Citations

Abstract Background: Prolonged cytopenias are a well-recognized complication following CAR-T therapy, leading to increased morbidity and healthcare utilization. Autologous SCB offers a potential strategy to promote hematologic recovery. We conducted a retrospective multi-institutional analysis across 18 centers comparing outcomes of SCB versus supportive care alone in RRMM patients who experienced prolonged cytopenias >30 days after CAR-T infusion. Methods: Patients were included if they received SCB within 1 year after commercial CAR-T between 6/2021 and 3/2024. To identify matched controls, we reviewed other CAR-T recipients from the same consortium and selected those with an absolute neutrophil count (ANC) of <0.72x109/L and platelet count of <21K at day 30 post-infusion-thresholds representing the 75th percentile of cytopenia severity in the SCB cohort. These criteria ensured control patients had comparable hematologic toxicity but without SCB. Hematologic recovery in the SCB cohort was assessed using the CIBMTR engraftment criteria. For the non-SCB (nSCB) group, cell counts were analyzed cross-sectionally at day 90 post-CAR-T and compared to the SCB cohort with Kruskal Wallis tests. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan Meier methods. Results: Of the 590 CAR-T recipients, 91 patients (15.4%) developed prolonged cytopenias; 39 patients received SCB and 52 did not. SCB patients more frequently had ISS stage III disease (23.1% vs. 11.5%), exrtamedullary disease (59% vs. 46.2%) and penta-refractory status (43.6% vs. 34.6%). The median number of prior lines of therapy was 6 in both cohorts. Thirteen patients (33.3%) in the SCB and 11 (21.2%) in the nSCB received high intensity infusional chemotherapy (DCEP/PACE/HyperCVAD). Pre-CAR-T cytopenias tended to be less frequent in the SCB vs. nSCB cohort: ANC <1000 in 5.1% vs. 13.5%, Hgb <8 in 23.1% vs. 21.2%, and platelets <50K in 28.2% vs. 40.4%. Median plasmacytosis in the bone marrow prior to CAR-T in the SCB group was 35% and 47.5% in the nSCB group. In the SCB cohort, 2 patients harbored DNMT3A mutations, one of whom had CCUS. Ide-cel was administered in 64.8% and cilta-cel in 35.2% of all patients. The rates and grades of cytokine release syndrome did not differ between groups. Six patients (15.4%) had HLH in the SCB group vs. none in the control group. All (100%) SCB patients received growth factor support; 58% also received TPO agonists. In the nSCB group, 43 patients (82.7%) received growth factor, and 16 patients (30.8%) received TPO agonists. Out of 24 pre-SCB bone marrow biopsies available, only 1 patient had relapsed MM while the remainder had hypocellular marrows. Median CD34+ cell dose was 2.93 million/kg (range: 1.76-23.55) administered at a median of 53 days post-CAR-T (range 24-265). All but one patient (97.4%) in the SCB group achieved hematologic recovery; median time to recovery was 24 days (range 9-87). No new toxicities attributable to SCB were observed. On day 90 post CAR-T infusion, SCB patients had higher median ANC (2.12 vs. 1.59x109/L, p=0.277), Hgb (10.6 vs. 8.7g/dL, p=0.002), and platelet counts (135 vs. 35K/L (p<0.001). Minimal residual disease negativity was achieved in 82.4% (SCB) vs. 83.3% (nSCB). Infections occured in 53.8% and 48.1% of SCB and nSCB cohorts. All serious infections occurred prior to SCB. There were 12 deaths in the SCB group (7 from disease progression, 2 from infection, 1 from neurotoxicity (NT), and 1 unknown) and 27 in the nSCB group (22 from progression, 3 from infection, 1 from HLH, 1 from NT). After a median follow-up period of 12.6 months in the SCB cohort and 11.6 months in the nSCB arm, the mPFS was 11.0 months and 8.2 months, respectively. The mPFS was 10.6 months (SCB) and 5.8 months (nSCB) (p=0.216), and 11.0 months (SCB) and 10.9 months (nSCB), for ide-cel and cilta-cel treated-patients, respectively. Median OS was not reached vs.12.3 months in the SCB vs. nSCB groups, respectively. Conclusion: Overall, SCB was safe and effective in promoting rapid hematologic recovery in nearly all patients. Compared to controls, SCB recipeints had significantly higher Hgb and platelet levels by day 90 post-CAR-T infusion. SCB was associated wih a near doubling of PFS in patients who received ide-cel, though interpretation is limited by non-randomized design and small sample size. Further study is needed to optimize paient selection, timing, and integration of SCB into CAR-T care.

Abstract Background Patients (pts) with multiple myeloma and CNS involvement (CNS MM) have poor outcomes, and we recently showed that CAR-T has activity and is reasonable in this population (Gaballa et al., 2025). We sought to evaluate the safety and efficacy of Bispecific T-cell engagers (BsAbs) in CNS MM pts, with specific interest in evaluating ICANS. Methods We conducted a retrospective study of CNS MM pts treated with BsAbs via the MM immunotherapy consortium. Primary endpoints were toxicity rates, with a specific focus on ICANS. Secondary endpoints were systemic responses, CNS responses, and survival outcomes. CNS MM was defined as involvement of the brain parenchyma, spinal cord tissue, leptomeningeal disease, or CSF positivity. CNS response was determined based on CSF and imaging, as complete CNS response, partial CNS response, and non-response/progression. Results The study included 24 pts from 13 US institutions treated with teclistamab (33%), talquetamab (50%), elranatamab (17%), and were used as monotherapy in 83% while 17% received them in combination with either daratumumab or IMiDs. The median age was 64.5 (range 41-82), 50% female, 79% white, and 17% black. High-risk cytogenetics were identified in 39%, 4% had prior primary PCL, and 21% had secondary PCL (2 active within 30 days of BsAb initiation). All pts were triple-refractory, 33% were penta-refractory, and 39% had non-CNS EMD. Pts received a median of 5 prior lines of therapy (IQR 4-7), 71% prior transplant, and 21% prior CAR-T. Prior BCMA therapy was received in 83% of the talquetamab group and 17% of the BCMA BsAbs group (teclistamab and elranatamab). CNS disease was determined based on both imaging and CSF findings in 58%, imaging only in 33%, and CSF only in 8%. Site of CNS disease included 42% brain/cranial nerves, 13% spinal cord, or 46% with both. CNS disease was diagnosed prior to BsAb in 19 pts, with a median interval of 46 days (IQR 7-234), and 3 pts were identified within 2 weeks after BsAb initiation. Two pts identified at days 68 and 121 were included in the safety evaluation but excluded from the efficacy assessments. One pt received teclistamab and intrathecal chemotherapy (IT chemo) as a bridge to CAR-T and achieved a complete CNS response before CAR-T. CNS-directed therapy consisted of: 30% radiotherapy (RT), 30% IT chemo, 13% RT + IT chemo, 9% RT + surgery, and 4% steroids. CRS grade (G) 1-2 occurred in 50%, with no G3-4 CRS. ICANS G 1, 2, and 3 occurred in 13%, 21%, and 4%, respectively, with no G 4 ICANS. One pt developed delayed parkinsonism, and another developed leukoencephalopathy; both had CNS MM diagnosed pre-BsAbs and achieved a CNS response (1 complete, 1 partial). Infections occurred in 67% of pts, with 42% being severe, and 1 infection-related death. The systemic ORR of 18 evaluable pts was 67%, including 22% CR, 17% VGPR, and 28% PR. The overall CNS response of 19 evaluable pts was 58%, including 37% complete CNS response and 21% partial CNS response. Of 11 pts achieving a CNS response, 82% didn't have subsequent CNS progression. In 9 pts achieving CNS response after BsAb initiation, the median time to CNS response was 0.9 months (range 0.03-2.8), with an unreached median duration of CNS response. With a median follow-up of 11 months, the median PFS was 5.0 months (95% CI 2.5-NA) and OS was 12.2 months (95% CI 7.7-NA). No significant difference in median PFS (10.6 vs 4.6 months, p=0.11) or OS (20.2 vs 9.3 months, p=0.37) was observed between BCMA BsAbs (n=11) and talquetamab (n=11). Due to small sample limitation, no significant difference was observed in the median PFS (4.6 vs 8.2 months, p=0.48) or OS (20.2 vs 9.9 months, p=0.73) between BsAb monotherapy (n=19) and BsAb combination therapy (n=3). One pt who received teclistamab as a bridge to CAR-T achieved a complete CNS response and remains progression-free to date, demonstrating the best long-term outcome with a PFS of 674 days. Conclusions Our study demonstrates that BsAb use in pts with CNS MM is safe without increased incidence of ICANS. The use of BsAbs in combination with a multimodal CNS-directed approach led to an overall CNS response rate of 58% and an unreached median duration of CNS response. Previous studies (Gaballa et al., 2025) reported a 100% CNS response rate with CAR-T. In this study, 1 pt treated with BsAb as a bridge to CAR-T had the longest PFS, warranting further research to evaluate this combination's efficacy in this very high-risk population.

ObjectiveHigh‐throughput DNA sequencing of the paranasal sinus microbiome has potential in the diagnosis and treatment of sinusitis. The objective of this study is to evaluate the use of high‐throughput DNA sequencing to diagnose sinusitis of odontogenic origin.Study DesignCase series with chart review.SettingSingle tertiary care academic medical center.Subjects and MethodsA chart review was performed of DNA sequencing results from the sinus aspirates obtained under endoscopic visualization in 142 patients with sinusitis. The identification of any potentially pathogenic bacteria associated with oral flora in a sample was classified as a positive result for sinusitis of odontogenic etiology. The sensitivity, specificity, and predictive values of using high‐throughput DNA sequencing to diagnose sinusitis of odontogenic etiology were determined, with the patient’s computed tomography sinus scan as the reference standard. On computed tomography scans, an odontogenic source was determined by the presence of a periapical lucency perforating the schneiderian membrane.ResultsSeven of the 142 patients enrolled in this study had an odontogenic source based on computed tomography scans. Relative to this reference standard, high‐throughput DNA sequencing produced a sensitivity of 85.7% (95% CI, 42.1%‐99.6%), a specificity of 81.5% (95% CI, 73.9%‐87.6%), a positive predictive value of 19.4% (95% CI, 13.1%‐27.7%), and a negative predictive value of 99.1% (95% CI, 94.7%‐99.9%).ConclusionThis study supports the use of high‐throughput DNA sequencing in supplementing other methods of investigation for identifying an odontogenic etiology of sinusitis.