Mosalem, Osama

220 Background: There is a critical need to identify biomarkers of response and resistance to 177Lu-PSMA-617. Post-hoc analyses of VISION have explored the prognostic and predictive value of select clinical parameters. However, we are still in the early stages of deciphering which molecular changes are associated with favorable or adverse treatment outcomes. Methods: We conducted a retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC), who received 177Lu-PSMA-617 at Mayo Clinic in Rochester, Minnesota, in the interval of March 2022 to March 2023. We included patients who provided research authorization, had a baseline PSA of at least 2 ng/mL, received at least 2 cycles of treatment, and had circulating tumor DNA (ctDNA) genomic profiling performed by Guardant (83 gene panel) within 60 days of treatment initiation. Clinical, laboratory, genomic, and radiomic parameters were abstracted by trained research personnel. Two independent analyses of “response” and “resistance” were performed. Response to treatment was defined as 50% or greater decrease in PSA from baseline (PSA50 response: dichotomized yes versus no), and resistance was defined as non-decreasing or rising PSA during treatment (PSA non-response: dichotomized yes versus no). Associations between gene alterations and response and resistance were evaluated via Fisher’s exact tests. Results: Between March 2022 and March 2023, 273 patients received cycle 1 of 177Lu-PSMA-617. A total of 108 patients met the inclusion criteria. The median number of cycles at data cutoff was 6 (IQR: 4,6) with 57 (53%) patients receiving all 6 planned cycles. The median PSA at baseline was 16.65 ng/ml (IQR: 5.20, 66.12). A total of 65 patients (60%) experienced a PSA50 response. No molecular alterations were associated with a higher rate of PSA50 response; however, alterations in ARID1A, AR, and CHEK2 were associated with lack of PSA50 response (Fisher’s exact p < 0.05). Of the 108 evaluable patients, 20 (19%) met criteria for PSA non-response. Alterations in AR, ARID1A, MYC, TP53, CHEK2, ATM, EGFR, and NOTCH1 were significantly associated with PSA non-response (Fisher’s exact p < 0.05); in each case, the presence of the alteration was positively associated with resistance (i.e., more instance of PSA non-response). No biomarkers were found to be inversely associated with PSA non-response. Conclusions: ctDNA assessed by commercially available, targeted sequencing panels prior to treatment may be useful in identifying the patients least likely to benefit from 177Lu-PSMA-617. Further work is ongoing to integrate ctDNA findings with clinical parameters in the hopes of understanding the factors mediating response and resistance to therapy.

175 Background: It is well-known that patients with liver metastases from metastatic castration resistant prostate cancer (mCRPC) have poorer or transient responses to many forms of systemic therapy. Data on outcomes following treatment with Lutetium-177–PSMA-617 is scarce. The VISION trial reports hazard ratios for overall survival in the subgroup of patients with liver metastases without disclosing the absolute duration of survival. Using real-world clinical data, we examine this important subgroup of patients, describing their PSA response rates and survival. Methods: A single institution database was assembled to include all patients receiving 177-Lu-PSMA-617 at Mayo Clinic Rochester, MN, and starting treatment in the interval of March 2022 to March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were categorized based on the presence or absence of measurable liver metastases on their baseline PSMA PET scan. Best PSA response while on treatment was annotated and reported as percent decline from baseline. Survival was calculated from date of first cycle of 177-Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (liver metastases versus no liver metastases) were compared using Chi square test and Kaplan-Meier method, respectively. Those with available pre-treatment circulating tumor DNA (ctDNA) genomic profiling, performed by Guardant (83 gene panel), were assessed for the presence of pathogenic and likely pathogenic alterations. Findings are summarized using descriptive statistics. Results: The overall cohort consisted of 212 patients, including 29 (14%) with liver metastases on pre-treatment PSMA PET/CT. The median number of cycles received was 4 (range, 1-6) for patients with liver metastases and 6 (range, 1-6) for those without hepatic involvement. The observed PSA50 response trended lower for those with liver metastases (34.5% [10/29] versus 51% [94/183], p= 0.091). At median (IQR) follow-up of 10 (8-12) months, there was a numerical but not statistically significant difference in median OS (11.28 months versus NR, p=0.066). In the exploratory analysis of baseline ctDNA, BRCA2 copy number loss was relatively enriched among patients with liver metastases (4 of 19, 21%) versus patients without liver disease (5.7%, 9/158). Conclusions: Our data suggest that the presence of liver metastases predict poorer outcomes in patients receiving Lutetium-177–PSMA-617 treatment, which is similar to data reported with other forms of systemic therapy for mCRPC. To maximize the anti-tumor activity of radioligand therapy in the liver, combination approaches should be explored.

592 Background: The introduction of peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) DOTATATE has led to a paradigm shift in the treatment of neuroendocrine tumors (NETs). Hematological toxicity is a well-recognized adverse effect (AE) of 177Lu DOTATATE. Most cytopenias are transient, with an estimated incidence of 10-25%, typically mild to moderate in severity (grade G1-2). The most dreaded AE of PRRT is therapy-related myeloid neoplasm (t-MN), with an estimated 2-8% incidence and a higher incidence reported in patients who also received prior chemotherapy. We sought to evaluate the hematological safety of 177Lu PRRT in the setting of NETs with extensive (i.e., innumerable) bone metastases. Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as >50% skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with 177Lu DOTATATE. Pts characteristics and laboratory results were collected before, during, and after 177Lu DOTATATE treatment. Hematotoxicity was graded according to the NCI-CTCAE v5. Results: Out of 27 pts, 13(48%) developed cytopenia(s) of any grade after treatment with one or more cycles of 177Lu DOTATATE. In total, there were 13(48%) pts with anemia, 13(48%) with thrombocytopenia, and 6(22%) with neutropenia. Six (22%) pts had severe hematological toxicity (G3-4). Twelve months post-PRRT, 7(26%) pts continued to experience cytopenia(s) of any grade, of whom 4(15%) had G3-4 hematotoxicity. One pt developed t-MN, and two pts had myelophthisis on bone marrow biopsy from infiltrating NET. 16(59%) pts received cytotoxic chemotherapy before PRRT, and 7(25.9%) developed subsequent cytopenia(s). Overall, 15(55%) pts completed four cycles, while 3 pts didn’t complete four cycles of 177Lu DOTATATE due to hematotoxicity. Conclusions: Pts with advanced NETs and extensive/innumerable bone metastases treated with PRRT could be at higher risk for myelosuppression than historical controls. Our study highlights the importance of carefully monitoring and assessing hematological parameters in pts being considered for 177Lu DOTATATE with extensive/innumerable bone metastasis. [Table: see text]

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell non-Hodgkin lymphoma that originates in lymphoid tissue of epithelial lined structures. The commonest site for this lymphoma is the stomach (gastric MALT lymphoma). MALT lymphoma in other mucosal sites, including other gastrointestinal sites, lungs, salivary glands, and lacrimal glands, has been well-described. However, MALT lymphoma in urothelial organs (kidneys, ureters, and urinary bladder) has not been well-characterized. This study aimed to investigate the clinicopathological features and therapeutic outcomes in urologic MALT lymphoma (U-MALT). Methods: We identified patients with U-MALT who were treated at the Mayo Clinic Cancer Center between March 2013 and May 2022 through electronic medical chart review. Clinical, pathologic, radiologic, therapeutic, and survival data were extracted. Kaplan-Meier analysis was used to determine the survival outcomes. Results: The characteristic features of six patients (N=6) with U-MALT are summarized in Table-1. 4/6 (67%) are Caucasian, and 3/6 (50%) are males. The median age at diagnosis was 73.5 years. Urologic sites are the urinary bladder (3/6), kidneys (3/6), and ureter (1/6, this patient had both kidney and ureter involvement). 4/6 patients had primary U-MALT. Concurrent non-urologic involvement was identified in 3/6 patients and included bone marrow, lungs, stomach, and axillary lymph nodes. Bone marrow involvement was observed in 2/6 patients.Next-generation sequencing was performed on one patient's peripheral blood, revealing an ATM mutation. Regarding the initial clinical presentation, kidney-involved U-MALT patients presented with renal failure, and those with urinary bladder/ureteric involvement, U-MALT was diagnosed incidentally upon cystoscopic evaluation and biopsy. Various management strategies were used, including observation, surgical resection, and rituximab treatment. Notably, all patients achieved complete remission (CR) except one with partial response to rituximab, who subsequently achieved CR with the Bendamustine/Rituximab regimen. Median follow-up is 6 years (range, 1-10). All six patients are alive without relapse at the time of analysis, with the flat overall survival curve at 100%, indicating excellent long-term survival. Conclusions: Our study indicates that urologic MALT lymphomas are extremely rare and predominantly affect elderly people. The most common urologic sites are the kidneys and urinary bladder. Urologic manifestations are dependent on the urologic site involved. They can be primary to the urologic structures or part of the disseminated systemic marginal zone lymphoma. They can be treated like other low-grade lymphomas with observation, surgical resection, and systemic therapy. They appear to be quite responsive to CD-20 targeted therapy with Rituximab. Prognosis appears to be excellent with long overall survival. Further research with multi-institutional studies is needed to study this rare lymphoma entity and identify optimal therapy.

Introduction: Gray zone lymphoma (GZL) is a rare lymphoid neoplasm exhibiting features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma. Due to its rarity and relatively recent recognition by the World Health Organization in 2008, the natural history, clinical behavior, and best treatment strategies are still evolving. We present a retrospective review of GZL patients diagnosed and managed at the Mayo Clinic. This study aims to explore the clinical characteristics, treatment modalities, and outcomes of this poorly understood disease. Methods: After reviewing the electronic medical records of patients presented to the Mayo Clinic Cancer Center between March 2012 and July 2022 at the Mayo Clinic, we identified the patients who were diagnosed with GZL. Clinicopathological characteristics, disease features, treatment modalities, and outcomes were analyzed. The Kaplan-Meier method was utilized to assess survival outcomes. Results: Six patients (n=6) with GZL, all Caucasian and predominantly male 4/6 (67%), were identified. The median age at diagnosis was 37 years (range 24-57). Disease characteristics included high rates of mediastinal involvement 5/6 (83%) and bulky disease 4/6 (67%), with various stages of Ann Arbor classification represented. First-line treatment regimen varied between R-CHOP, ABVD, and DA R-EPOCH. The R-CHOP regimen was received in 3/6 patients (50%); the first patient achieved Complete Remission (CR), then managed with R-ICE, followed by consolidative autologous stem cell transplantation (auto-SCT) when relapsed. The second patient had Partial Response (PR) to R-CHOP and required consolidative radiotherapy to achieve CR, and the third R-CHOP patient achieved CR however, after multiple disease progressions that were managed with multiple regimens including R-ICE, R-CODOX-M/IVAC regimen, Nivolomab/Ipilumuab, consolidative radiotherapy, and Brentuximab vedotin. The ABVD regimen was received by 2/6 patients (33%). The first patient had CR, and the second patient had disease progression, which required treatment with R-ICE, followed by consolidative radiotherapy and auto-SCT. One patient (17%) received the DA R-EPOCH regimen and achieved CR, consolidated with auto-SCT. The median follow-up for our cohort is nine years (range, 5-13). All six GZL patients are alive and in CR (since 2019 or before) at the time of the study analysis, with an excellent flat overall survival curve. For this reason and due to the small patient sample, we could not calculate the progression-free survival data. Conclusions: Our Mayo Clinic review provides unique insights into managing Gray Zone Lymphoma (GZL), a rare disease. We reported 100% survival and remission in six GZL patients using diverse treatment strategies, contrasting with varied outcomes from other institutions. This underscores the potential of individualized treatments for GZL and the need for further, broader studies to validate our findings and refine optimal treatment approaches for this rare disease entity.

269 Background: There are strong data showing that patients (pts) with metastatic non-small cell lung cancer (NSCLC) receiving chemotherapy experience better quality of life (QOL) and longer overall survival (OS) when palliative care (PC) services are integrated early in their treatment course. Therefore, at our cancer center, pts with stage IV NSCLC have been referred to PC by oncology providers. In this study, we evaluated the uptake of PC services, specifically in pts with NSCLC who received immune checkpoint inhibitors (ICIs). ICIs have been considered to have less severe or less frequent adverse effects as compared to chemotherapy, possibly leading to fewer referrals to PC. Methods: We conducted a retrospective review of all pts at the Mayo Clinic Cancer Center in Florida who received single-agent ICI therapy for the treatment of stage IV NSCLC at any point between July 1, 2015, and July 1, 2022. The primary aim was to evaluate the uptake of PC services before or during treatment with ICIs. Descriptive statistics were used to characterize pt demographics and outcomes. Results: 129 pts were identified. 53.4% were male, and 46.6% were female. The majority of pts (84.4%) were white. 62 pts (48.0%) were seen by a PC provider before or during ICI treatment; 41 of these (31.7%) were seen by PC after starting ICI therapy. When grouped by year of ICI initiation, 30/73 pts (41.0%) treated between 2015 and June 2018 were seen by a PC provider, as compared to 15/31 pts (48.3%) treated between July 2018 and June 2020 and 17/25 pts (68.0%) treated between July 2020 and July 2022. Interestingly, the majority of pts who received PC services in the 2020-2022 group (12/17, or 70.5%) were seen by a PC provider for the first time prior to ICI initiation, whereas the majority of pts who received PC services prior to July 2020 (37/45, or 82.2%) were seen by a PC provider for the first time after ICI initiation. The mean number of PC visits increased from 1.59 in the 2015-2018 group to 1.84 in the 2018-2020 group and 4.96 in the 2020-2022 group. Conclusions: Uptake of PC services in pts with stage IV NSCLC receiving single-agent ICIs at our cancer center has increased over time, which is encouraging. Nevertheless, the numbers remain suboptimal, with less than 70% of pts receiving PC services. We plan to develop a multidisciplinary quality improvement project involving implementation of a mechanism to ensure that most patients with stage IV NSCLC, regardless of the type of systemic treatment they receive, are receiving PC services.

Abstract Background The efficacy of pembrolizumab monotherapy in metastatic castration-resistant prostate cancer patients when stratified by MSI-H and/or TMB-H is poorly defined. Additionally, outcomes based on sequencing source (i.e., tissue or liquid biopsy) have not been well described. We sought to assess outcomes of pembrolizumab monotherapy in patients with mCRPC and compare efficacy based on MSI-H and/or TMB-H when identified by tissue or liquid biopsy. Methods A retrospective analysis was performed of mCRPC patients treated at Mayo Clinic with pembrolizumab monotherapy between 2018 and 2023. Objective response rates (ORR), median progression-free survival (mPFS), and overall survival (mOS), were determined by RECIST v1.1 criteria. Results Twenty-two patients with mCRPC received pembrolizumab monotherapy for at least 3 cycles for an MSI-H or TMB-H indication. All patients had next generation sequencing (NGS) performed via tissue (n = 11) or liquid (n = 10) biopsy source. The ORR was 50% (27.3% complete response and 22.7% had partial response). The mPFS for TMB 10-14.9 mut/Mb (n = 4), TMB 15-24.9 mut/Mb (n = 6), and TMB ≥ 25 mut/Mb (n = 10) was 2.1, not reached (NR), and NR, respectively (p = 0.0003). The mOS for these same groups was 5.1 months, 20.5 months, and not reached, respectively. Among patients with TMB-H without co-occurring MSI-H or CDK12 (n = 6), none experienced a response and only one patient had stable disease compared to patients with MSI-H (n = 12) for whom the ORR was 75%. Immunotherapy responsive alterations such as ATRX and PTCH1 mutations were frequently noticed among patients who had complete response (CR). Conclusions Our study highlights that MSI-H drives the efficacy of pembrolizumab in mCRPC with better survival outcomes as TMB increases. Clinicians should consider alternative treatment strategies for advanced prostate cancer when TMB-H is present without co-occurring MSI-H or CDK12. This study further demonstrates the utility of liquid biopsy NGS for identifying MSI-H and/or TMB-H disease.

e24104 Background: There is a high rate of anemia present in cancer patients and anemia is also a common referral to a hematologist. Symptomatic anemia can significantly impair an individual’s functional status so identifying its cause is essential for improving quality of life. Correction of nutritional deficiencies, like iron, B12, and folate deficiency can improve hemoglobin counts, prevent recurrent PRBC transfusions, and can often resolve the anemia. In a busy academic hematology oncology practice, we hypothesize that it is easy to overlook performing a basic nutritional evaluation especially in the setting of other causes for anemia such as chemotherapy, hemolysis, blood loss, chronic kidney disease, and other disorders. We aim to evaluate the frequency of anemia workup in the hematology and oncology division at our academic institution. Methods: We conducted a retrospective study of all hematology oncology patients seen in our clinic who received a blood transfusion in 2021. All patients were 18 years old or order and received at least one-unit PRBC transfusion as an outpatient. One “transfusion event” was defined as any number of PRBC transfusions on a single day and any subsequent transfusions within a 90-day periods. A single patient, therefore, can have multiple distinct transfusion events. We analyzed whether patients received a “basic” anemia evaluation, defined as checking ferritin, iron saturation, B12, and folate levels within 3 months before or after the first transfusion, and whether a discrepancy in practice patterns exists between different hematology oncology subspecialties. Results: At the interim analysis, we identified 368 transfusion events for 275 patients. Those events were ordered by providers (physician, nurse practitioner, or physician assistant) in the following subspecialties: oncology (n = 20), malignant hematology (n = 18), classical hematology (n = 3), and fellow-in-training (n = 5). A basic anemia workup was missing in 58% (84 of 146), 27% (49 of 183), 23% (8 of 35), 40% (2 of 5) in the above groups respectively. For patients with macrocytic anemia defined as mean corpuscular volume (MCV) > 100 fL, 48% (38 of 79) did not have B12 or folate levels checked within 3 months before or after a transfusion event. For patients with MCV < 80 fL, 47% (14 of 30) did not have ferritin or iron saturation checked within 3 months before or after a transfusion event. Conclusions: We observed a high percentage of cancer and non-malignant hematology patients who did not receive a basic anemia evaluation within three months before or three months after a blood transfusion. A higher percentage of patients with solid tumors patients who required PRBC transfusions did not receive a basic anemia evaluation in a timely manner. Our study identified an area of quality improvement and need for intervention that can easily be overlooked in a busy academic hematology oncology practice.

e21156 Background: Immunotherapy (IO) is one of the major treatments for patients with metastatic non-small cell lung cancer (mNSCLC). IO may be discontinued in patients for many reasons, the most common being progression of disease (POD). For those patients who discontinued IO for reasons other than POD, such as immune-related adverse event (irAE), there is limited data that compare progression-free survival (PFS) and overall survival (OS) when IO is continued vs. stopped. Methods: We conducted a retrospective study of all patients with mNSCLC (stage IV) treated with IO at our institution from 2011 to 2022. Patients who discontinued IO due to POD were excluded from the analysis. The clinical outcomes, including PFS, OS, and irAE were investigated among patients with no POD who stopped IO prior to 6 or 12 months (m) vs. those that continued IO > 6 or 12m. Results: The analysis at the 6m timepoint included 92 patients, 82.6% were white, 50% were male, 67.4% had adenocarcinoma, and 82.6% used tobacco. The most common site of metastasis was bone (28.3%), followed by CNS (20.7%). 51.2% of patients had received IO as the first line systemic therapy and 32.6% received it as their second. Pembrolizumab was the most used IO (84.78%). Among these patients, 25 discontinued IO before 6m, and 67 patients continued IO beyond 6m. irAE, of any grade, occurred in 44.0% vs 37.3% when comparing IO discontinued with IO continued group at 6m. Patients who continued treatment beyond 6m had a longer duration of PFS (22.8m vs 11.8m, p = 1.14E-04) with a significant increase in OS (34.5m vs 14.0m, p = 1.34E-07). The analysis at the 12m timepoint included 71 patients, 87.3% were white, 46.5% were male, 78.9% had adenocarcinoma, and 80.3% used tobacco. The most common site of metastasis was bone (29.9%), followed by CNS (22.5%). 62.0% of patients had received IO as the first line systemic therapy and 28.7% received it as their second. Pembrolizumab was the most used IO (87.3%). Among these patients, 30 discontinued IO before 12m, and 41 patients continued IO beyond 12m. irAE, of any grade, occurred in 36.7% vs 41.5% when comparing IO discontinued with IO continued group at 12m. Similarly, patients who continued treatment beyond 12m had a longer duration of PFS (28.4m vs 14.2m, p = 1.91E-06) with a significant increase in OS (39.9m vs 17.6m, p = 3.45E-09). Conclusions: We observed that patients with mNSCLC and no POD, who continued IO beyond 6m and 12m, experienced a significant increase in PFS and OS than those who discontinued IO, with more significant increases in those who continued IO past 12m. These findings need to be verified in a larger cohort.

e16621 Background: Adrenocortical carcinoma (ACC) is an exceedingly rare aggressive endocrine malignancy with about 1 new case per million people diagnosed annually in the US. Higher incidence of ACC has been reported in patients (pts) with inherited syndromes such as Lynch syndrome and Li-Fraumeni syndrome. However, the incidence rate of developing multiple primary cancers in this population is unknown. The aim of this study is to investigate the frequency of additional malignancies in ACC patients. Methods: Using the Mayo Clinic Cancer Registry, we identified 63 pts who were treated for ACC from 2010- 2018 with updated follow up data until 01/31/2023. Electronic medical records were reviewed. Results: Among the patient cohort, 22 pts were male. 18/63 (29%) pts were found to have at least one additional malignancy, including basal cell carcinoma (3/18, 17%), melanoma (3/18, 17%), thyroid cancer (3/18, 17%), prostate cancer (3/18, 17%), squamous cell carcinoma of skin (2/18, 11%), renal cell carcinoma (2/18, 11%), breast cancer (2/18, 11%), leukemia (2/18, 11%), lung cancer (1/18, 6%), transitional cell malignant neoplasm of kidney (1/18, 6%), squamous cell carcinoma of tonsil (1/18, 6%), ovarian cancer (1/18, 6%), seminoma (1/18, 6%) and bladder cancer (1/18, 6%). 8/18 (45%) pts had more than one (2-3) non-ACC malignancies. The median age at diagnosis of ACC was 56 years (02-83). The median age at diagnosis of non-ACC malignancies was 54 years (25-72). Most of the patients (13/18) were diagnosed with non-ACC malignancy within 5 years of diagnosis of ACC. Most pts (13/18, 72%) were diagnosed with non-ACC malignancy first. Germline mutation information was not available except for 2 pts with known family history (FH) of Lynch syndrome and 2 pt with a known FH of Li-Fraumeni syndrome. FH was available in 38 pts, out of which 29 pts had FH of cancer identified in first-degree relatives. Among the 18 pts with additional malignancies, 12 pts had FH of cancer in first-degree relatives. All except 2 pts underwent curative treatment for their non-ACC malignancies, and 14 pts had no evidence of disease at death or the time of last follow-up. Conclusions: The rate of other multiple primary malignancies in pts with ACC is high, indicating possible genetic predisposition associated with this disease; Early genetic consultation and evaluation for known and novel germline mutations may need to be considered for these pts to improve long-term outcomes.