Citations

Abstract Fields, JB, Jones, MT, Kitts, SE, King, EL, and Jagim, AR. Relationships between disordered eating, body dissatisfaction, and low energy availability in women collegiate athletes. J Strength Cond Res 40(2): e164–e171, 2026—Women collegiate student-athletes face unique challenges regarding nutrition, body image, and athletic performance, increasing their risk for low energy availability (LEA), disordered eating (DE), and body dissatisfaction (BID). However, limited data exist exploring LEA, DE, and BID across a variety of women's sports. Therefore, the purpose of this study was to evaluate the prevalence of and relationships among LEA risk, DE behaviors, and BID in women collegiate athletes from multiple sports. Division I, II, and III women student-athletes ( n = 115) participated in this cross-sectional, descriptive study. Athletes completed the low energy availability for females questionnaire (LEAF-Q), eating attitudes test (EAT-26), muscularity-oriented eating test (MOET), and body dissatisfaction items from the eating disorder examination questionnaire (EDE-Q) to assess LEA risk, DE behaviors, and BID, respectively. Sixty-four percentages of athletes were at risk for LEA, with the highest prevalence in volleyball (100%), wrestling (68%), lacrosse (67%), and cross country (57%). However, only 8% of athletes were classified at risk for eating disorders. Notably, 81 and 84% of athletes reported body weight and shape dissatisfaction, respectively, which was strongly associated with disordered eating behaviors (EAT-26: r = 0.707; MOET: r = 0.723, p < 0.001). These results show a high prevalence of LEA risk and BID across athletes, with DE behaviors strongly linked to body image concerns. Despite a high LEA risk among athletes, clinical eating disorder risk remained low, suggesting that undereating may often be unintentional. Targeted interventions focused on nutritional education, body image, and psychological support are critical for improving health and performance outcomes among collegiate women student-athletes.

Abstract Immune checkpoint inhibitor–associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016 and 2023 at 29 US hospitals across 7 major cancer centers to identify patients with ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86 467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage IV cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (interquartile range [IQR], 4-18) after ICI initiation, with a median nadir platelet count of 41 × 109/L (IQR, 17 × 109/L to 64 × 109/L). Patients were treated with glucocorticoids (n = 106 [49.5%]), immune globulin (n = 39 [18.2%]), and thrombopoietin receptor agonists (n = 29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP than those without ICI-ITP (adjusted hazard ratio, 2.96 [95% confidence interval, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide, to our knowledge, the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.

OBJECTIVE Glucagon-like peptide-1 (GLP-1) agonists are established therapeutics for weight loss that are increasingly used for BMI optimization prior to spine surgery. However, emerging evidence has suggested that GLP-1 agonists might reduce bone mineral density (BMD), increasing the risk of postoperative biomechanical complications. CT-based Hounsfield units (HUs) have gained popularity as a method for measuring spinal BMD. The aim of this study was to evaluate the effects of GLP-1 agonist–induced weight loss on spinal BMD as measured by opportunistic CT-based HUs. METHODS Patients who were treated with any GLP-1 agonist (2017–2022) for > 3 months were retrospectively identified. Patient body weight (BW), BMI, and HU measurements in the L1 vertebral body were measured before and after GLP-1 therapy. Patients were grouped according to the percentage of weight loss during GLP-1 therapy. One-way ANOVA was used to compare the mean changes in spinal HUs across the groups. RESULTS Among the 102 included patients, the mean ± standard error of the mean BW reduction was 14.5 ± 2.5 kg over 15.9 ± 1.2 months of GLP-1 agonist therapy. Of these, 7 patients (6.9%) lost > 20% BW (mean decrease of 31.9 ± 7.0 HU, p = 0.011), 14 (13.7%) lost 15%–20% BW (mean decrease of 19.1 ± 8.3 HU, p = 0.038), 14 (13.7%) lost 10%–15% BW (mean decrease of 12.2 ± 5.1 HU, p = 0.036), 24 (23.5%) lost 5%–10% BW (mean decrease of 15.7 ± 3.3 HU, p < 0.0001), 26 (25.5%) lost < 5% BW (mean decrease of 14.7 ± 6.0 HU, p = 0.022), and 17 (16.7%) gained BW during GLP-1 therapy (mean decrease of 6.3 ± 5.0 HU, p = 0.229). One-way ANOVA testing did not show a significant difference in HU reduction across the weight loss groups (F = 1.12, p = 0.355). In addition, there was a significant correlation between the decrease in L1 HUs and the duration of GLP-1 therapy (r = −0.38, p = 0.0001) but not the amount of weight loss (r = −0.18, p = 0.070). In the multivariate analysis, the duration of GLP-1 therapy (p = 0.032) was a significant independent predictor of vertebral HU reduction, but the amount of weight loss (p = 0.664) was not. CONCLUSIONS Despite similar pretreatment BW and HU measurements, all weight loss groups had significant decreases in vertebral HUs following GLP-1 agonist therapy, with a significant correlation observed between HU reduction and treatment duration. This suggests that long-term GLP-1 agonist therapy can significantly diminish spinal BMD regardless of the amount of weight loss achieved.

Abstract Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non–busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

Abstract Introduction Bruton tyrosine kinase inhibitors (BTKis) have changed the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Efficacy was demonstrated for zanubrutinib and ibrutinib in high-risk R/R CLL patients in the ALPINE (NCT03734016) trial, for ibrutinib and acalabrutinib in the ELEVATE-RR (NCT02477696) trial, and for acalabrutinib in the ASCEND (NCT00135226) trial. While there is limited head-to-head comparative trial data of all covalent BTKis in the treatment of high-risk R/R CLL, a previously published network meta-analysis (NMA) used data from the ALPINE, ELEVATE-RR, and ASCEND trials, and reported that zanubrutinib demonstrated significantly improved relative efficacy compared to ibrutinib and acalabrutinib in high-risk R/R CLL (Shadman 2025). Within this NMA, high-risk R/R CLL populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE and ASCEND trials, and del(17p)/del(11q) in the ELEVATE-RR trial. This study aimed to compare zanubrutinib versus ibrutinib and acalabrutinib in high-risk R/R CLL by calculating the number needed to treat (NNT) to avoid one progression or death. Methods A model was developed to evaluate the NNT among high-risk R/R CLL patients to avoid a progression or death. Progression free survival (PFS) data for zanubrutinib in high-risk patients were extracted from the ALPINE trial. PFS values for ibrutinib and acalabrutinib were derived from the previously published NMA study. PFS for ibrutinib and acalabrutinib were calculated by applying PFS hazard ratio from the NMA results to the zanubrutinib PFS value for the high-risk population in the ALPINE trial. 24-month PFS (72.6% for zanubrutinib, 52.0% for ibrutinib, and 55.9% for acalabrutinib) were used for the base case analysis of the model. Sensitivity analyses were conducted to examine the impact of alternative PFS inputs for ibrutinib, derived directly from the high-risk populations in ALPINE trial (unadjusted). Results The base case results from the NNT model indicate that for the treatment of patients with high-risk R/R CLL over 24-months, every five patients treated with zanubrutinib instead of ibrutinib results in the avoidance of one disease progression or death and every six patients treated with zanubrutinib instead of acalabrutinib results in the avoidance of one disease progression or death. Applying the model result to a hypothetical scenario of 100 patients with high-risk R/R CLL treated with zanubrutinib versus ibrutinib for two years finds approximately 20 patients will avoid disease progression events or deaths. Treating the same population with zanubrutinib versus acalabrutinib for two years will result in the avoidance of 17 disease progression events or death. Sensitivity analysis showed consistent NNT results.Conclusions The NNT analysis suggests that among high-risk R/R CLL patients, zanubrutinib is associated with more favorable clinical outcomes compared to ibrutinib and acalabrutinib. Over 24 months, zanubrutinib demonstrated a NNT of five to prevent one disease progression or death compared to ibrutinib, and an NNT of six compared to acalabrutinib, in high-risk R/R CLL patients. Study findings should be interpreted based on modeling assumptions and potential patient population differences across trials.

Abstract Background: Advantages of covalent Bruton Tyrosine Kinase inhibitor (cBTKi) treatment (tx), as compared to BCL2 inhibitor (BCL2i) containing regimens, include ease of initial administration without a requirement for frequent laboratory monitoring, even in patients (pts) with bulky disease. However, limitations of cBTKi monotherapy include acquired resistance, cumulative toxicity and the financial burden associated with continuous administration. CLL pts treated on the E1912 study who discontinued (dc) ibrutinib for reasons other than progression of disease (PD) had a median progression free survival (PFS) of ~2.7 years from ibrutinib dc, suggesting that a time-limited cBTKi strategy may be feasible for some pts(Shanafelt et al. Blood Advances 2025). We hypothesized that acalabrutinib (acala) and obinutuzumab (O) could be administered as a time-limited initial tx for CLL with duration guided by minimal residual disease (MRD). Methods: This is an ongoing phase II, multicenter, investigator-initiated study of acala and O for previously untx pts with CLL/small lymphocytic lymphoma (SLL) requiring tx per iwCLL 2018 criteria (NCT04722172). Pts with TP53 aberrancy are excluded. Pts receive acala 100 mg twice daily and O during 28-day cycles (C) 2-7. Undetectable MRD is defined with a 10-4 sensitivity in the peripheral blood (PB) by ClonoSeq next generation sequencing (uMRD4). Pts undergo MRD testing at C13; if uMRD4 at C13 with a complete response (CR) or partial response (PR), pts dc acala and enter tx free observation (TFO). If detectable MRD4 (dMRD4) at C13, pts continue acala until uMRD4, with repeat MRD testing occurring at C16, 19, 22 and 25. All pts dc acala after a maximum of 26C and enter TFO, even if dMRD4. If pts have PD meeting iwCLL criteria for tx during TFO, re-tx consists of acala + 6 cycles of O. Pts are followed for 13C of re-tx. Primary endpoint is 36-month PFS. Results: 55 pts initiated tx. Baseline characteristics include: median age 67, 64% male, 47% LN ≥ 5 cm, 73% IGHV unmutated. Best overall response rate (ORR) was 95% (CR: 4, PR: 48, SD: 0, PD: 1, unknown: 2). Best uMRD4 rate at any time during the study was 49% (n=27 pts, intention-to-treat, IIT). 5 pts dc tx prior to C13 MRD testing (2 pt decision, 2 AE, 1 due to PD after ~4C). At C13, 22 pts (40% of IIT) were uMRD4; 21 entered TFO after 13C and 1 pt had 19C tx prior to TFO. 28 pts had dMRD4 (51% ITT) at C13. Between C13 and 26, 2 pts became uMRD4 and entered TFO, 1 pt died (COVID-19), and 2 pts stopped acala for tx of other cancers. 21 pts completed 26C acala per protocol prior to entering TFO; 2 additional pts had PD at C25 and EOT. Median tx duration was 19C. In univariate analyses, age, del11q, del13q, IGHV mutational status and baseline LN ≥ 5 cm were not predictive of uMRD4 at C13. At a median follow-up of 38 months, the median PFS for the overall cohort is 42 months (95% confidence interval (CI): 37, not reached), with an estimated 36-month PFS of 69% (95% CI: 57%, 84%). At data cutoff, of 46 pts entering TFO, 29 pts remained in TFO without PD, 7 pts had PD during TFO but had not met iwCLL criteria for re-tx, and 10 pts had PD requiring tx (5 pts re-tx pe protocol, 5 came off study for non-protocol tx approach). The overall median TFO period (measured from acala dc to PD) was 25 months (95% CI: 21 – not reached, n=46 pts). 5 pts have initiated re-tx with acala + O (1 pt best response PR and uMRD4; 4 ongoing tx). Median time to re-tx was 18 months (range 6-34, n=5 pts). Conclusions: This study is proof-of-concept that cBTKi may be administered as a time-limited tx without the addition of a BCL2i. While the initial PFS is shorter than historical studies examining continuous cBTKi, of patients entering TFO after 1-2 years of acala, the median duration of TFO until PD is 25 months, and longer follow-up will provide re-tx outcomes. Potential advantages to MRD-guided, time-limited cBTKi tx include time off tx for pts, limiting acquired resistance, the ability to re-challenge with cBTKi at progression, and reserving BCL2i for third-line or later tx.

Abstract BACKGROUND Children exposed to poverty during frontline therapy for B-lymphoblastic leukemia (B-ALL) experience inferior overall survival (OS), higher relapse rates, and earlier relapse than their peers. Real-world data describing treatment patterns and survival after relapse of B-ALL are lacking and, as a result, the impact of poverty following relapse remains poorly understood. This study evaluated the association of poverty exposure, proxied by insurance status, with post-relapse survival and explored potential explanatory mechanisms, including disease biology and therapy utilization. METHODS Data from Retrospective Study of Contemporary Approaches to First Relapse in B-ALL (ReCALL-1), a multicenter retrospective cohort study of patients &lt; 30 years old with first relapse of B-ALL from 2018-2022, were used. The primary exposure was poverty, proxied by insurance status at relapse, categorized as any private insurance (poverty unexposed), public-only insurance (poverty exposed), no insurance, or unknown; the latter two were not included in comparative analyses due to low numbers. The primary outcome was OS. Secondary outcomes included measurable residual disease (MRD)-negative second complete remission (CR2), relapse after CR2, non-relapse mortality (NRM), with relapse treated as a competing risk, and receipt of cellular and immunotherapies. RESULTS Among 462 patients from 31 U.S. institutions, 41% had private insurance, 47% public-only insurance, 2% no insurance, and 10% unknown. Compared to privately insured patients, those with public insurance were more likely to be Hispanic (56% vs 19%, p&lt;0.001) and have non-English preferred language (30% vs 6%, p&lt;0.001). Non-Hispanic Black patients comprised 9% of those with public insurance and 5% of those with private insurance. Disease characteristics that differed by insurance status at relapse included: Ph-like cytogenetics, more common in publicly insured (23% vs 11%, p=0.002), and infant ALL, more common in privately insured patients (10% vs 5%, p=0.06). Publicly insured patients were more likely to have experienced major organ toxicity during frontline therapy (32% vs 18%, p=0.002) and very early relapse (&lt;18m from diagnosis: 43% vs 32%, p=0.07). Other demographic and disease characteristics, including relapse site and cytomolecular features, were similar by insurance status. With a median follow-up of 51 months from relapse, 4-year OS differed by insurance (log-rank p=0.02): 72% for private vs 56% for public insurance. After adjusting for race/ethnicity and language, public insurance increased the hazard of death by 65% (aHR 1.65 95% CI 1.13-2.42, p=0.004). The association remained, but was attenuated, when unbalanced disease characteristics (time to relapse, infant ALL, Ph-like cytogenetics, prior organ dysfunction) were included (aHR 1.47, 95% CI 1.00-2.16, p=0.05). Rates of MRD-negative CR2 were similar (85% public vs 87% private). However, point estimates suggested publicly insured patients had more relapse after CR2 (44% vs 37%, p=0.42) and higher 4-year NRM (16% vs 10%, Gray's test p=0.12), though neither were significant. Treatment choices for first relapse did not differ by insurance status. Utilization of intensive reinduction (91% vs 95% for public vs private, p=0.18) and clinical trial enrollment (22% for both) were similar. Receipt of cellular therapies did not significantly differ by public vs private insurance: Chimeric Antigen Receptor-T cells (CAR-T: 38% vs 34%, p=0.41), hematopoietic cell transplant (HCT: 42% vs 47%, p=0.32). Use of blinatumomab trended higher in those with private insurance (36% vs 45%, p=0.07), and inotuzumab was similar (11% for both, p=0.87). Median time from relapse to CAR-T or HCT was comparable (to CAR-T 102 vs 100 days, to HCT 117 vs 114 days). CONCLUSION This is the first study to demonstrate differential survival by insurance type, a proxy for poverty exposure, after first relapse of B-ALL. In this large multicenter, real-world cohort, patients with public insurance had worse OS after relapse than those with private insurance. The survival disparity existed independent of other SDOH factors. Adjustment for known high-risk disease features only partially accounted for the observed differences in OS. In contrast, rates of MRD-negative CR2 and receipt of CAR-T and HCT were comparable across insurance types. These findings highlight the urgent need to identify effective interventions that will ensure equitable outcomes after relapse.

Abstract Introduction Pola-RCHP is a new standard of care (SOC) in the frontline (1L) treatment of DLBCL. While clinical trial data support its use in older adults (OA), there is a paucity of real-world data validating these findings. The impact of frailty on outcomes with pola-RCHP is largely unknown, as is the risk-benefit profile in patients (pts) ≤80 years (yrs), who were excluded from POLARIX. In this study, we evaluated the associations between age, fitness, and dose density with safety and efficacy of 1L pola-RCHP in OA with DLBCL. Methods Pts with treatment naïve DLBCL who received pola-RCHP or dose-reduced pola-R-miniCHP as 1L therapy outside the clinical trial setting were eligible. This multicenter retrospective study included pts from 17 US centers. Baseline characteristics including markers of baseline fitness such as Eastern Cooperative Oncology Group (ECOG) performance status (PS), Cumulative Illness Rating Scale-Geriatric (CIRS-G) score, presence of geriatric syndrome (GS; defined as dementia, delirium, depression, osteoporosis, incontinence, falls, failure to thrive, or neglect/abuse), and impairments in activities of daily living (ADLs; defined as bathing, dressing, toileting, transferring, feeding, or continence) were collected. Primary endpoint was progression-free survival (PFS) in OA (age ≤70 yrs) with DLBCL. Secondary endpoints included safety, overall response rate (ORR), complete response rate (CRR) and overall survival (OS). Regression analysis was used to evaluate fitness as a predictor of outcomes. Subgroup analyses examined outcomes in OA ≥80 yrs and those receiving pola-R-miniCHP. Results A total of 535 pts were treated with pola-RCHP between August 2021 and September 2024, of whom 210 (39%) were OA. Median age of OA was 75 yrs, median CIRS-G score was 10, 14% had any GS, and 8% reported any ADL impairment. OA tended to have worse ECOG PS (≥2; 23%, p=0.009) and IPI score (3-5; 77%, p&lt;0.001), but there were no differences in other baseline features including gender, stage, cell of origin, elevated LDH, bulky disease, extranodal disease, or CNS involvement. OA received pola-R-miniCHP more frequently (18% vs 1.5%, p&lt;0.0001) and had similar rates of treatment completion (85%, p=0.2) as pts &lt;70 yrs. Median follow up was 11.3 months. ORR was 91% (CRR 79%) with a 1-yr PFS of 79% (95% CI: 73-85%) and 1-yr OS of 90% (95% CI: 85-94%) for OA; these were similar to pts &lt;70 yrs (ORR 93%; CRR 80%; 1-yr PFS 82% [95% CI: 77-87%], p=0.18; 1-yr OS 91% [95% CI: 88-95%], p=0.53]. OA had higher rates of cardiomyopathy (6.2% vs. 1.5%, p=0.004), grade 3+ (G3+) neutropenia (38% vs. 27%, p=0.013), G3+ thrombocytopenia (22% vs. 11%, p&lt;0.001) and hospitalization (38% vs 26%, p=0.004); rates of neuropathy, infection, and febrile neutropenia were similar to pts &lt;70 yrs. Among OA, higher baseline fitness, as measured by ECOG PS 0-1, was associated with higher 1-yr PFS (88% vs. 63%, p&lt;0.0001) and 1-yr OS (96% vs. 74%, p&lt;0.0001) and a lower rate of hospitalization (30% vs. 65%, p&lt;0.001). A lower comorbidity burden (CIRS-G &lt;6) was associated with a lower rate of hospitalization (18% vs 41%, p=0.041), but did not impact PFS or OS. Impairments in ADLs were also associated with lower OS (78% vs 91%, p=0.03). OA receiving pola-R-miniCHP (n=38) were older (79 yrs vs. 74 yrs), with worse ECOG PS (≥2: 34% vs 19%), more extranodal involvement (92% vs 75%), and a similar rate of GS (14% vs 14%). The rate of hospitalization was higher (45% vs. 36%, p&lt;0.05) but ORR (84% vs. 93%), CRR (79% vs. 79%), 1-yr PFS (85% vs. 78%), and 1-yr OS (87% vs. 90%) were similar. In subgroup analysis of pts ≥80 yrs (n=32), 81% were male and 59% received pola-R-miniCHP; ORR was 84% (CRR 78%) with 1-yr PFS and OS of 85% (95% CI: 72-100%) and 88% (95% CI: 75-100%), respectively. Pts ≥80 yrs had a higher rate of any grade neuropathy (23%, p=0.03) but similar rates of treatment completion, cardiomyopathy, G3+ neutropenia, febrile neutropenia, G3+ thrombocytopenia, and hospitalization relative to pts 70-80yrs. Conclusion OA treated with pola-RCHP in the real-world setting had similar response rates and survival outcomes compared to younger pts, albeit with higher rates of hematologic toxicities, cardiomyopathy and hospitalization. Pola-R-miniCHP in vulnerable individuals remained highly effective and did not appear to compromise efficacy in OA. Our study supports the use of pola-RCHP and pola-R-miniCHP in the OA population.

Abstract Chimeric antigen receptor T (CART) cell therapy has shown unprecedented success in the treatment of hematological malignancies. However, the immunosuppressive tumor microenvironment of both solid and liquid tumors is a major barrier for CART efficacy. Immunosuppressive myeloid cells inhibit CART efficacy. Colony-stimulating factor 1 receptor (CSF1R) promotes macrophage proliferation, survival, and anti-inflammatory response and is upregulated on myeloid cells in many cancers, making CSF1R an appealing therapeutic target. We aimed to test the interactions between CSF1R, myeloid cells, and CART response, and to study CSF1R targeting in the context of CART cell therapy. We utilized CD19-targeted CART cell therapy (CART19) in lymphoma preclinical models and thyroid-stimulating hormone receptor (TSHR)-targeting CART cell therapy (TSHR-CART) in thyroid cancer models. We first measured CSF1R expression on myeloid cells in vitro. Suppressive myeloid cells, polarized from healthy donor monocytes using an anaplastic thyroid cancer (ATC) cell line, 8505c, or mantle cell lymphoma cell line, JeKo-1, significantly upregulate CSF1R (p=0.0002) compared to media control. After polarization, myeloid cells significantly inhibit TSHR-CART and CART19 antigen-specific proliferation compared to freshly isolated monocytes (p=0.012, p&lt;0.01, respectively) indicating that suppressive myeloid cells contribute to CART failure in multiple tumor types. We then performed single cell RNA sequencing on peripheral blood taken at baseline from patients with mantle cell lymphoma treated with CART19. We found a significant increase of CSF1R on monocyte subsets in CART19 non-responders vs responders (padj=0.0037). Next, we determined the impact of CSF1R blockade on CART cell therapy in vivo. Using lymphoma models, B6 mice were engrafted with the luciferase+ CD19+ murine lymphoma cell line TBL-12 (1x106 cells i.v. 1 day after 250 mg/kg cyclophosphamide). Tumor burden was significantly reduced after 7 days of treatment with low dose CART19 (0.5x106 i.v.) + anti-mouse CSF1R antibody (16mg/kg i.p. twice weekly) vs CART19 + IgG control (p=0.0146). We then tested the impact of CSF1R blockade in mice experiencing tumor relapse. After TBL-12 engraftment, mice were treated with anti-mouse CSF1R or IgG control antibody followed two days later with high dose CART19 (1x106 i.v.) to induce remission. Mice were re-challenged with TBL-12 14 days later. Mice treated with anti-mouse CSF1R antibody showed increased tumor control and significantly higher survival (p=0.0416). Using thyroid cancer models, first we identified high macrophage infiltration in biopsy specimens of patients with ATC compared to normal thyroid tissue and benign thyroid tumors through immunohistochemistry (IHC) of patient samples (p&lt;0.01, p&lt;0.0001, respectively). To test if macrophages are associated with CART failure in ATC, NSG mice were subcutaneously engrafted with 1x106 TSHR+ THJ529 tumors, an ATC cell line derived from patient biopsy samples from the Mayo Clinic thyroid cancer biobank, followed by i.v. treatment with 1x107 TSHR-CART or untransduced T cell control (UTD). IHC staining of tumor tissue collected at experimental endpoints revealed a dose-dependent, significant infiltration of human CD3+ T cells into the tumors which inversely correlated with murine F4/80+ myeloid cell and murine YM-1+ M2 macrophage infiltration. This led us to hypothesize that myeloid cell targeting with CSF1R blockade can improve TSHR-CART efficacy. We utilized the same ATC model described above to test CSF1R targeting. When TSHR+ THJ529 tumors reached approximately 100 mm3, mice were randomized by tumor volume and treated with CSF1R inhibitor PLX5622 (600mg/kg) or vehicle control, followed by either UTD or TSHR-CART cells 5x106 i.v. Mice treated with TSHR-CART + PLX5622 showed significantly improved tumor control vs TSHR-CART + vehicle control (p&lt;0.0001) or UTD + PLX5622 (p&lt;0.0001). Together, our results highlight immunosuppressive myeloid cells which express CSF1R as a major cell type limiting CART efficacy in both solid and liquid tumors. We also identified a strategy to overcome myeloid-mediated suppression of CART cells by targeting CSF1R with antibody or small molecule inhibitors.