Citations

9065 Background: Rearranged during transfection ( RET) gene alterations are the oncogenic driver in diverse tumor types, including RET fusions identified in 1-2% of non-small cell lung cancers (NSCLC). While RET-selective tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are effective, acquired drug resistance remains a challenge. Here, we report the initial results from the RETgistry, an international consortium aimed at elucidating mechanisms of resistance to RET TKIs across RET-altered solid tumors. Methods: This was a retrospective analysis performed across 16 institutions. Patients (pts) were eligible if they had advanced solid tumor harboring an oncogenic RET alteration, received ≥1 RET TKI with disease progression, and underwent resistant tumor or liquid biopsy for next-generation sequencing (NGS). Results: A total of 103 time-distinct biopsies (62 tissue, 30 plasma, 11 paired tissue/plasma) were included in analysis, obtained from 88 pts with progression on a RET-selective TKI [selpercatinib (n = 70), pralsetinib (n = 14), selpercatinib and pralsetinib sequentially (n = 4)]. Pts had the following tumor types: 72 NSCLC (69% KIF5B-RET, 21% CCDC6-RET, 10% other RET fusion), 13 medullary thyroid cancer (TC) (54% RET M918T, 46% other RET mutation), and 2 papillary and 1 anaplastic TC (all, RET fusion). Median age was 58 (range, 21-86); 48% were male with 89% never/light smokers. Median duration of RET TKI preceding biopsies [first-line, n = 32 (31%); second-line, n = 42 (41%); third-/greater-line, n = 29 (28%)] was 16.5 months (mos) (95% CI, 14.0-19.6); median PFS was 14.1 mos (95% CI, 9.3-17.0). Resistant biopsies were obtained at median 15.0 mos from TKI initiation (range, 1.8-58.8). Acquired RET mutations were detected in 14 (14%), most common being G810 substitutions in 12 (12%). Potential off-target resistance gene alterations identified in 43 cases (42%) included MET amplification (14%), BRAF V600E or fusion (2%), KRAS gain or mutation (5%), ERBB2 amplification (2%), EGFR amplification (3%), ROS1 fusion (1%), and activating PIK3CA mutation or PTEN loss (4%). No resistant lung cancer biopsy demonstrated small cell transformation. The duration of TKI therapy (HR 0.64, p = 0.11) or PFS (HR 0.75, p = 0.33) did not differ according to the presence of on-target vs off-target resistance. NGS analyses of pre-RET-selective TKI tumors (n = 92) revealed frequent co-occurring alterations in TP53 (29%) and CDKN2A/B (12%). Conclusions: On-target resistance to RET inhibition due to acquired RET mutations was less common than off-target resistance, identified in 14%. The majority of RET TKI resistance is mediated by off-target mechanisms such as bypass receptor tyrosine kinase activation. Further studies are warranted to enable the development of therapeutic strategies to address resistance in pts with RET-altered tumors. The RETgistry accrual and data analyses continue.

e20646 Background: Thymic carcinomas tend to be aggressive malignancies with variable patterns of immunostaining. We aimed to assess whether the outcome of patients with thymic carcinomas was associated with immunoreactivity for conventional and emerging immunohistochemical markers of thymic carcinoma versus thymoma. Methods: Scoring of CD5, CD117, EZH2, POU2F3, BAP1, and MTAP immunohistochemistry on whole slide sections was compared to overall survival (OS) and progression free survival (PFS) for 36 thymic carcinoma patients, 28 of whom had complete tumor resection and 8 of whom had incomplete tumor resection. Results: Positive CD5 staining (defined as staining in ≥50% of tumor cells) was present in 13/36 cases (36%) and was significantly associated with longer OS (P = 0.005, hazard ratio = 0.18, CI 0.03-0.63) but not PFS (P = 0.14, hazard ratio = 0.48, CI 0.16-1.26), whereas the other markers were not significantly associated with OS or PFS. Positive CD5 staining remained significantly associated with OS in squamous cell carcinoma subgroup analysis (n = 23, HR = 0.17, CI 0.03-0.65, P = 0.009), patients who did not receive neo-adjuvant treatment (n = 24, HR = 0.21, CI 0.03-0.85, P = 0.03) and after adjusting for incomplete resection (HR = 0.20, CI0.03-0.73, P = 0.01), M1 stage (HR = 0.19, CI 0.03-0.71, P = 0.01) or neoadjuvant treatment (HR = 0.19, CI 0.03-0.71, P = 0.01) in bivariate models. Positive CD5 staining was also significantly associated with age ≥60 years, absence of neoadjuvant treatment, and positive POU2F3 staining. Conclusions: CD5 staining in ≥50% of tumor cells was significantly associated with longer OS for thymic carcinoma patients. Our study supports the notion that CD5 immunohistochemistry may have utility as a prognostic marker for thymic carcinomas.

8024 Background: Minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). MRD is usually assessed in the bone marrow (BM) by flow cytometry or NGS. MRD by FDG PET/CT provides a global representation of the tumor burden, including response assessment of extramedullary disease. We examined MRD status in MM pts using both BM and PET/CT at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CAR-T between 4/2018 and 12/2022. All PET/CT scans were assessed by radiologists. BM MRD was assessed by flow cytometry with a sensitivity of 10-5. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Results: Among the 157 CAR-T pts, including 89 pts who received FDA-approved CAR-T, median age was 63 years, 59% (92/157) were males, 42% (66/157) had high risk cytogenetics with median of 5 prior lines of therapy, 36% (57/157) had plasmacytoma. Incidence of CRS was 83%, 5% grade ≥ 3 CRS. Incidence of ICANS was 19%, 4% grade ≥ 3 ICANS. CR/sCR rate was 37%. One hundred and thirty-seven pts (87%) had evaluable BM at month (mo) 1, 85% (117/137) were BM MRDneg at mo 1. Baseline demographics were comparable between the two groups except age, % BM plasma cells and use of bridging therapy. Among the MRDneg pts, CR/sCR rate was 44% (51/117) and 95% (111/117) had sFLC below normal. At median follow-up of 13.8 months, median PFS among pts with BM MRDneg at 1 mo was 12 mo (95% CI: 11, 30) vs 3 mo (95%CI: 2, 7) for BM MRDpos (p<0.001). Median OS among pts with BM MRDneg at 1 mo was 34 mo (95% CI: 24, NR) vs 22 mo (95%CI: 7, NA) for BM MRDpos (p<0.01). At month 1, 112 pts had both BM and PET/CT assessments available, 64/112(57%) were both BM MRDneg/PET MRDneg, 38/112 (34%) were MRDneg for either BM or PET and 10/112 (9%) were positive for both BM and PET (MRDpos/PET MRDpos). Baseline demographics except age were comparable between the 2 groups (Table). Rate of conversion from MRDpos to MRDneg was low. Rate of sustained BM and PET MRDneg at mo 12 was 44% (8/18). The median PFS and OS for BM MRDneg/PET MRDneg was significantly longer as compared to others (Table). Conclusions: Achieving FLC below normal, BM MRDneg and PET MRDneg at 1 month, regardless of IMWG response at that time, is prognostic for both PFS and OS in MM pts receiving CAR-T. Failure to achieve any of these confers poor prognosis. [Table: see text]

7530 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach currently under study for relapsed refractory (R/R) hematologic malignancies. The engineered Vesicular Stomatitis Virus VSV-IFNβ-NIS used in this study encodes interferon beta (IFNβ) and sodium iodine symporter (NIS). Virally-encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. Herein, we report the updated results of the phase 1 clinical trial NCT03017820 of a one-time administration of systemic VSV-IFNβ-NIS among patients (pts) with R/R multiple myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML) with particular focus on the TCL cohort treated at the highest dose level (DL4) without Ruxolitinib. Methods: VSV-IFNβ-NIS was administered as a single IV dose following a classical 3+3 phase I trial, starting at 5e9 TCID50 DL1 through 1.7e11 TCID50 DL4. A dose expansion cohort of 8 additional R/R TCL pts was added at DL4 in view of an initial signal of activity. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: To date, a total of 43 pts received VSV-IFNβ-NIS: MM (N=21), TCL (N=21) and AML (N=1). In the TCL cohort: at DL4 Group A (no Ruxolitinib), 12 pts were registered, but only 11 pts were treated (mycosis fungoides (MF) N=3; ALK- ALCL N=1; PTCL-NOS N=2; AITL N=4; Nodal PTCL, TFH N=2; ages 33-79). These pts received a median of 3 lines of therapy (range: 1-5). No dose limiting toxicities were observed. Grades 3 and higher AEs were hematologic with transient lymphopenia (63.6%), neutropenia (36.4%) being the most common. The non-hematologic AEs observed included unique toxicities such as CRS grades 1-2 (81.8%); the transient transaminitis grade 1-2 (36.4%) and grade 3 (27.3%) along with thrombocytopenia grade 1-2 (63.6%) and grade 3 (18.2%) were a reflection IFNβ toxicity. All the AEs observed were short lived. Responses were seen in pts with PTCL. At DL4, in pts with systemic PTCL (N=9), there were 5 responses including 3 complete responses (CR) with two long-lasting at 24 months, an ongoing 15 month CR, and a 5 month CR, and 2 partial responses (PR) lasting 5 months in one pts and 6 months in the other. Conclusions: These updated results of single agent VSV-IFNβ-NIS which include pts with PTCL treated at the highest dose level and a dose expansion cohort demonstrates not only the safety of VSV-IFNβ-NIS but also a strong efficacy signal in pts with PTCL with impressive durable responses. Two expansion cohorts at DL4 have been added (20 additional PTCL, 10 B-cell lymphoma pts) to obtain additional data on tolerability and efficacy and biomarkers of response in these pts. Clinical trial information: NCT03017820 .

7515 Background: Outcomes are poor for patients (pts) with cHL who develop R/R disease after first-line (1L) chemotherapy ± radiotherapy (RT). Salvage tx that attain high event-free survival (EFS) rates and minimize late toxicity by omitting high-dose chemotherapy (HDCT)/auto-HCT are needed. CheckMate 744 (NCT02927769) is the first multicenter phase 2 study evaluating a risk-stratified, response-adapted salvage tx with nivo + BV in CAYA with R/R cHL. In the standard-risk cohort, complete molecular response (CMR) rate before consolidation with HDCT/auto-HCT was 94% (Harker-Murray et al. Blood 2022). With highly active salvage tx, pts in low-risk cohort could achieve high EFS without HDCT/auto-HCT; we report data from this cohort. Methods: Pts were aged 5–30 y and had ≤ 3 cycles (C) of 1L anthracycline-based systemic tx. Risk stratification was described in Harker-Murray et al. Pts received 4C of nivo + BV induction. Pts with CMR received additional 2C nivo + BV before involved-site radiation therapy (ISRT) consolidation (dose, 30–30.6 Gy). Pts with suboptimal response received 2C BV + bendamustine intensification; pts with CMR proceeded to ISRT consolidation. Primary endpoints: CMR rate (Lugano 2014) any time before ISRT and 3-y EFS rate, both per blinded independent central review (BICR). For CMR and overall response rate (ORR), a 90% confidence interval (CI) was used per statistical plan. Results: Among 28 pts treated with nivo + BV, median (range) age was 17 (6–27) y; 64% of pts were aged < 18 y. Most (64%) pts had stage II disease at relapse; 82% had relapse ≥ 12 mo after 1L tx, 2 pts had prior RT. Median (range) follow-up was 31.9 (2.2–55.3) mo. CMR, ORR, 3-y EFS and PFS rates are shown in Table. Median duration of response was not reached; 87% of pts had sustained response at 36 mo’ follow-up. Efficacy outcomes were comparable in the pediatric population (CMR per BICR before ISRT, 88.9%; 3-y EFS rate, 78.3%). During induction, 22 (78.6%) pts had treatment-related adverse events (TRAEs; grade 3/4, 25.0% pts; hematologic, < 10% pts; immune-mediated, 21.4%). Serious AEs leading to discontinuation included rash, pyrexia, and acute kidney injury (1 pt each). Conclusions: The findings demonstrate that most CAYA with low-risk R/R cHL can be salvaged with chemoimmunotherapy with a favorable toxicity profile, and do not require HDCT/auto-HCT. Clinical trial information: NCT02927769 . [Table: see text]

7501 Background: In patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based regimens, achieving CR with current treatment is uncommon. New therapies that achieve deep and durable responses are needed. We report the primary analysis of the phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study evaluating liso-cel in pts with R/R CLL/SLL. Methods: Pts must have received at least 2 prior lines of therapy, including a BTKi. Eligible pts received liso-cel at a target dose of either 50 (DL1) or 100 (DL2) × 106 CAR+ T cells. The primary endpoint was rate of CR and CR with incomplete marrow recovery (CRi) by IRC per 2018 iwCLL criteria in the prespecified subset of efficacy-evaluable pts with disease progression on BTKi and ven failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H0]: ≤ 5%). Key secondary endpoints were ORR (H0: ≤ 40%) and rate of undetectable minimal residual disease (uMRD; 10−4) in blood (H0: ≤ 5%). Results: Of 137 leukapheresed pts, 117 received liso-cel (safety set), 96 (DL1 = 9; DL2 = 87) were efficacy evaluable, and 53 (DL1 = 4; DL2 = 49) were in the PEAS. In the safety set, median (range) age was 65 y (49–82), 83% had high-risk features, median (range) lines of prior therapy was 5 (2–12), and all pts had prior BTKi. Median (range) on-study follow-up was 21.1 mo (0.4–55.6) for the safety set. In the PEAS at DL2, the primary endpoint of CR/CRi rate was met at 18.4% (95% CI, 8.8–32.0; 1-sided P = 0.0006; Table). ORR was 42.9% and was not statistically significant (95% CI, 28.8–57.8; 1-sided P = 0.3931). The uMRD rate was 63.3% in blood and 59.2% in marrow. Median (95% CI) DOR was 35.3 mo (11.01–not reached [NR]) with a median follow-up of 19.7 mo. Median duration of CR/CRi was NR. In the safety set, rate of any-grade CRS was 84.6% (gr 3, 8.5%; no gr 4/5) and neurological events (NE) was 45.3% (gr 3, 17.9%; gr 4, 0.9%; no gr 5); 69.2% received tocilizumab and/or corticosteroids for CRS/NEs. Rate of gr ≥ 3 infections, hypogammaglobulinemia, and prolonged cytopenia was 17.1%, 15.4%, and 53.8%, respectively. One death related to liso-cel was due to hemophagocytic lymphohistiocytosis. Liso-cel exhibited rapid in vivo expansion and was detected by qPCR in blood up to 36 mo after infusion. Conclusions: Liso-cel demonstrated durable CR/CRi, high uMRD rates, and a manageable safety profile in pts with heavily pretreated, high-risk R/R CLL/SLL and high unmet need. Clinical trial information: NCT03331198 . [Table: see text]

7019 Background: High-risk essential thrombocythemia (HR ET) is characterized by thrombocytosis, thrombohemorrhagic events and systemic symptoms. Pts can experience intolerance, inadequate response or loss of response to first-line cytoreductive therapies (hydroxyurea [HU] or interferon alfa-2a). BET protein inhibition is a novel therapeutic strategy that downregulates inflammatory cytokines and may inhibit differentiation and proliferation of abnormal megakaryocytes involved in ET pathogenesis. Results from the Phase 2 MANIFEST study (NCT02158858) suggested potentially encouraging clinical efficacy in pts with myelofibrosis treated with Pelabresib (PELA), an oral, small-molecule, investigational BET inhibitor. Here we present preliminary results from MANIFEST Arm 4 investigating PELA monotherapy in HR ET refractory or intolerant to HU. Methods: Eligible pts had platelets > 600 x 109/L and ≥ 2 symptoms (average score ≥3/ TSS≥15). Pts received PELA monotherapy 225 mg QD. The primary endpoint was complete hematologic response (CHR; normalization of platelet count (≤400 x 109/L), WBC count (≤10 x 109/L) confirmed after one cycle [after 3 weeks]) and normal spleen size. Secondary endpoints included partial HR (PHR; platelets 400–600 x 109/L and WBC ≤10 x 109/L), symptom improvement (≥50% TSS reduction) and safety. Results: As of July 2022, 20 pts with HR ET were treated: median age 64 yrs (42–83), median Hgb 13 (10–16) g/dL, median platelet count 772 (418–1255) x 109/L and median TSS 32.7 (6.9–123). The majority of pts had a hematologic response (90% [18/20] unconfirmed CHR or PHR); confirmed CHR was observed in 40% (8/20) (Table). Median platelet and WBC count at Wk 12 was 446 x109/L and 8.2 x 109/L, respectively. TSS reduction was reported in 86% (12/14 pts); median TSS reduction at Wk 12 was –31%. Hgb levels remained stable through Wk 24. The most common nonhematologic AEs were nausea (60%; 10% Gr 3), diarrhea (35%; 5% Gr 3) and dysgeusia (35%; no Gr 3). Hemorrhagic or thromboembolic events were reported in 30% pts (15% Gr 3). No events of thrombocytopenia and no Gr 4 events or higher were reported. Conclusions: Preliminary results from Arm 4 of the MANIFEST study suggest potential clinical benefit with PELA monotherapy in pts with HR ET refractory or intolerant to HU as supported by hematologic responses and symptom improvement. Safety results are consistent with the known safety profile of PELA and as expected in the underlying study population. Clinical trial information: NCT02158858 . [Table: see text]

3082 Background: CLDN6, a member of the claudin family of tight junction proteins, is expressed at high levels in multiple human malignancies and has little to no expression in normal tissues. This expression profile makes CLDN6 an ideal target for development of new therapeutics. TORL-1-23 is first-in-class ADC targeting the tumor-specific antigen CLDN6. Methods: TORL123-001 (NCT05103683) is an ongoing, 2-part, first in human study to characterize the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of TORL-1-23 monotherapy in participants with advanced solid tumors. Serum pharmacokinetics (PK), immunogenicity and clinical efficacy are also assessed. TORL-1-23 is administered as a 30-minute IV infusion once every 3 weeks in 21-day cycles. During Part 1 (Dose Escalation), cohorts of 1 to 6 participants are evaluated at each dose level according to an accelerated titration design. In Part 2 (Dose Expansion), several cohorts of patients with CLDN6-expressing cancers will be evaluated to confirm the RP2D in ovarian cancer, NSCLC, and other CLDN6-expressing cancers using a CLDN6 IHC companion diagnostic. Results: As of 01FEB2023, 22 patients with ovarian (n=18), testicular (n=3), and endometrial (n=1) cancers were enrolled and treated across 8 dose levels ranging from 0.2 to 2.4 mg/kg IV every 3 weeks. 95% of pts had received ≥ 3 prior lines of treatment in the metastatic setting. The most common treatment-related adverse events were Gr1/2 fatigue (n=5), Gr1 peripheral neuropathy (n=4), and Gr1 nausea (n=3). No DLTs have been reported and no dose reductions have been required. Preliminary PK data demonstrate sustained exposure of TORL-1-23 ADC over the 21 day dosing interval and low levels of serum MMAE indicating low off-target MMAE exposure outside of tumor. Partial responses (PR) were observed in 4/17 efficacy evaluable participants with CLDN6+ disease (3 ovarian, 1 testicular). Dose escalation is ongoing and updated results will be presented. Conclusions: TORL-1-23 has a favorable safety/tolerability profile and PK characteristics with preliminary antitumor activity in pts with heavily-pretreated CLDN6-expressing ovarian and testicular cancers. Doses above the historic MTD for MMAE containing ADCs may be explored given the safety/tolerability and PK data observed up to 2.4 mg/kg. Dose finding is ongoing to identify the MTD and optimal doses for subsequent development. Clinical trial information: NCT05103683 .

2529 Background: Tumor expression of the antiphagocytic protein CD47 (integrin associated protein) may lead to immunotherapy resistance (IO-R). PF-07257876 is a novel, IgG1, Fc-active, bispecific antibody targeting CD47 and PD-L1 designed to reverse IO-R, decrease anemia risk, and eliminate a priming dose. We report a Phase 1 dose escalation study (NCT04881045) in patients (pts) with advanced solid tumors, both IO-refractory and IO-naïve. Methods: The study enrolled pts ≥18 yrs with advanced non–small-cell lung carcinoma (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN) with PD-L1 expression >1% post anti-PD-1/PD-L1 therapy. Pts with other PD-L1+ tumors known to express CD47 were included (prior IO not required). Pts received PF-07257876 at escalating dose levels in 28-day cycles. Primary objectives were safety (dose-limiting toxicity [DLT] rate), tolerability, and determination of Recommended Phase 2 Dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), blood receptor occupancy (RO), CD47 levels by immunohistochemistry (IHC), tissue biopsy findings, and objective response rate (ORR) per RECIST v.1.1. Results: As of 20OCT2022, 18 pts were enrolled (NSCLC: n = 6; SCCHN: n = 4; other: n = 8). Median (range) age 68 (46–79) yrs. PF-07257876 was given at ascending doses, 150-2400 mg by subcutaneous (SC) injection or SC infusion every 2 weeks. 16 (89%) pts had treatment-related adverse events (TRAEs): Grades 1/2: n = 12 (67%); Grade 3: n = 1 (6%); Grade 4: n = 3 (17%); no Grade 5. Most common TRAEs: injection site reaction/erythema (n = 13, 72%), thrombocytopenia (n = 6, 33%), anemia (n = 5, 28%), and nausea (n = 4, 22%). DLTs occurred in 2 of 3 pts at the highest tested dose (Grade 4 neutropenia and thrombocytopenia, n = 1; Grade 4 thrombocytopenia, n = 1; both pts recovered). One pt with IO-R SCCHN had a confirmed partial response (duration of response 16 wks). ORR was 5.6% (1/18). Drug exposure increase after 1st dose was not dose proportional. Blood RO was > 95% for PD-L1 and > 70% for CD47 with drug exposure. All pts’ baseline CD47 IHC levels were moderate to high. Pharmacodynamics cytokine profiling showed notable dose-response increases of IFNg, TNFa, CXCL9/10, CCL3/4, without IL-6 increase. Conclusions: PF-07257876 was well tolerated with manageable toxicity. Incidence and grade of anemia or thrombocytopenia were manageable. Target engagement of CD47 and PD-L1 in peripheral blood was high. Innate and adaptive cytokine modulation was observed. Antitumor activity was modest. Expansion is ongoing at 1800 mg. Clinical trial information: NCT04881045 .

1533 Background: FDA-approved chimeric antigen receptor T-cell (CAR-T) and bispecific T cell engager (TCE) therapy are most commonly managed inpatient. Here we report our experience with hospital-based outpatient (HBO) management of patients (pts) receiving FDA-approved CAR-T or TCE and a predictive model for increased risk of early hospitalization (≤3 days post CAR-T). Methods: We reviewed the outcomes of pts who received FDA-approved CAR-T (axi-cel, brexu-cel, ide-cel, cilta-cel) or TCE (teclistamab) in the HBO unit between 3/2021 and 1/2023 at Mayo Clinic, Rochester. Results: HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. CAR-T and TCE are given on HBO followed by monitoring per REMS and as clinically needed until admission criteria is met. Remote patient monitoring (RPM) tools were used as part of outpatient monitoring. Out of 169 CAR-T pts, 87 (51%) were dosed with new indication/products (follicular lymphoma, mantle cell lymphoma, myeloma). Among those, 80 (92%) pts were dosed outpatient, among whom 21 (27%) were never hospitalized. CRS and ICANS incidences were comparable to that reported in registration studies. Median time to first admission from CAR-T infusion was 1 day (range, 0-9), with 31% (n=18/59) of admissions after day 3 post infusion. The most common cause of hospitalization was fever (n=40, 59%). Median length of hospital stay was 4 days (range, 1-49). Median time to tocilizumab (n=45, 80%), steroid (n=1, 2%), escalation of oxygen support (n=7, 12%), vasopressor (n=2, 3%), ventilator (n=1, 2%), hemodialysis (n=1, 2%) and ICU transfer (n=3, 5%) was 1 day (range, 0-31) after first admission. Use of bridging therapy, elevated CRP and LDH were predictive of early admission (ROC AUC 0.62). Four pts received teclistamab on HBO and enrolled in RPM. Data from more pts will be reported at ASCO. Conclusions: Our expanded study in CAR-T and TCE confirms that HBO is feasible and that CAR-T and TCE can be safely dosed outpatient. Approximately 31% of pts were admitted after 3 days from CAR-T infusion, and 27% of our pts were never admitted. Variables associated with aggressive disease can predict early hospitalization in pts receiving FDA-approved CAR-T. Extension of HBO practice to TCE is feasible.[Table: see text]