Edwards Comprehensive Cancer Center

340 Background: Gastric cancer is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide, with a 5-year survival rate of ~32%. Sepsis substantially worsens outcomes in cancer patients, increasing mortality risk by 3–5 fold. While palliative care is recommended to improve quality of life and align goals of care, its role in gastric cancer patients admitted with sepsis is not well defined. Methods: We conducted a retrospective cross-sectional study using the 2018–2021 National Inpatient Sample. Hospitalized Adults with gastric cancer and coexisting sepsis were identified using ICD-10 codes. The exposure was receipt of a palliative care consult. The primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), respiratory failure, mechanical ventilation, shock, length of stay (LOS), and hospitalization charges. Survey-weighted descriptive statistics and multivariable regression analyses adjusted for possible confounders. Results: Among 12,750 weighted hospitalizations for gastric cancer with sepsis, 29.6% received a palliative care consult. In-hospital mortality was higher in the palliative group compared to non-palliative (40.3% vs 22.2%), with palliative care significantly associated with nearly four-fold greater odds of death (OR 3.89, 95% CI 3.18–4.75, p <0.001). Palliative care was also associated with increased risk of acute kidney injury (OR 1.61, 95% CI 1.36–1.91, p <0.001), respiratory failure (OR 1.90, 95% CI 1.58–2.28, p <0.001), mechanical ventilation (OR 1.37, 95% CI 1.03–1.83, p =0.033), and shock (OR 1.84, 95% CI 1.54–2.21, p <0.001). There were no significant differences in length of stay (8.0 vs 8.0 days, p =0.59) or hospitalization charges ($108,795 vs $106,258, p =0.93) between groups. Conclusions: In this nationwide analysis, palliative care consultations in gastric cancer patients with sepsis were associated with higher in-hospital mortality and greater odds of acute complications. These findings likely reflect the fact that palliative care is often initiated later in the hospital course, when patients are already severely ill and stabilization efforts are underway. Consequently, the observed associations may be more indicative of delayed initiation rather than a direct effect of palliative care itself. Future studies should specifically evaluate the timing of palliative involvement- early versus late initiation- to better understand its impact on outcomes in this high-risk population.

e12542 Background: Early stage (Stage I-III) human epidermal receptor -2 (HER2) positive and triple negative breast cancers (TNBC) tend to behave more aggressively than hormone positive breast cancers with higher and earlier incidences of recurrences. Oftentimes, testing for receptor subtypes is done only on the primary tumor and not on the synchronous axillary metastasis, with the assumption that the axillary metastasis is congruous to the primary lesion. Current guidelines also do not specify a requisite to do this testing. Information about the receptor expression types is fundamental for the treatment of breast cancer. We aimed to determine if there is significant discordance between the primary and ipsilateral axillary metastasis in early-stage breast cancer. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. Sample for this study included all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Data on demographics, comorbidities, receptor status, staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 140 patients had axillary node positive disease. 40 (29%) of the 140 patients underwent testing for receptors subtypes on both primary and axillary nodal metastasis. 8 (20%) of the 40 patients had discordance in their receptor subtype expressed in their respective axillary nodal metastasis. 32 (80%) of the 40 patients had axillary receptor expression congruous to the primary tumor. At the time of our review, there was no statistically significant mortality between discordant compared to concordant group (13% vs 20%; p=0.54). 2 patients were lost to follow up. Conclusions: Our data suggests that one in every five axillary metastatic breast cancers can have receptor subtypes discordant compared to the receptors expressed on the primary tumor. Knowledge about any such discordance between the primary and respective axillary metastasis has a consequential impact on the treatment approach for early-stage breast cancer. This is especially true if the patient’s nodal metastatic lesions indeed prove HER2 receptor positivity or do not express any receptors (TNBC). Consequently, patients may be being deprived of benefits from advances in treatment of these cancers, such as targeted therapies towards HER2 receptor, hormonal treatments when indicated, or the utilization of neoadjuvant chemotherapy. A strong case can be thus made to revise current standards to include receptor testing on all primary and synchronous axillary metastasis. Further testing is needed to validate our findings.

We present a rare case of erythrocytosis due to a homozygous SLC30A10 mutation, causative of Hypermanganesemia with Dystonia, Polycythemia, and Cirrhosis (HMDPC). The patient presented at 7 years of age with the incidental finding of hemoglobin up to 22.3 g/dL. Despite extensive phenotypic evaluation and genetic testing for common causes of erythrocytosis, etiology remained unknown for 1.5 years until whole exome sequencing revealed the genetic diagnosis. Upon neurological evaluation, the patient was found to have very mild dystonia due to manganese deposition in the basal ganglia, midbrain, and cerebellum, as seen in brain MRI. Chelation with trientine orally was initiated, which led to resolution of his erythrocytosis along with decrease of Mn deposition in brain tissues. Recurrence of erythrocytosis occurred after 4 years due to inappropriately stored trientine and iron deficiency. This required the temporary addition of intravenous calcium disodium edetate to his treatment regimen. This case illustrates the development of secondary erythrocytosis due to hypermanganesemia leading to manganese deposition in the hepatocytes, causing a sense of tissue hypoxia and stimulating erythropoietin production. It also shows the competition between manganese and iron for absorption in the body. Moreover, it demonstrates the importance of broad genetic evaluation for the diagnosis of ultra-rare diseases. In this case, timely diagnosis and initiation of appropriate treatment prevented irreversible damage to the brain and liver with a profound improvement on his prognosis.

Hemophagocytic Lymphohistiocytosis, also known as HLH, is a group of disorders classified as a type of cytokine release syndrome triggering an abnormal activation of lymphocytes. First described in a pediatric case with viral trigger in 1979, the key features of this syndrome include rapid progression with high mortality and impaired immunity. Many different etiological triggers have been described since the initial case. The syndrome can have profound impacts on all body systems which is explored to some extent within this text. Several agents have been tried in the treatment of this condition, particularly with respect to sustained remission and mortality benefits overall. This review seeks to outline clinical presentation and prognostic factors of HLH as well as recent advances in clinical treatment. Trials are discussed from literature review outlining prognostic markers as well as a discussion of tried therapies, recent advances and emerging agents of interest. Significant progress has been made in recent years although this remains a very complex and challenging disease to treat and mortality also remains high.

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: To reduce AML relapse post-HCT, a CD33 CRISPR/Cas9 gene-edited donor allograft, tremtelectogene empogeditemcel (trem-cel, formerly VOR33), was developed to enable post-HCT CD33-directed therapies while protecting healthy donor cells from on-target myelosuppression. Aims: VBP101 (NCT04849910) is a Phase 1/2a trial designed to evaluate the safety of trem-cel and GO (Mylotarg™), an anti-CD33 antibody-drug conjugate, in AML patients who are at a high risk of relapse post-HCT. Methods: Patients with CD33+ AML and prognostic factors for high risk of relapse post-HCT underwent myeloablative busulfan/melphalan/fludarabine/ATG conditioning followed by HCT with trem-cel. Trem-cel was manufactured from G-CSF + plerixafor-mobilized cells from HLA-matched (10/10) unrelated donors. As part of the trial’s initial dose escalation, patients are treated with up to four 28-day cycles of GO, with cohort 1 starting at 0.5 mg/m2 on the first day of each cycle, beginning at ~60 days post-HCT with trem-cel. Results: To date, three patients underwent HCT with trem-cel and received cell doses between 3 and 8 x 106 CD34+ cells/kg with 80% to 88% CD33 deletion. For all three patients, neutrophil engraftment occurred on days 10–11 (Fig. 1a). Patient 1 showed 100% donor chimerism in whole blood and myeloid cells at D28 up to the end of the study (D147). At the D28 assessment, 95% of neutrophils and 94% of monocytes in peripheral blood (PB) were CD33 negative. Similarly, bone marrow (BM) analysis showed 95% of maturing myeloid cells, 92% of maturing monocytes and 94% of CD34+ myeloblasts were CD33 negative with development patterns comparable to a reference non-edited post-HCT BM. Similar levels of CD33 negativity were observed at the D28 assessment in the PB and BM of patient 2. Patient 1 was treated with a single infusion of 0.5 mg/m2 of GO at each of the 28-day cycles for a total of 3 cycles. PK analysis during the first cycle of GO demonstrated a Cmax of 259 ng/mL and AUCinf of 22924 ng/mL*hr, which was comparable to doses of 1–2 mg/m2 and 4–5 mg/m2, respectively in AML patients, exposures predicted to cause cytopenias. CD33-negative donor myeloid hematopoiesis was enriched from 96% to 99.9% following the first dose of GO. This enrichment was reflected at a genetic level, where enrichment of CD33 deletion was observed in both myeloid and lymphoid lineages following the first dose of GO. No significant decrease in neutrophil or platelet counts was observed through the 3 cycles of GO treatment for up to D147 (Fig 1b). Patients 2 & 3 are scheduled to begin GO treatment after D+60. No trem-cel-related adverse events were reported in any of the 3 patients. There was no incidence of elevations in liver function tests after GO or other GO-related SAEs. Summary/Conclusion: CD33-edited allogeneic donor cells were successfully engrafted, with neutrophil engraftment similar to patients who received non-edited CD34-selected grafts (Luznik et al 2022, JCO 40:356-368). Consistent with high CD33 editing efficiency in trem-cel, the majority of PB and BM myeloid cells lacked CD33 expression. The CD33 deletion was detected across donor cells of myeloid and lymphoid lineages, suggesting successful editing of a multipotent progenitor. In the context of a CD33-deleted graft, PK of a 0.5mg/m2 dose of GO demonstrated a higher Cmax and AUC than previously reported in AML patients. No cytopenias were observed after treatment with GO, supporting the hypothesis that CD33 deletion can protect donor cells from GO-mediated toxicity. These initial data support the biologic dispensability of CD33 and a potential approach enabling post-HCT treatment with GO and other CD33-targeted therapies while avoiding typical on-target myelosuppressive toxicity.Keywords: Gemtuzumab ozogamicin, Gene therapy, AML, Allogeneic bone marrow transplant

Since gaining FDA approval in 2014, pembrolizumab, a PD-1 immune checkpoint inhibitor, has been utilized in the management of cancers that progress following first-line therapy.While the pathological response to pembrolizumab is favorable, immune related adverse events (irAEs) can be elicited and require prompt diagnosis and management based on grading and severity, which can include discontinuation of immunotherapy.Our case concerns a 66-year-old female with recurrent endometrial cancer who was treated with pembrolizumab, and developed inflammatory arthritis following therapy. We provide a succinct review of the pathogenesis and risk factors associated with irAEs, as well as diagnosis and management strategies.

Metaplastic breast cancer (MBC) in men is an extremely rare entity. MBC is typically very aggressive with a poor prognosis. In men, it has only been reported three times in the literature. We report a 47-year-old man who presented with right-sided breast erythema and nipple inversion. Mammogram revealed a 2.4 cm spiculated mass. Initial pathology was inconclusive; however, right-sided simple mastectomy showed invasive metaplastic carcinoma with adenosquamous histology. He received adjuvant chemotherapy with 4 cycles of dose dense Adriamycin and cyclophosphamide followed by 12 weeks of paclitaxel and chest wall radiation. Although oestrogen receptor status was 1%, tamoxifen was not given due to recent diagnosis of pulmonary embolism. Two years after treatment, he is currently living with no signs of recurrence. This case will serve as a useful addition to the current literature discussing successful diagnosis, treatment and prognosis of a man with MBC.

A 73-year-old woman with hepatocellular carcinoma localised to the liver was treated with doxorubicin-loaded drug-eluting beads through transcatheter arterial chemoembolisation (DEB-TACE). She developed subcutaneous, erythematous, tender nodules in her abdomen 3 days after the procedure. PET/CT scan that was done to evaluate for evidence of disease progression showed mild avidity of these nodules. Biopsy showed fatty necrosis. Nodules started to improve spontaneously 2 weeks after onset. At 8 weeks after onset, lesions stabilised in size and the associated tenderness and erythema resolved. This represents a rare side effect of TACE procedure in general. It can happen secondary to non-target embolisation of hepatic falciform artery, planned embolisation of extrahepatic collateral supplies and even when there is no clear cause. Spontaneous resolution of acute symptoms usually occurs over the course of few weeks, though subcutaneous lesions consisting of necrotic fat tissue may persist for longer periods.