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December 2025 Oncology Conferences: Year-End Data from ASH, SABCS, and ESMO-IO

December 2025 Oncology Conferences: Year-End Data from ASH, SABCS, and ESMO-IO

As 2025 draws to a close, three major oncology conferences delivered substantial clinical trial data that will inform treatment decisions throughout 2026. The American Society of Hematology Annual Meeting (December 6-9, Orlando), San Antonio Breast Cancer Symposium (December 9-12), and ESMO Immuno-Oncology Congress (December 10-12, London) collectively presented results from over 50 Phase 3 trials across hematologic malignancies and solid tumors.

This analysis examines the key clinical findings, regulatory implications, and competitive dynamics emerging from December's conference season.

Multiple Myeloma: Bispecific Antibody and CAR-T Data

MajesTEC-3 Trial Results

The Phase 3 MajesTEC-3 trial randomized 587 patients with relapsed/refractory multiple myeloma (1-3 prior lines) to teclistamab plus daratumumab subcutaneous versus investigator's choice daratumumab-based regimens (DPd or DVd). At median 34.5-month follow-up, the combination demonstrated a PFS hazard ratio of 0.17 (95% CI 0.12-0.23; P<0.0001).

The 36-month PFS rates were 83.4% versus 29.7%. Overall survival also favored the experimental arm with HR 0.46 (95% CI 0.32-0.65; P<0.0001), translating to 83.3% versus 65.0% three-year OS rates.

Response metrics:

  • Overall response rate: 95.4% vs 32.1%
  • Complete response or better: 81.8% vs 16.8%
  • MRD negativity at 10⁻⁵ (among ≥CR): 89.3% vs 63.0%
  • MRD negativity at 10⁻⁶ (among ≥CR): 87.5% vs 41.8%

Safety data showed cytokine release syndrome in 60.1% of patients in the teclistamab-daratumumab arm, though no Grade 3 or higher CRS events occurred. ICANS was reported in 1.1%. Infection rates were 96.5% versus 84.1%, with Grade 3+ infections in 54.1% versus 43.4%. Deaths occurred in 15.9% versus 33.1% of patients.

CAR-T Therapy Updates

CARTITUDE-1 extended follow-up at 61.3 months reported median PFS of 50.4 months and median OS of 60.7 months in triple-class exposed patients with at least three prior lines. Approximately one-third of patients remained progression-free at five years.

CARTITUDE-4 34-month data showed 80.5% 30-month PFS in standard-risk patients (as-treated population), with 87.3% OS at 2.5 years. All 26 patients achieving MRD-negative complete response at 12 months remained progression-free at 30 months. Early mortality was numerically higher in the ciltacabtagene autoleucel arm (14% vs 12% within 10 months), including 19 post-infusion deaths with 12 attributed to infections.

Anitocabtagene autoleucel (anito-cel, Arcellx/Gilead) iMMagine-1 Phase 2 data showed 96% ORR and 74% CR/sCR rate at median 15.9-month follow-up. The 18-month PFS was 67.4% with 88.0% OS. MRD negativity at 10⁻⁵ reached 95% in evaluable patients. CRS occurred in 86% (mostly Grade 1), with 8% ICANS (1 Grade 3). No delayed neurotoxicities were observed.

Table 1: Phase 3 Multiple Myeloma Bispecific/CAR-T Trials

Trial Agent Line N ORR CR/sCR MRD⁻ (10⁻⁵) mPFS HR PFS CRS Any CRS G3+ ICANS
MajesTEC-3 Tec + Dara 1-3L R/R 587 95.4% 81.8% 89.3% NR 0.17 60.1% 0% 1.1%
CARTITUDE-4 Cilta-cel 1-3L R/R 419 84.6% 73% 63% NR 0.29 76.1% 1% 4.5%
iMMagine-1 Anito-cel ≥3L 117 96% 74% 95% 18mo: 67% 86% <1% 8%
MagnetisMM-30 Elra + Iber 2-4L 22 95.5% 45.5% TBD 68.2% 0% 9%
MonumenTAL-2 Talq + Pom R/R 35 85.7% 45.7% 78% <5% <5%
LINKER-MM4 Linvo mono NDMM 45 86% 95% ~50% 0% <5%

Abbreviations: Tec=teclistamab; Dara=daratumumab; Elra=elranatamab; Iber=iberdomide; Talq=talquetamab; Pom=pomalidomide; Linvo=linvoseltamab; NR=not reached

CLL: Fixed-Duration Therapy and BTK Inhibitor Comparisons

CLL17 Trial

The Phase 3 CLL17 trial randomized 909 treatment-naïve CLL patients to continuous ibrutinib, fixed-duration venetoclax-obinutuzumab (12 cycles), or fixed-duration venetoclax-ibrutinib (15 cycles). At 34 months median follow-up, both fixed-duration arms demonstrated non-inferiority to continuous ibrutinib for PFS.

Three-year PFS rates: venetoclax-obinutuzumab 81.1%, venetoclax-ibrutinib 79.4%, ibrutinib 81.0%. Hazard ratios versus ibrutinib were 0.87 (98.3% CI 0.54-1.41) for venetoclax-obinutuzumab and 0.84 (98.0% CI 0.53-1.32) for venetoclax-ibrutinib.

MRD data showed undetectable MRD in peripheral blood reached 73.3% with venetoclax-obinutuzumab versus 47.2% with venetoclax-ibrutinib versus 0% with ibrutinib. Bone marrow uMRD rates were 62.0%, 40.0%, and 0% respectively.

Pirtobrutinib Trials

BRUIN CLL-313 compared pirtobrutinib versus bendamustine-rituximab in 282 treatment-naïve CLL patients. The 24-month PFS was 93.4% versus 70.7% (HR 0.199; 95% CI 0.107-0.367; P<0.0001). The 24-month OS rates were 97.8% versus 90.8% (HR 0.257; P=0.0261). Grade 3+ treatment-emergent adverse events occurred in 40.0% versus 67.4%.

BRUIN CLL-314 provided head-to-head Phase 3 comparison against ibrutinib, with pirtobrutinib meeting non-inferiority for ORR while demonstrating numerically superior PFS. Atrial fibrillation/flutter rates were 2.4% versus 13.5% (P<0.0001).

BTK Degrader Data

Bexobrutideg (NX-5948, Nurix) Phase 1a/1b data in 126 patients with R/R CLL showed 83% ORR with median 22.1-month PFS despite median 4 prior therapies. No new-onset atrial fibrillation was observed. Activity was maintained regardless of BTK, PLCG2, or TP53 mutation status.

Table 2: Phase 3 CLL Trials Comparison

Trial Regimen N ORR CR uMRD PB uMRD BM 3yr PFS HR G3+ AE AF Rate
CLL17 (VO) Ven + Obi 303 84.2% 51.5% 73.3% 62.0% 81.1% 0.87 59.0% 13.9%*
CLL17 (VI) Ven + Ibr 305 88.5% 46.2% 47.2% 40.0% 79.4% 0.84 42.9% 23.8%*
CLL17 (I) Ibrutinib 301 86.0% 8.3% 0% 0% 81.0% Ref 28.5% 34.6%*
BRUIN CLL-313 Pirtobrutinib 141 94.3% 2yr: 93.4% 0.20 40.0% 1.4%
BRUIN CLL-313 BR 141 80.9% 2yr: 70.7% Ref 67.4% 0.7%
BRUIN CLL-314 Pirtobrutinib 331 87.0% 2.4%
BRUIN CLL-314 Ibrutinib 331 78.5% 13.5%
Bexobrutideg NX-5948 126 83% 2.1% mPFS 22.1mo 23% neut 0%

*Cardiac disorders overall; VO=venetoclax-obinutuzumab; VI=venetoclax-ibrutinib; I=ibrutinib; BR=bendamustine-rituximab

AML: Low-Intensity and Menin Inhibitor Combinations

PARADIGM Trial

The PARADIGM trial compared azacitidine-venetoclax versus intensive chemotherapy (7+3 or CPX-351) in fit, transplant-eligible AML patients, excluding those with FLT3 mutations, core binding factor, and NPM1-mutated patients under 60.

Event-free survival was 14.6 months versus 6.2 months (HR 0.61; P=0.017). The 30-day and 60-day mortality rates were 0% with azacitidine-venetoclax versus 3.5% and 4.7% with intensive chemotherapy. No patients in the low-intensity arm required ICU admission versus 9.8% in the intensive arm.

Menin Inhibitor Triplets

Revumenib combined with decitabine-cedazuridine and venetoclax in newly diagnosed NPM1-mutated or KMT2A-rearranged AML achieved 86% ORR, 76% CR rate, and 100% MRD negativity in responders. Ziftomenib triplet combinations with venetoclax and azacitidine in newly diagnosed NPM1-mutated patients produced 86% composite CR with 73% CR at median age 75 years.

In the relapsed/refractory setting, response rates varied by molecular subtype. With ziftomenib triplet combinations, NPM1-mutated patients achieved 65% ORR and 48% composite CR, while KMT2A-rearranged patients achieved 41% ORR and 28% composite CR. Venetoclax-naïve patients showed substantially better responses: 83% ORR in NPM1m and 70% in KMT2Ar.

Table 3: AML Menin Inhibitor Efficacy

Agent Trial Population N CR+CRh MRD⁻ mOS DLT Key Toxicities
Revumenib mono AUGMENT-101 R/R NPM1m 64 23% 64% 5% QTc 21%, DS 25%
Revumenib triplet SAVE ND NPM1m/KMT2Ar 21 81% 100% NR 0% DS 13%, FN 13%
Revumenib + IC Phase 1 ND KMT2Ar/NPM1m 26 92% 86% NR 0% FN 46%
Ziftomenib mono KOMET-001 R/R NPM1m 92 22% 61% 18.4mo <5% DS 25%
Ziftomenib triplet KOMET-007 ND NPM1m 37 86% 68% NR 0% FN 33%, DS 12%
Ziftomenib triplet KOMET-007 R/R NPM1m 48 48% 0% Thromb 36%
Ziftomenib triplet KOMET-007 R/R KMT2Ar 32 28% 0%

DS=differentiation syndrome; FN=febrile neutropenia; IC=intensive chemotherapy; NR=not reached

Gene Therapy for Sickle Cell Disease

Casgevy Pediatric Data

Vertex presented first pediatric data for exagamglogene autotemcel (Casgevy) in children ages 5-11. In sickle cell disease, 100% of evaluable patients (4/4) achieved VOC-freedom for ≥12 consecutive months, with longest VOC-free duration reaching 24 months. In adults and adolescents with longer follow-up, 100% of 45 patients achieved VF12, with mean VOC-free duration of 35.3 months (up to 67.7 months).

In transfusion-dependent beta-thalassemia, 98.2% (55/56) achieved transfusion independence for ≥12 months, with mean duration of 41.4 months. Pediatric TDT patients showed 100% (6/6) transfusion independence among evaluable patients. One fatal veno-occlusive disease occurred in a pediatric TDT patient, attributed to busulfan conditioning. No malignancies have been reported.

Lyfgenia Update

Lovotibeglogene autotemcel (Lyfgenia) commercial data showed 115 patients treated across Lyfgenia and Zynteglo programs, with 88% achieving complete VOC resolution. The malignancy signal remains: 2 patients developed AML (both died) and 1 patient developed MDS, all from earlier manufacturing cohorts. Lifelong monitoring with CBC every six months for at least 15 years is required.

Pociredir Oral Therapy

Pociredir (Fulcrum Therapeutics), an oral EED inhibitor, showed mean HbF increase of 9.9% (from 7.1% to 16.9%) at Week 6 with the 20mg dose. 58% of patients achieved ≥20% HbF. Hemolysis markers improved: 37% decrease in indirect bilirubin, 37% reduction in LDH, 33% decrease in reticulocytes. 50% of patients reported zero VOCs during treatment, with no treatment-related serious adverse events.

Table 4: Gene Therapy for Hemoglobinopathies

Therapy Company Mechanism Approval VOC-Free TI Rate (TDT) HbF Malig Signal Price
Casgevy Vertex/CRISPR BCL11A CRISPR Dec 2023 100% 98.2% >40% None $2.2M
Lyfgenia Genetix Lentiviral Dec 2023 88% HbAT87Q 2 AML, 1 MDS $3.1M
Zynteglo Genetix Lentiviral Aug 2022 89% Low ~$2.8M
Pociredir Fulcrum Oral EED inh Phase 1b 50% (0 VOC) 16.9% None TBD

SABCS 2025: Breast Cancer Data

monarchE Overall Survival

The monarchE trial reported first statistically significant OS benefit with a CDK4/6 inhibitor in adjuvant breast cancer. At 76.2-month median follow-up, abemaciclib plus endocrine therapy demonstrated OS HR of 0.842 (95% CI 0.722-0.981; P=0.027) versus endocrine therapy alone in HR+/HER2- node-positive high-risk early breast cancer.

Seven-year OS rates were 86.8% versus 85.0% (1.8% absolute difference). Seven-year iDFS was 77.4% versus 70.9% (6.5% absolute difference; HR 0.734). Seven-year DRFS was 80.0% versus 74.9% (5.1% absolute difference).

Subgroup analyses showed tumors <2cm derived greatest benefit (HR 0.48; 95% CI 0.358-0.646). Premenopausal women showed 42.2% risk reduction (HR 0.578; 95% CI 0.441-0.758). Benefit was consistent regardless of Ki-67 status: Ki-67 ≥20% HR 0.66; Ki-67 <20% HR 0.70.

Giredestrant (lidERA Trial)

The Phase 3 lidERA trial randomized 4,170 patients with stage I-III HR+/HER2- early breast cancer to giredestrant versus physician's choice endocrine therapy. iDFS HR was 0.70 (95% CI 0.57-0.87; P=0.0014). Three-year iDFS was 92.4% versus 89.6%. DRFI HR was 0.69. Interim OS showed HR 0.79 (data 31% mature).

Treatment discontinuation was lower with giredestrant (5.3% vs 8.2%). Bradycardia occurred in 11.3% versus 3.2%, mostly Grade 1 and asymptomatic.

Imlunestrant (EMBER-3)

Extended EMBER-3 follow-up showed median OS of 34.5 months versus 23.1 months (HR 0.60; P=0.0043) in ESR1-mutated patients—an 11.4-month survival advantage. The imlunestrant-abemaciclib combination achieved median PFS of 10.9 months versus 5.5 months for imlunestrant monotherapy (HR 0.59; P<0.0001), delaying time to chemotherapy by more than one year regardless of ESR1 mutation status.

Camizestrant (SERENA-6)

SERENA-6 data validated ctDNA-guided therapy switching. Patients who switched to camizestrant upon detection of emergent ESR1 mutations while on first-line AI plus CDK4/6 inhibitor achieved median PFS of 16.0 months versus 9.2 months (HR 0.44; P<0.0001). Two-year PFS was 29.7% versus 5.4%.

Table 5: CDK4/6 Inhibitor Adjuvant Trials

Trial Agent N Risk Population iDFS HR (95% CI) Abs iDFS OS HR P-value Key Toxicities
monarchE Abemaciclib 5,637 N+, high-risk 0.734 (0.657-0.820) 6.5% (7yr) 0.842 P=0.027 Diarrhea 76%, neut 45%
NATALEE Ribociclib 5,101 Stage II-III 0.716 4.9% (4yr) 0.800 P=0.026 nom Neutropenia, QTc
PENELOPE-B Palbociclib 1,250 Post-neoadj residual 0.93 (0.74-1.17) NS NS Neutropenia
PALLAS Palbociclib 5,796 Stage II-III 0.96 (0.81-1.14) NS NS Neutropenia

Table 6: Oral SERD/PROTAC Competitive Landscape

Agent Company Mechanism Phase Key Trial Setting Efficacy HR ESR1m Data Status
Elacestrant Stemline Oral SERD Approved EMERALD 2L+ mBC PFS 0.70 mPFS 3.8 vs 1.9 mo FDA Jan 2023
Imlunestrant Eli Lilly Oral SERD Approved EMBER-3 2L+ mBC PFS 0.62 mPFS 5.5 vs 3.8 mo FDA Sept 2025
Camizestrant AstraZeneca Oral SERD Phase 3 SERENA-6 ctDNA-switch PFS 0.44 mPFS 16.0 vs 9.2 mo Filing H1 2026
Vepdegestrant Arvinas/Pfizer PROTAC Phase 3 VERITAC-2 2L+ mBC PFS 0.57 mPFS 5.0 vs 2.1 mo PDUFA June 2026
Giredestrant Roche Oral SERD Phase 3 lidERA Adjuvant iDFS 0.70 Filing 2026

HER2+ Breast Cancer

DESTINY-Breast05

The DESTINY-Breast05 trial compared trastuzumab deruxtecan versus T-DM1 in HER2+ patients with residual invasive disease after neoadjuvant therapy. The iDFS HR was 0.47 (95% CI 0.34-0.66; P<0.0001). Three-year iDFS was 92.4% versus 83.7% with T-DM1. Distant recurrence was 5.1% versus 9.9% (HR 0.49).

ILD occurred in 9.6% of T-DXd patients, with two Grade 5 events (0.2%).

DESTINY-Breast09

First-line metastatic data showed T-DXd plus pertuzumab achieved PFS HR of 0.56 (95% CI 0.44-0.71; P<0.0001) versus taxane-trastuzumab-pertuzumab. Median PFS was 40.7 months versus 26.9 months. ORR was 85.1% versus 78.6%; CR rates were 15.1% versus 8.5%. FDA approval for this indication occurred December 15, 2025.

HER2CLIMB-05

HER2CLIMB-05 tested tucatinib plus trastuzumab-pertuzumab as first-line maintenance. PFS HR was 0.641 (P<0.0001). Median PFS was 24.9 versus 16.3 months. In HR-negative disease, HR was 0.554 (P=0.0002); in HR-positive disease, HR was 0.725 (P=0.0389). CNS-PFS nearly doubled: 8.5 versus 4.3 months.

Table 7: HER2+ Breast Cancer Trials

Trial Agent Setting N mPFS HR (95% CI) ORR CNS Activity ILD Rate
DESTINY-Breast05 T-DXd Adj residual 1,635 3yr iDFS 92.4% 0.47 (0.34-0.66) Fewer CNS mets 9.6%
DESTINY-Breast09 T-DXd + P 1L mBC 1,157 40.7 mo 0.56 (0.44-0.71) 85.1% Yes Consistent
HER2CLIMB-05 Tuc + HP Maint 654 24.9 mo 0.641 CNS-PFS 8.5mo
KATHERINE T-DM1 Adj residual 1,486 3yr iDFS 88.3% 0.50 No Low

Triple-Negative Breast Cancer

TROPION-Breast02

TROPION-Breast02 compared datopotamab deruxtecan versus chemotherapy in first-line PD-L1-negative TNBC. Median PFS was 10.8 months versus 5.6 months (HR 0.57; 95% CI 0.47-0.69; P<0.0001). Median OS was 23.7 months versus 18.7 months (HR 0.79; 95% CI 0.64-0.98; P=0.0291). ORR was 62.5% versus 29.3%.

ASCENT-04

ASCENT-04 tested sacituzumab govitecan plus pembrolizumab versus chemotherapy-pembrolizumab in first-line PD-L1-positive TNBC. Median PFS was 11.2 months versus 7.8 months (HR 0.65; 95% CI 0.51-0.84; P<0.001). Median duration of response was 16.5 versus 9.2 months. Neutropenia occurred in 65% (43% Grade 3-4). Treatment discontinuation was 12% versus 31%.

TNBC Prevention Vaccine

The α-lactalbumin vaccine (Anixa Biosciences/Cleveland Clinic) Phase 1 data in TNBC survivors and BRCA mutation carriers showed 74% of participants achieved immune responses. No serious adverse events occurred; only mild injection-site reactions were reported. Phase 2 trials are planned.

ESMO-IO 2025: Immunotherapy Data

IMA203CD8 TCR T-Cell Therapy

Immatics presented Phase 1a data for IMA203CD8 (PRAME-targeting TCR T-cell therapy) in 78 patients across melanoma, ovarian carcinoma, and synovial sarcoma. Confirmed ORR was 36% with best response ORR of 46%. Disease control rate at Week 6 was 84%. Median duration of response was 9.2 months. Seven responses remained ongoing for ≥1 year.

CRS distribution: Grade 1 (35%), Grade 2 (50%), Grade 3 (9%), Grade 4 (1%). No treatment-related deaths occurred.

SHR-1701 in Gastric Cancer

SHR-1701 (PD-L1/TGF-β bifunctional antibody, Hengrui) showed benefit in high-risk gastric/GEJ cancer. In 551 patients with high-risk features, median OS was 14.4 months versus 10.1 months (HR 0.62; 95% CI 0.49-0.78). Patients with liver metastases showed median OS of 16.8 versus 10.3 months (HR 0.46).

Neoadjuvant Melanoma

NADINA 2-year update confirmed 18-month EFS of 80.8% with neoadjuvant ipilimumab-nivolumab versus 53.9% with adjuvant nivolumab alone (HR 0.32). SWOG S1801 showed 3-year EFS of 68% versus 56% (HR 0.67) with neoadjuvant pembrolizumab.

Table 8: TCR T-Cell Therapy Solid Tumor Data

Agent Target Company Phase Tumor Types N ORR mDOR CRS Any CRS G3+
IMA203CD8 PRAME Immatics 1a MEL, OC, SS 78 46% 9.2 mo 95% 10%
Afami-cel MAGE-A4 Adaptimmune Approved Synovial sarcoma 44 43.2% 6.0 mo 75% 2%
TAEST16001 NY-ESO-1 1 Soft tissue 12 41.7% 13.1 mo Low Low

MEL=melanoma; OC=ovarian carcinoma; SS=synovial sarcoma

Corporate and Deal Activity

GSK-IDEAYA Termination

GSK terminated its IDEAYA partnership, returning Werner Helicase (IDE275) and Pol Theta (IDE705) programs to IDEAYA effective March 9, 2026. The original 2020 deal included $100 million upfront plus $20 million equity. IDEAYA maintains cash runway into 2030.

Other M&A

Ipsen completed acquisition of ImCheck Therapeutics, expanding its immunotherapy pipeline. Natera acquired Foresight Diagnostics for $275M plus $175M milestones, expanding MRD ctDNA capabilities.

Other notable 2025 oncology deals: J&J acquired Halda for $3B (prostate/lung); Sanofi acquired Blueprint for $9.5B; GSK acquired IDRx for $1.15B (GIST); BMS entered $1.5B license with BioNTech for PD-1xVEGF bispecific.

Table 9: December 2025 Corporate Activity

Companies Deal Type Assets Terms Rationale
Ipsen → ImCheck Acquisition IO pipeline Undisclosed Expand IO
Natera → Foresight Acquisition MRD ctDNA $275M + $175M Precision oncology
J&J → Halda Acquisition Prostate/lung $3B Oncology growth
BMS ↔ BioNTech License PD-1xVEGF $1.5B + $7.6B miles Bispecific access
Sanofi → Blueprint Acquisition Ayvakit $9.5B Oncology/rare
GSK → IDRx Acquisition IDRX-42 $1.15B GIST precision
AZ → EsoBiotec Acquisition In vivo CAR-T $425M + miles Cell therapy

Table 10: Key 2026 PDUFA Dates

Drug Company Indication PDUFA Date Priority Review
Vepdegestrant Arvinas/Pfizer ESR1m HR+/HER2- mBC June 5, 2026 Fast Track
Camizestrant AstraZeneca ESR1m HR+/HER2- mBC H1 2026 est
177Lu-edotreotide ITM GEP-NETs Aug 28, 2026 Standard
Zidesamtinib Nuvalent ROS1+ NSCLC Sept 18, 2026 Standard
Anito-cel Arcellx/Gilead R/R MM 2026 est Expected
T-DXd + THP Daiichi/AZ Neoadj HER2+ BC May 18, 2026 Standard

2026 Outlook

The December 2025 conference data positions several therapeutic classes for regulatory decisions and market entry in 2026.

In multiple myeloma, the MajesTEC-3 results will likely lead to regulatory submissions for teclistamab-daratumumab in earlier lines. The differentiated safety profile of anito-cel may enable broader CAR-T utilization if approved.

In breast cancer, the oral SERD class will see increased competition as camizestrant and vepdegestrant approach regulatory decisions. The monarchE OS data supports continued CDK4/6 inhibitor use in high-risk adjuvant populations. T-DXd has established itself as a platform therapy across HER2+ and HER2-low disease.

In CLL, fixed-duration regimens may shift standard practice away from continuous BTK inhibition, particularly given the cardiovascular safety data favoring newer agents.

The AML menin inhibitor triplets represent a potential shift toward low-intensity curative approaches in molecularly defined subsets.

Gene therapy for hemoglobinopathies continues to demonstrate durable benefit, though the safety contrast between Casgevy and Lyfgenia will influence market dynamics.


The information in this article is provided for informational purposes only. The author is not a lawyer, financial advisor, or licensed medical professional. This content does not constitute investment, legal, or medical advice.