multicenter retrospective analysis of pts with R/R LBCL who were treated with axi-cel since the FDA approval of ppx CS in January 2022. Baseline characteristics, toxicities, and efficacy were compared between the no ppx and ppx CS groups. CRS and ICANS were graded based on ASTCT 2019 guidelines. Event-free survival (EFS) was defined as time from axi-cel infusion to progression, re-treatment, or death. Overall survival (OS) was defined as time from axi-cel infusion to death due to any cause. Results: A total of 66 pts at 5 centers received axi-cel between Jan 31, 2022, and June 20, 2023. Thirty-five (52%) pts received ppx CS, with a median age of 63 years (26-85 years). By histology, 75% (n=50) of the pts had DLBCL, 13.6% (n=9) had high grade B-cell lymphoma (HGBL), 9.1% (n=6) had transformed follicular lymphoma (TFL) and 1.5% (n=1) primary mediastinal LBCL (PMBCL). 59% of the pts (n=37) had IPI &gt;2 and 66% (n=43) had stage III/IV disease. The baseline characteristics at the time of apheresis are shown in Table 1 and were comparable between the 2 groups, except for more HGBL, fewer prior lines of therapy and longer median time from apheresis to axi-cel infusion in the ppx CS group. Among the entire cohort, only 37% (n=25) met ZUMA-1 eligibility criteria at the time of lymphodepletion, and 67% (n=44) needed bridging therapy. Any grade CRS occurred in 88% (n=58) of the pts, with grade ≥2 CRS in 38% (n=25). Any grade ICANS occurred in 55% (n=37) of the pts, with grade ≥2 ICANS in 41% (n=27). Any grade ICANS was significantly lower in the ppx CS group than the no ppx group (45.7% vs 65.5%). The rates of any grade CRS, grade ≥2 CRS, grade ≥2 ICANS, the median time to CRS onset, ICANS onset, CRS duration, and ICANS duration were comparable between the 2 groups. Tocilizumab and steroids use was similar between two groups with a trend towards less ICU admission in patients in the ppx CS group. Overall, 14 (21%) pts developed infectious complications within 30 days of axi-cel infusion. The day 30 ORR was 84% and was comparable between the 2 groups (77% in the ppx group vs 93% in the no ppx group). The CR was 45.7% in ppx CS group compared to 65.5% in no ppx group. At a median follow up of 219 days (27-1178), 37 (56.1%) pts had progressed and 25 (37.9%) pts had died. The number of days to progress was significantly lower in the ppx CS arm. The median EFS and OS were not significant between the 2 groups. Conclusions: This multicenter retrospective study showed that the efficacy of treatment with axi-cel in R/R LBCL did not decrease with the use of ppx CS. No significant differences in efficacy or CAR-T-associated toxicities were noted in the 2 groups, potentially due to selective use with patients at presumed higher risk of severe CRS and ICANS. A larger dataset and longer follow-up is needed for risk-stratified analysis and the study is ongoing.