Hematology Oncology Associates

Hypertension and osteoporosis are prevalent chronic conditions that frequently coexist, particularly in aging populations. Increasing evidence indicates that they share interconnected pathophysiological pathways involving calcium metabolism, chronic inflammation, oxidative stress, and hormonal regulation. Diet is a critical adjustable factor that influences the onset and progression of both conditions. This review evaluates the impact of dietary modification, including adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, the Mediterranean diet, sodium restriction, and targeted nutrient intake (e.g., calcium, vitamin D, potassium, and magnesium), on bone mineral density (BMD) in individuals with treated and untreated hypertension. While the DASH diet effectively reduces blood pressure, its potential to lower BMD in the absence of adequate calcium intake warrants caution. In contrast, the Mediterranean diet provides broader nutritional support for both vascular and skeletal health through its anti-inflammatory and antioxidant profile. Diets rich in dairy products, minerals, and bioactive compounds are associated with improved BMD and vascular function. This review combines current evidence, explains mechanistic links between diet, bone, and cardiovascular physiology, and offers evidence-based dietary recommendations to address the coexisting conditions of hypertension and osteoporosis.

51 Background: Timely biomarker testing is essential for guiding treatment in non–small cell lung cancer (NSCLC). Reflex biomarker testing, ordered by pathologists, integrates biomarkers into the diagnostic process. However, CMS policies, particularly the 14-Day Rule and lack of clarity on ordering authority, limit the use of reflex testing, disrupting standardized workflows and delaying care. This study explores how these policies affect cancer care delivery. Methods: In early 2025, LUNGevity Foundation, with the Association for Molecular Pathology and the American Society for Clinical Pathology, surveyed 115 healthcare professionals to determine the prevalence of standardized workflows, pathologist-ordered biomarker testing, and application of the 14-Day Rule. Results: Findings indicate strong support for pathologist-ordered biomarker testing for reflex testing and timely diagnosis. Most respondents (94%) agreed CMS should recognize pathologists as ordering physicians, with 49% preferring this recognition be provided through guidelines. The majority (74%) strongly agreed this change would improve patient care. Standardized protocols - especially with in-house testing - were more common when pathologists ordered biomarker testing. Yet at 42% of sites using or considering such protocols, pathologists were not the ordering physician. Among these, 57% wanted implementation guidance, and 46% sought regulatory or compliance clarity for how to implement pathologist-initiated testing. Application of the 14-Day Rule varied: 22% applied it to inpatients, 13% to both inpatients and outpatients, and 23% were unsure. Regardless, 78% of those applying the 14-Day Rule said it caused treatment delays, and 40% reported treatment was selected before results were received. When asked how costs of multi-gene panels for in-patients with advanced-stage cancer are managed, 30% of respondents said the laboratory absorbs the cost, and 39% were unsure. Conclusions: Hospitals face the challenge of navigating regulations that impact care delivery - particularly the 14-Day Rule and unclear policies on pathologists' role in ordering biomarker panels, which influence implementation of reflex biomarker testing in the NSCLC diagnostic process. Respondents strongly supported pathologist-ordered testing as essential for reflex workflows and improved patient care. The 14-Day Rule was cited as a barrier to timely treatment, and a cause of financial strain when hospitals bypass the policy to expedite testing. Many were uncertain how testing costs are managed under current constraints, highlighting the need for clearer institutional policies. Hospital administrators should assess the impact of these regulations on care delivery and consider workflow adjustments in collaboration with pathology and oncology. Further research will gather broader input to guide recommendations to CMS, pathologists, and oncologists.

2584 Background: CD47-targeting agents face challenges, including “on-target, off-tumor” toxicities affecting red blood cells, limited efficacy, and manufacturing complexities. Clinical holds and discontinued trials highlight these difficulties. These issues have constrained their therapeutic potential and broadened the need for better solutions. HCB101 is an engineered human SIRPα fused to human IgG4 crystallizable fragment (Fc) protein developed using the proprietary FBDB platform, blocks the signal of the SIRPα-CD47 pathway, enhancing macrophage-mediated phagocytosis. Preclinical studies show HCB101’s potent antitumor activity across solid tumors and hematological malignancies. HCB101’s safety profile in repeat-dose cynomolgus monkey toxicity studies revealed acceptable red blood cell or platelet abnormalities, supporting its potential as a best-of-the-kind SIRPα-CD47 directed immunotherapy. Methods: This Phase 1, open-label, dose-escalation trial evaluates HCB101’s safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in advanced solid tumors or non-Hodgkin lymphoma (NHL) in the US, Taiwan, and mainland China. Eligible adults have treatment-refractory cancers, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. The 3+3 dose-escalation Bayesian Optimal Interval (BOIN) design assesses dose-limiting toxicities (DLTs) in the first 28-day cycle. Secondary endpoints include objective response rate (ORR), duration of response, and progression-free survival. Exploratory endpoints include CD47 receptor occupancy (RO), correlating response, and immune cell infiltration (NCT05892718). Results: 32 participants (median age 61 years; 74% male) enrolled across 7 escalating cohorts (0.08-5.12 mg/kg, QW). Patients had a median of 4 prior regimens. 68% had solid tumors, and 32% had NHLs. HCB101 was well tolerated, only 1 DLT reported at 2.56 mg/kg dose level (G3 platelet decrease). The most common treatment related AEs were anemia (17%), all grade 1or 2, that did not require blood transfusion or other treatments. HCB101 systemic exposure increased in a dose-dependent manner. Preliminary efficacy showed 29% stable disease (6 patients) in 21 evaluable patients, with 2 patients have SD > 16 wks, and 1 patient has SD > 23 wks. Doses ≥1.28 mg/kg achieved ≥90% CD47 RO in peripheral T cells. Conclusions: HCB101 demonstrated an acceptable safety profile and preliminary antitumor activity in heavily pretreated advanced cancer patients. These findings support its further clinical development, including expansion cohorts to evaluate efficacy in specific tumor types or in combination with other agents. Clinical trial information: NCT05892718 .

2600 Background: I-CHECKIT is a prospective observational study whose primary objective is to develop and independently validate a risk prediction model for the development of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher non-hematological irAEs in patients with solid tumors during the first year of treatment with ICI. Methods: Any patient initiating ICI per their treating oncologist and National Comprehensive Cancer Network guidelines was eligible to participate in this study. Eligibility criteria were unrestrictive and included participants with active autoimmune disease, decreased performance status, and any stage of cancer. One important exclusion criterion was planned receipt of ICI with chemo, biological or targeted therapy. Hormonal therapy and palliative radiation were allowed. The study is close to accrual in May 2024. Here we describe baseline participant characteristics. Results: Of a total of 2084 enrolled participants, 62 were ineligible. Community based NCORP sites enrolled the majority (n= 1,181, 56%) of participants. Participants were also enrolled from SWOG Latin American sites and Veteran Affairs (VA). 31% (n=656) had skin cancer (melanoma 90%, squamous 5% and Merkel cell 2.9%), 29% (n=604) had lung cancer and 12% (n=256) had kidney cancer. 17% (n=346) received combination ICI. The median age was 69.9 years. 64% were male, 90% (n=1866) were white, 8% (n=165) Hispanic/Latino, 5% (110) black, and 1% (16) Asian. 12% had performance status (PS) 2 or greater. 67% of the participants were overweight or obese. 9% (n=180) of the participants had active autoimmune disease such as rheumatoid arthritis, Type I diabetes, hypothyroidism, psoriasis, Crohn’s, ulcerative colitis. 3% (n=54) had a history of autoimmune disease not currently requiring treatment. Conclusions: The I-CHECKIT observational study enrolled participants representative of a real-world population, as most of the participants were from community practices such as NCORP. Most participants had melanoma, resulting in a higher proportion of white participants. 9% of this population had baseline active autoimmune disease, a population excluded in initial clinical trials, highlighting the broader use of ICI in daily clinical practice. Clinical trial information: NCT04871542 . Baseline characteristics. Age All No (%) Single ICI No (%) Combo ICI No (%) Skin No (%) Lung No (%) 61-65 years 301 (14) 244 (14) 57 (16) 94 (14) 91 (15) 66+ years 1324 (64) 1119 (64) 205 (59) 372 (57) 430 (71) PS 0-1 1822 (88) 1523 (88) 299 (87) 607(93) 500(83) 2 and + 258 (12) 211 (12) 47 (14) 48 (7) 101 (17) Active Autoimmune 180 (9) 153 (9) 27 (8) 54 (8) 51 (8) Hypothyroidism 113 (9) 97 (9) 16 (8) 28 (8) 34 (8) Type I Diabetes 15 (1) 10 (1) 5 (1) 5 (1) 4 (1) Psoriasis 11 (1) 9 (1) 2 (1) 3 (0) 3 (0)

A 19-year-old male with history of depression, cannabis use, and tobacco use presented to the hospital a few days after ingesting an unspecified number of nails, cylindrical batteries, coins, and BB gun pellets. On presentation, he was hemodynamically stable and denied any abdominal symptoms. In addition, his physical examination was benign. The patient was managed with a bowel regimen consisting of scheduled docusate sodium, lactulose, polyethylene glycol powder, and senna. He also received polyethylene glycol solution on several days. The patient was able to pass all of the nails, batteries, and coins prior to discharge. Some BB gun pellets remained at the time of discharge, but they were considered low risk for perforation. Our case illustrates that a suitable bowel regimen, rather than surgical or procedural intervention, can be used in certain situations to manage foreign object ingestions.

BackgroundHBI–8000, an oral selective HDAC inhibitor has demonstrated extensive effects on immune cell function in the tumor microenvironment. HBI-8000-302 is a Phase 1b/2 trial evaluating the combination of HBI–8000 with nivolumab (an anti-PD1 immune checkpoint inhibitor) in advanced melanoma, kidney cancer and non-small cell lung cancer. The recommended Phase 2 dose of HBI-8000 was determined to be 30mg orally twice weekly (BIW) combined with intravenous nivolumab administered at the manufacturer’s approved dosing schedule.MethodsPatients with metastatic melanoma not previously treated with anti-PD(L)-1 inhibitor, with measurable disease, ECOG performance status 0–1, and adequate hematologic and biochemical parameters were enrolled. Previously treated stable brain metastases not requiring steroids were permitted. Disease status was assessed by standard imaging using RECIST v1.1 every 8 weeks. Treatment was continued until disease progression, unacceptable toxicity or completion of 24 months of therapy. Final analysis of data as of March 9, 2023 is presented here.ResultsThirty-nine (39) eligible patients were enrolled and received HBI-8000 (37 at 30 mg BIW in Phases 1b and 2, and 2 at 40mg BIW in Phase 1b) in combination with nivolumab. Median age was 63 years (range 28–83); 59% were male; 34/39 (87%) had normal LDH; 16/39 (41%) had M1c disease, none with CNS metastases. The most common treatment–related > grade 3 adverse events (AEs) included colitis (n=4), fatigue, decreased appetite, pancreatitis, and diarrhea (n=3 each), abdominal pain and weight loss (n=2, each). Most common treatment related laboratory grade ≥3 AEs included hypophosphatemia (n=9), neutropenia (n=8; no febrile neutropenia), lymphopenia (n=6), anemia (n=3), increased ALT and thrombocytopenia (n=2 each). Seventeen patients discontinued treatment due to AEs. Among 38 patients evaluable for efficacy, the overall response rate was 65.8% including 6 (15.8%) completes responses (CR) and 19 (50%) partial responses (PR). The clinical benefit rate (CR, PR or stable disease lasting at least 12 weeks) was 87%. The median follow-up was 37 months; median progression-free survival was 36.9 months (95% CI: 6.7, NE). Median duration of response was not reached at the time of this analysis.ConclusionsThe combination of HBI-8000 and nivolumab demonstrated excellent efficacy and good tolerability in the treatment of anti-PD(L)-1-naïve advanced melanoma. Based on these encouraging results, a global Phase 3 trial evaluating HBI-8000 combined with nivolumab versus nivolumab alone as first-line treatment of unresectable or metastatic melanoma is currently ongoing.Trial RegistrationNCT02718066.Ethics ApprovalThe study was approved by participating study sites’ Institutional Review Boards and the Sponsor has conducted the trial in full compliance with all GCP and FDA regulations.

BackgroundALG.APV-527 is a bispecific antibody targeting costimulatory receptor 4-1BB (CD137) and the oncofetal tumor-associated antigen 5T4. 5T4 is expressed by multiple solid tumor types, such as non-small cell lung cancer, breast cancer, pancreatic, and gastrointestinal cancers with minimal expression in normal tissue. 4-1BB is an activation-induced costimulatory receptor that regulates immune responses of activated tumor-specific CD8 T cells and natural killer cells. ALG.APV-527 is designed to deliver a 5T4-conditional 4-1BB–mediated antitumor activity and minimize systemic immune activation and toxicity. Preclinically, ALG.APV-527 demonstrates robust antitumor activity by inhibiting the growth of established tumors expressing human 5T4 followed by a long-lasting memory immune response,1 providing a rationale for evaluating ALG.APV-527 in patients with advanced solid tumors with the possibility of combining with immune checkpoint inhibitors (ICI).MethodsThe Phase 1 study is a first-in-human, open-label, multicenter trial consisting of up to six cohorts (0.1–15 mg/kg) in a 3+3 dose escalation of ALG.APV-527 monotherapy, administered intravenously Q2W, in adult patients with advanced solid tumors. Eligibility is limited to patients with tumor types identified as likely to express 5T4. Key endpoints include safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamic activity and clinical antitumor activity of ALG.APV-527.ResultsALG.APV-527 has been well tolerated in 18 enrolled patients, including 2 patients enrolled in dose level 5 (12 mg/kg). Enrollment and assessment of dose level 5 is ongoing. Most treatment-emergent adverse events (TEAEs) were mild to moderate and manageable in the clinic; Grade 1 (G1): 31 (41%), G2: 33 (43%), G3: 9 (12%), G4: 3 (4%), G5: 0. One patient experienced a G4 dose limiting toxicity of febrile neutropenia. MTD has not been determined. Pharmacokinetics was favorable: Serum concentrations were consistent with administered doses. Exposure is associated with changes in pharmacodynamic biomarkers reflecting ALG.APV-527 mode of action. Expression of 5T4 and 4-1BB was detected in tumor biopsies. Two heavily pretreated breast cancer patients experienced prolonged stable disease (SD) of over 7 months and 12 months (the second of which escalated to a higher dose level twice without any added adverse events and remains on study).ConclusionsAvailable data for ALG. APV-527 treatment demonstrates good tolerability, safety, biological activity, and prolonged SD in some patients suggesting clinical benefit of treatment. Upon determining the optimized dose, subsequent development will likely take place as a combination treatment.ReferenceNelson MH, Fritzell S, Miller R, Werchau D, Van Citters D, Nilsson A, Misher L, Ljung L, Bader R, Deronic A, Chunyk AG, Schultz L, Varas LA, Rose N, Håkansson M, Gross J, Furebring C, Pavlik P, Sundstedt A, Veitonmäki N, Ramos HJ, Säll A, Dahlman A, Bienvenue D, von Schantz L, McMahan CJ, Askmyr M, Hernandez-Hoyos G, Ellmark P. The bispecific tumor antigen-conditional 4-1BB x 5T4 agonist, ALG.APV-527, mediates strong T cell activation and potent anti-tumor activity in preclinical studies. Mol Cancer Ther. 2022;22(1).

e15529 Background: Since 1994, there has been a 51% increase in young onset colorectal cancer incidence rates, as reported by the National Cancer Institute. Recently, the U.S. Preventative Task Force revised its guidelines, recommending colorectal cancer screening to commence at age 45 rather than 50. This study aimed to explore sex differences in cancer incidence across various race and ethnicities, aiming to discern whether these differences are rooted in biological factors or environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology and End Result (SEER) program (2000-2020) was used to calculate male-to-female incidence rate ratios (MF IRR) for colon and rectal cancer, stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic), and age-standardized to the 2000 U.S. population for individuals under the age of 50 diagnosed with colon or rectal cancer. Results: A total of 82,238 patients with colorectal cancer under the age of 50 were identified in the study period. Of these, 43,255 (52.6%) were males and 38,983 (47.4%) were females. The incidence trends over the years were analyzed, revealing a steady increase, with the highest incidence found in 2019 (4,819, 5.8%) and the lowest in 2000 (3,189, 3.8%). Non-Hispanic Whites comprised 57.2% of the cases, while the second and third largest groups were Non-Hispanic Black (13.2%) and Hispanic (17.9%). Incidence rates were highest among the non-Hispanic American Indian/Alaskan Native population (8.6 per 100,000 cases), followed by the non-Hispanic Black population (8.4 per 100,000 cases), and lowest in the Hispanic population (5.7 per 100,000 cases). Young-onset colorectal cancer incidence rates exhibited a male predominance, with the MF IRR consistently > 1 every year across race and ethnicity. Non-Hispanic Asian/Pacific Islander had the highest MF IRRs (7 per 100,000 cases in males vs. 5.8 per 100,000 cases in females), while Non-Hispanic American Indian/Alaskan Native had the lowest MF IRRs throughout the years, with the lowest being in 2019 (5.1 per 100,000 cases in males vs. 12.6 per 100,000 cases in females). Conclusions: The MF IRR for young onset colorectal cancer showed no significant variation by race, implying a potential influence of biological factors. Notably, disparities in incidence rates were observed among different racial and ethnic groups, with the highest rates among non-Hispanic Black and non-Hispanic American Indian/Alaskan Native populations. Further research is warranted to pinpoint specific factors driving young onset colorectal cancer, facilitating targeted interventions for at-risk populations.