Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

Current and future therapies for follicular lymphoma.

Follicular lymphoma (FL) is an indolent, germinal center B cell-derived lymphoid neoplasm, for which recent advances in treatment have substantially improved patient survival. However, FL remains an incurable and heterogeneous disease, with groups of patients experiencing early disease progression, histologic transformation, or a high risk of treatment-related toxicity. Additionally, FL is a continually relapsing disease, and response rates and disease-control intervals decrease with each subsequent line of therapy. In this review, we explore the current treatment landscape for relapsed or refractory FL and promising therapies in development, highlighting the efficacy and potential risks of each treatment. We provide a real-world perspective on the unmet needs of patients with FL. Novel therapeutic approaches in development offer a wide array of options for clinicians when treating relapsed or refractory FL. A nuanced approach is required to address the needs of individual patients, taking into consideration both the risks and benefits of each treatment option, as well as patient preferences.

Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Outcomes of r/r B-cell NHL patients with limited (<5 Sites) pre-CART Disease Bridged With or Without Radiotherapy.

Unirradiated relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) patients who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized pre-CART disease. This study reports on the outcomes of r/r NHL patients with limited (<5 involved sites) disease bridged with or without radiotherapy (BRT). A multi-center retrospective review of 150 patients with r/r NHL who received CART with <5 disease sites prior to leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study endpoints included relapse free-survival (RFS), event-free survival (EFS) and overall survival (OS). Prior to CART infusion, 48 (32%) patients received BRT and 102 (68%) did not. The median follow-up was 21 months. Following CART infusion, BRT patients had higher objective response (92% vs 78%, p=0.046) and sustained complete response (54% vs 33%, p=0.015) rates. Local relapse in sites present prior to CART was lower in the BRT group (21% vs. 46%, p=0.003). BRT patients had improved 2-year RFS (53% vs 44%, p=0.023) and 2-year EFS (37% vs 34%, p=0.039) compared to no BRT patients. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared to 42% in those who did not (p=0.002). BRT prior to CART for patients with limited (<5 involved disease sites) r/r NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.

Impact of the COVID-19 pandemic on mechanical ventilation cases and mortality rates in non-SARS-CoV-2 patients: A nationwide analysis in Spain.

BACKGROUND: The COVID-19 pandemic has presented unprecedented challenges for healthcare systems globally, impacting critical care resources and patient outcomes. Understanding its multifaceted effects is crucial for future crisis response. OBJECTIVE: Analyze the repercussions of the COVID-19 pandemic on mechanical ventilation cases and mortality among non-SARS-CoV-2 patients. METHODS: A nationwide database encompassing all patients receiving mechanical ventilation in Spain was used to compare the number of cases and clinical outcomes during COVID-19 (March 2020 - December 2021) to pre-pandemic cases (May 2018 - February 2020). Univariate and multivariate analyses were employed. RESULTS: COVID-19 significantly reduced access to ventilation for non-COVID-19 patients. A 16 % decrease (12,099 fewer patients) was observed during the pandemic compared to pre-pandemic times. This reduction affected all analyzed conditions except self-inflicted injuries, coinciding with a rise in overall mortality risk (34.5% vs 35.6 %, OR 1.09, 95 %CI 1.06-1.12). The increased mortality was consistent across diverse admission types, including cancer (37.1% vs. 41.5 %, OR 1.18, 95 %CI 1.09-1.29), hemorrhagic strokes (55.4% vs. 56.6 %, OR 1.07, 95 %CI 1.02-1.20), acute myocardial infarction (35.6% vs. 38 %, OR 1.11, 95 %CI 1.01-1.21), non-SARS-CoV-2 pneumonia (44.5% vs. 45.8 %, OR 1.12, 95 %CI 1.02-1.24), septic shock (54.7% vs. 56.3 %, OR 1.10, 95 %CI 1.06-1.15), and prolonged ventilation (≥96 h) (37% vs. 38.2 %, OR 1.10, 95 %CI 1.06-1.10). CONCLUSIONS: The findings underscore the profound impact of the COVID-19 pandemic on critical care utilization and patient outcomes among non-SARS-CoV-2 patients. As healthcare systems strive to mitigate future crises, these insights emphasize adaptable strategies for equitable access to life-saving treatments.

Epigenetic-based differentiation therapy for Acute Myeloid Leukemia.

Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.

FdeC expression regulates motility and adhesion of the avian pathogenic Escherichia coli strain IMT5155.

Adaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.

Images in Immunotherapy and Precision Oncology: A Case Report of Neurofibromatosis-1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that primarily causes the growth of tumors along nerves. Additionally, the germline mutations involved in NF1 predispose patients to develop further malignancies. The mainstay initial treatment for these malignancies is surgical removal at diagnosis, although targeted therapies are under evaluation in the relapsed setting. We report a case of malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor (GIST), and pheochromocytoma in a patient with NF1 who presented with an infected right shoulder lesion that was confirmed to be spindle cell sarcoma via biopsy. She was treated with antibiotics; however, she rapidly deteriorated and opted for hospice care. NF1 germline mutations increase the risk of patients developing various types of cancer. Recent studies have shown that there is a role for using MEK inhibitors such as selumetinib for treating patients with NF1.

Comprehensive Bridging Radiotherapy for Limited Pre-CART Non-Hodgkin Lymphoma.

This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.

A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation.

Mouse embryonic stem cells (mESCs) in the primed pluripotency state, which resembles the post-implantation epiblast, can be de-differentiated in culture to a naive state that resembles the pre-implantation inner cell mass. We report that primed-to-naive mESC transition entails a significant slowdown of DNA replication forks and the compensatory activation of dormant origins. Using isolation of proteins on nascent DNA coupled to mass spectrometry, we identify key changes in replisome composition that are responsible for these effects. Naive mESC forks are enriched in MRE11 nuclease and other DNA repair proteins. MRE11 is recruited to newly synthesized DNA in response to transcription-replication conflicts, and its inhibition or genetic downregulation in naive mESCs is sufficient to restore the fork rate of primed cells. Transcriptomic analyses indicate that MRE11 exonuclease activity is required for the complete primed-to-naive mESC transition, demonstrating a direct link between DNA replication dynamics and the mESC de-differentiation process.

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity.

ABSTRACT: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.

Effect of an immune challenge and two feed supplements on broiler chicken individual breast muscle protein synthesis rate.

Optimization of broiler chicken breast muscle protein accretion is key for the efficient production of poultry meat, whose demand is steadily increasing. In a context where antimicrobial growth promoters use is being restricted, it is important to find alternatives as well as to characterize the effect of immunological stress on broiler chicken's growth. Despite its importance, research on broiler chicken muscle protein dynamics has mostly been limited to the study of mixed protein turnover. The present study aims to characterize the effect of a bacterial challenge and the feed supplementation of citrus and cucumber extracts on broiler chicken individual breast muscle proteins fractional synthesis rates (FSR) using a recently developed dynamic proteomics pipeline. Twenty-one day-old broiler chickens were administered a single 2H2O dose before being culled at different timepoints. A total of 60 breast muscle protein extracts from five experimental groups (Unchallenged, Challenged, Control Diet, Diet 1 and Diet 2) were analysed using a DDA proteomics approach. Proteomics data was filtered in order to reliably calculate multiple proteins FSR making use of a newly developed bioinformatics pipeline. Broiler breast muscle proteins FSR uniformly decreased following a bacterial challenge, this change was judged significant for 15 individual proteins, the two major functional clusters identified as well as for mixed breast muscle protein. Citrus or cucumber extract feed supplementation did not show any effect on the breast muscle protein FSR of immunologically challenged broilers. The present study has identified potential predictive markers of breast muscle growth and provided new information on broiler chicken breast muscle protein synthesis which could be essential for improving the efficiency of broiler chicken meat production. SIGNIFICANCE: The present study constitutes the first dynamic proteomics study conducted in a farm animal species which has characterized FSR in a large number of proteins, establishing a precedent for biomarker discovery and assessment of health and growth status. Moreover, it has been evidenced that the decrease in broiler chicken breast muscle protein following an immune challenge is a coordinated event which seems to be the main cause of the decreased growth observed in these animals.

Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.

The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/ß-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program.

Navigating between Scylla and Charybdis: A roadmap to do better than Pola-RCHP in DLBCL.

In treating diffuse large B-cell lymphoma (DLBCL), oncologists have traditionally relied on the chemotherapy backbone of R-CHOP as standard of care. The two dangers that the hematologist must navigate between are the aggressive disease (Charybdis that in the absence of therapy systematically destroys all the ships) and the toxicity of the therapies (Scylla with its six monstrous heads that devours six crew members at a time), and hematologists have to navigate very carefully between both. Therefore, three different strategies were employed with the goal of improving cure rates: de-escalating regimens, escalating regimens, and replacement strategies. With a replacement strategy, a breakthrough in treatment was identified with polatuzumab vedotin (anti-CD79B antibody/drug conjugate) plus R-CHP. However, this regimen still did not achieve the elusive universal cure rate. Fortunately, advances in genomic and molecular technologies have allowed for an improved understanding of the heterogenous molecular nature of the disease to help develop and guide more targeted, precise, and individualized therapies. Additionally, new pharmaceutical technologies have led to the development of novel cellular therapies, such as chimeric antigen receptor (CAR) T-cell therapy, that could be more effective, while maintaining an acceptable safety profile. Thus, we aim to highlight the challenges of DLBCL therapy as well as the need to address therapeutic regimens eventually no longer tethered to a chemotherapy backbone. In the intersection of artificial intelligence and multi-omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics), we propose the need to analyze multidimensional biologic datato launch a decisive attack against DLBCL in a targeted and individualized fashion.

Outcomes of subsequent antilymphoma therapies after second-line axicabtagene ciloleucel or standard of care in ZUMA-7.

ABSTRACT: The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = 59) was 6.3 vs 1.9 months, respectively; median OS was 16.3 vs 9.5 months, respectively. In the axi-cel arm, 84 of 180 randomized patients (47%) received 3L therapy. Median PFS among those who received 3L chemotherapy (n = 60) vs cellular immunotherapy (n = 8) was 1.7 vs 3.5 months, respectively; median OS was 8.1 months vs not reached, respectively. Of the 60 patients who received 3L chemotherapy, 10 underwent stem cell transplantation (SCT) after salvage chemotherapy. Median PFS was 11.5 vs 1.6 months, and median OS was 17.5 vs 7.2 months for those who did vs did not reach SCT, respectively. Eight patients received 3L cellular immunotherapy after 2L axi-cel. Of these, 6 patients received subsequent SCT in any line; all 6 were alive at data cutoff. These findings help inform subsequent treatment choices after 2L therapy failure for relapsed/refractory LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

Applying the EHA/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality.

ABSTRACT: Cytopenias represent the most common side effect of CAR T-cell therapy (CAR-T) and can predispose for severe infectious complications. Current grading systems, such as the Common Terminology Criteria for Adverse Events (CTCAE), neither reflect the unique quality of post-CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter, observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR-T for refractory B-cell malignancies (112 multiple myeloma [MM], 334 large B-cell lymphoma [LBCL], 103 mantle cell lymphoma [MCL]) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r = 0.92, P < .0001), the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in patients with MCL vs those with LBCL and MM (28% vs 23% vs 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs 13%, P < .0001), increased nonrelapse mortality (14% vs 4%, P < .0001), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%, both P < .0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared with the CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies.

Long-term outcomes of patients with large B-cell lymphoma treated with axicabtagene ciloleucel and prophylactic corticosteroids.

ZUMA-1 safety management cohort 6 investigated the impact of prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab on the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs) following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Prior analyses of cohort 6 with limited follow-up demonstrated no Grade ≥3 CRS, a low rate of NEs, and high response rates, without negatively impacting axi-cel pharmacokinetics. Herein, long-term outcomes of cohort 6 (N = 40) are reported (median follow-up, 26.9 months). Since the 1-year analysis (Oluwole, et al. Blood. 2022;138[suppl 1]:2832), no new CRS was reported. Two new NEs occurred in two patients (Grade 2 dementia unrelated to axi-cel; Grade 5 axi-cel-related leukoencephalopathy). Six new infections and eight deaths (five progressive disease; one leukoencephalopathy; two COVID-19) occurred. Objective and complete response rates remained at 95% and 80%, respectively. Median duration of response and progression-free survival were reached at 25.9 and 26.8 months, respectively. Median overall survival has not yet been reached. Eighteen patients (45%) remained in ongoing response at data cutoff. With ≥2 years of follow-up, prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab continued to demonstrate CRS improvement without compromising efficacy outcomes, which remained high and durable.

Histiocytic Sarcoma Treated with Pembrolizumab: A Case Report and Literature Review.

Histiocytic sarcoma (HS) is a rare hematologic malignancy that has historically been treated with lymphoma-based regimens with a median survival of 6 months. We describe a case of a 51-year-old woman who presented with acute back pain and cord compression. She was diagnosed with HS with diffuse skeletal lesions and high expression of programmed death ligand 1 (PD-L1). She was subsequently treated with chemotherapy plus off-label use of pembrolizumab followed by allogeneic stem cell transplantation. Ultimately, the patient died in the setting of progression of disease 17 months after her stem cell transplantation and 26 months after her diagnosis. This article also presents a literature review of cases of HS treated with programmed death ligand inhibition.