Broder, Michael S.

Introduction: Systemic amyloid light chain (AL) amyloidosis is a rare disease with severe sequelae, including cardiac and renal dysfunction and failure. Various biomarker-based staging systems have been established to inform prognosis and treatment. However, a single International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code collectively applies to all stages of the disease, and while several studies have reported disease costs using healthcare claims data, stage-specific costs are not well understood. The current study aimed to estimate the healthcare utilization and costs of prevalent patients with AL amyloidosis by Mayo 2012 stage (I, II, III, IV). Methods: A multi-center medical chart review of patients with AL amyloidosis was conducted across six hematology clinics in the United States. Enrolled patients were ≥18 years old with a diagnosis of AL amyloidosis, documentation of Mayo 2012 stage at diagnosis, ≥1 office visit during the 6 months prior to the site's IRB approval date, and ≥1 year of available medical records. We collected 1 year of healthcare utilization data for each patient, in addition to clinical characteristics at diagnosis, which was prior to the 1-year observation period for most patients. Observation periods ranged from 11/2020 to 6/2023. Demographics, AL amyloidosis clinical history (e.g., organ involvement, lines of therapy, treatment response), laboratory values, and AL amyloidosis-related healthcare utilization (e.g., office visits, laboratory tests, procedures, medications, emergency department visits, inpatient stays) were collected. Patients were stratified by Mayo 2012 stage at diagnosis. Patients' 1-year healthcare costs were calculated by combining abstracted utilization data with the Centers for Medicare and Medicaid Services 2023 Physician Fee Schedule for procedures, Medi-Span® Price Rx® Pro for pharmacy and drug administration costs, and published literature for costs unavailable in these sources. Costs were adjusted to 2023 USD using the Consumer Price Index inflation calculator from the US Bureau of Labor Statistics. Results: The study included 61 patients: 15 stage I, 16 stage II, 17 stage III, and 13 stage IV. Overall, patients had a mean age at diagnosis of 62.4 years (standard deviation ([SD] 10.1), 39.3% were female (n=24), and 67.2% (n=41) of patients were non-Hispanic White, 14.8 % (n=9) Non-Hispanic Black, 6.6% (n=4) Asian, 1.6% (n=1) Hispanic, and 9.8% (n=6) other race/ethnicity. Most patients had Medicare (45.9%, n=28) or private health insurance (34.4%, n=21). The average duration of disease (i.e., time from diagnosis to date of last office visit prior to their site's IRB approval date) was 4.5 years (SD 3.5). All patients had involvement of ≥1 organ system and 45.9% (n=28) had involvement of ≥2 organ systems at diagnosis. More than half of patients had renal (55.7%, n=34) or cardiac (52.5%, n=32) involvement. Nearly all patients completed first-line therapy at any point prior to their last office visit (93.4%, n=57); a minority of patients (9.8%, n=6) initiated first-line therapy, and 3 patients (4.9%) had a hematopoietic stem cell transplantation, one each in stages I, II, and III, during the study period. The median estimated AL amyloidosis-related healthcare costs (USD) during the 1-year study period were $95,253 (interquartile range [IQR] $2,869-497,504) for stage I, $190,796 ($5,249-499,470) for stage II, $414,677 ($28,365-533,081) for stage III, and $523,504 ($191,830-526,596) for stage IV. Discussion: This is the first study of AL amyloidosis that reports costs of care stratified by Mayo 2012 stage. In a prevalent population with AL amyloidosis, we found that overall, patients with AL amyloidosis have significant ongoing costs of care after completion of initial therapy at each Mayo 2012 stage, with stage IV patients having the highest AL amyloidosis-related costs. The percent of patients with cardiac or renal organ involvement is possibly higher than represented in this study; given the rapid progression and high early mortality rate seen with stage III and IV disease, some of these patients may not have fulfilled the 1-year observation period requirement and thus were excluded from the study. These data describe the significant and continued burden faced by patients with AL amyloidosis and the health care system for the years beyond initial diagnosis and completion of front-line treatment.

Objective(s): PIK3CA-related overgrowth spectrum (PROS) is a group of disorders caused by somatic variants in the PIK3CA gene. We aimed to update recommendations on the severity classification, testing, and medical management of patients with PROS. Methods: Using validated consensus methodology, we convened a 13-member panel in 2020 and reviewed current evidence on how to diagnose and treat PROS. The panel was asked to rate the level of disease severity, and the appropriateness of whether to test for a mutation and medical therapy in 217 patient scenarios before a virtual meeting. Panelists discussed areas of disagreement and completed ratings following the meeting. Results: The panel developed clinical presentations and endorsed the disease severity framework defined by functional impairment, a reduction in quality of life, and risk of death. Panelists agreed it is appropriate to test for a PIK3CA gene variant in every moderately/severely affected patient. Panelists agreed it may be appropriate to consider an mammalian (mechanistic) target of rapamycin inhibitor in some severely affected patients and some moderately affected patients with progressive disease. Although clinical trials have only recently begun and the evidence remains limited, panelists also agreed it may be appropriate to consider treatment with phosphoinositide 3-kinase/serine/threonine protein kinase inhibitors in severely affected patients with a confirmed PIK3CA variant or without a confirmed variant but with progressive disease. Conclusion: These recommendations represent the consensus of experts informed by published literature and experience. Future research should validate this guidance using clinical data. Once validated, we hope these recommendations will improve outcomes for patients with PROS.

e18584 Background: Cancer progression rates following diagnosis are readily measured. However, the progression rate of cancer during the preclinical sojourn time is generally unobserved. Understanding the duration of preclinical stages (“dwell time”) would allow clinicians to better identify appropriate screening intervals for cancer. We therefore elicited estimates of progression rate during the preclinical sojourn time for a wide variety of malignancies from a panel of clinical experts. Methods: We used a validated consensus methodology (RAND/UCLA modified Delphi panel method) to elicit per-stage dwell time estimates for 20 solid cancers and lymphoma from experts. Eleven experienced oncologists (general and subspecialists) from community and academic centers reviewed literature on the natural history of disease and estimated in number of years (<1 to 9+ years) how long it would take each cancer to progress from the beginning of clinically detectable Stage I/II/III to the beginning of the next stage in untreated adults. Cancer histological subtypes were grouped and experts were asked to provide an overall rating. Ratings were completed before and after a discussion of areas of disagreement. Results: Expert estimates and range of dwell time for 21 cancer types are provided in Table. Prostate and thyroid cancer were estimated to be the slowest growing, taking approximately 7 and 5 years respectively to progress through Stage I (range 4-8), 5 years to progress through Stage II (range 3-7), and 3 and 4 (range 2-5) years respectively to progress through Stage III. Esophageal, lung, liver/intrahepatic bile-duct, gallbladder, and pancreatic cancers were estimated to progress quickly through all three stages (1-2 years per stage). Conclusions: These findings summarize practicing oncologists’ estimates of dwell time in preclinical disease. Experts agreed on dwell times although ranges were large and differences in cancer subtypes were not captured. Generally, estimates trend with published data on survival with treatment: cancers with higher survival (e.g., prostate, thyroid) were estimated to grow slower, while cancers with lower survival (e.g., pancreatic, liver/intrahepatic bile-duct, gallbladder) were estimated to grow faster. These estimates could be useful when determining screening intervals for these or any subset of these cancers. [Table: see text]

Background: Patients with cholangiocarcinoma often have indwelling biliary stents or catheters which are prone to obstructions and/or infections; studies show that 20–40% present with fever and/or jaundice requiring urgent treatment in the outpatient setting for which there are no uniform guidelines. The goal was to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: Thirteen expert physicians from relevant specialties, geography, and practice settings were recruited for the panel. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a scale from 1–9 and classified as appropriate, inappropriate, or uncertain. Scenarios with greater than 2 (>2) ratings of 1–3 (inappropriate) and greater than 2 (>2) ratings of 7–9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions and the UK (8%) and had practiced for a mean 16.5 years (4–33 years). Panelists rated 480 scenarios before the meeting and re-rated 288 of the clinical scenarios after the meeting. The panelists agreed that ongoing treatment with chemotherapy did not influence decision-making and, therefore, 192 scenarios were excluded from the final list. Disagreement decreased from 37.5% before to 10.4% after the meeting. Consensus on stent/tube manipulation and inpatient antibiotic therapy was obtained and summarized in patients as “appropriate” or “maybe appropriate” based on a patient’s bilirubin level at presentation. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in the urgent management of ascending cholangitis in patients with cholangiocarcinoma.

Background Migraine is associated with debilitating symptoms that can affect daily functioning. “My Migraine Voice” was a large, cross‐sectional, multi‐country online survey aimed at understanding disease burden directly from people with migraine. Objective This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. Methods The online survey was administered to adults with a self‐reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out‐of‐pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. Results Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out‐of‐pocket costs of $90.00 ($30.00, $144.00) in doctor’s fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out‐of‐pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. Conclusions Migraine impacts individuals’ activities of daily living, work‐life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out‐of‐pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

e15641 Background: CC pts with biliary stents or catheters are prone to have obstruction/infection and studies show 20-40% present with fever/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with > 2 ratings of 1-3 (inappropriate) and > 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years). Panelists rated 480 scenarios before the meeting, but re-rated only 288 clinical scenarios as they felt that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in the table below. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. (Support: The Cholangiocarcinoma Foundation). [Table: see text]

452 Background: CC pts with biliary stents or catheters often present with fever and/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed based on a literature review, and therapies were rated by the experts before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with > 2 ratings of 1-3 (inappropriate) and > 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years) and reported seeing an average of 120 unique CC patients a year (0-900 pts). Panelists rated 288 clinical scenarios. Experts decided that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in table 1. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. Studies of the impact of these guidelines on cost of care and pt outcomes are warranted. (Support: The Cholangiocarcinoma Foundation)[Table: see text]