Jean Bustamante-Alvarez MD MS

Erdafitinib in Patients with FGFR-Altered Advanced or Metastatic Cholangiocarcinoma @AACR doi.org/10.1158/1078-0… 👉ORR 55%, mDOR 6.9mo 👉mPFS 8.5mo, mOS 18.1mo 🧐consistent data across all FGFRi, some data for pts with FGFR3 gene alterations @myESMO @ASCOPost @EASLedu @ILCAnews

Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma @HEP_Journal doi.org/10.1097/HEP.00… 👏Timely guideline 👉still very difficult to treat tumor @ASCO @myESMO @EASLnews @ILCAnews

Are B7H3 ADCs next for lung cancer? Ph Ia/b trial of GSK5764227 @Cancer_Cell - 237pts - g3+ TRAEs ⬇️WCC, ANC, Hb - ORR 52.3% ES-SCLC; 22.4% NSCLC Pleased to be participating in Ph3 EMBOLD trial @CancerCentreIre 🇮🇪 @OncoAlert @cancertrials_ie #LCSM cell.com/cancer-cell/fu…

Just in: The phase 3 Talapro-3 trial met its primary endpoint!!! fiercepharma.com/pharma/pfizer-… @OncoAlert @AUC3_Official

Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer: The ORCHESTRA Randomized Clinical Trial @JAMAOnc doi.org/10.1001/jama.2… 🧐even with modern chemotherapies, tumor debulking does not add anything.... @myESMO @ASCO

Delighted to share results of phase 2 ILUSTRO in @NatureMedicine @KlempnerSam @ASCOPost Zolbetuximab+FOLFOX+nivo showed encouraging activity in CLDN18.2+ gastric cancer with mPFS 14.8 months (18months in high CLDN). Supporting the ongoing phase 3 LUCERNA. doi.org/10.1038/s41591…

Phase I ARTEMIS-001 trial of the B7-H3 ADC HS-20093 (GSK5764227) now @Cancer_Cell. In SCLC, RR 52%, DOR 7.1m with greater RR if topoisomerase I inhibitor naive vs treated (60% vs 17%), but no difference by platinum sensitivity. B7-H3 IHC not predictive. cell.com/cancer-cell/fu…

🧬 MSI-H/dMMR cholangiocarcinoma 📍 Real-world propensity-matched study (JHEP Reports) 👥 331 pts | MSI-H/dMMR: 6.9% 📊 ICIs-based therapy • mPFS 64.1 vs 7.2 mo • mOS 70.5 vs 14.0 mo (vs MSS) 🎯 MSI-H/dMMR emerges as a key predictive biomarker 🔗 doi.org/10.1016/j.jhep… @GrupoTTD @OncoAlert

Next-generation KRAS G12C inhibitor olomorasib shows promising pan-tumor activity in a first-in-human study. ORR ~37% in non-CRC tumors with durable response. Activity even observed after prior KRAS G12C inhibitors. KRAS targeting keeps evolving. nature.com/articles/s4146…

In an international, randomized trial involving patients with acute venous thromboembolism, the risk of clinically relevant bleeding was significantly lower with apixaban than with rivaroxaban during the 3-month treatment period. Full COBRRA trial results: nejm.org/doi/full/10.10…

RECITE: In a phase 3 trial in patients with persistent chemotherapy-induced thrombocytopenia, 84% of those receiving romiplostim had no chemotherapy dose modifications, as compared with 36% of those receiving placebo (odds ratio, 10.16). Full trial results: nejm.org/doi/full/10.10… Editorial: Thrombopoietin-Receptor Agonists in Chemotherapy-Induced Thrombocytopenia nejm.org/doi/full/10.10…

🎉Our latest research published in @CCR_AACR. doi.org/10.1158/1078-0… We provide the most comprehensive multiomic🧬 characterization to date of the B-cell 🫧 mediated immune response in resectable NSCLC 🫁 treated with perioperative chemoimmunotherapy (ChIO). @MARIANOPROVENCI

YouTube video link 2/x. youtube.com/watch?v=gJBZJd…

Have you ever wondered whether you need to hold systemic during RT due to concern for additive toxicity? See this 10 min video. Categorized by systemic type (cytoxic chemo, IO, TKI, BRAF, etc) & RT regimen (SBRT/conventional/palliative) Slides🧵& full video below. 1/8

Clinical Significance of MTAPDeletions and Their Overlap With Concurrent Oncogenic Driver Alterations Including EGFR in NSCLC jto.org/article/S1556-…

Real responses to the rezatapopt pill for p53 Y220C-mutant refractory cancers, published in @NEJM . Rare ~1% cancers. Is it time to note this p53 subtype in our pie chart for #NSCLC, as an actionable mutation?

Radiotherapy Review in NEJM: “Underuse and refusal of indicated radiotherapy have been shown to increase cancer-specific mortality and the risk of death in both curative and palliative settings” nejm.org/doi/full/10.10…

MPN (Myeloproliferative Neoplasms) Board/ITE Key Clinical Pearls 🩸🧬 Mnemonic🙂 “⚡JAK ate 🍁MAPL syrup when 📜CALR came to visit the 🏠MPN house'' MPN Categories 🔹 Chronic Myeloid Leukemia – BCR-ABL1 driven, highly treatable 🔹 Chronic Neutrophilic Leukemia – CSF3R mutation; transplant often needed 🔹 Chronic Eosinophilic Leukemia – clonal eosinophilia; transplant main option 🔹 JAK2-related MPNs: • Polycythemia Vera • Essential Thrombocythemia • Primary Myelofibrosis Driver Mutations 🧬 ⚡ JAK2 V617F – almost all PV, ~50% ET/PMF ⚡ CALR – common in JAK2-negative ET/PMF ⚡ MPL – less common ⚡ 10–20% triple-negative Diagnosis 🩺 • PV: ↑Hb + JAK2 → diagnosis likely • ET: mutation panel (JAK2/CALR/MPL) + CBC/smear • PMF:bone marrow + cytogenetics + NGS essential Not Every Erythrocytosis Is PV ⚠️ Common causes: 💊 SGLT2 inhibitors 💊 Testosterone ➡️ Check JAK2 first ➡️ Don’t stop beneficial meds automatically Major Risks in MPNs • Thrombosis • Symptoms / QoL 😴 • Leukemic transformation AML risk: • ET <5% • PV ~10% • PMF ~30% ET Management 🩸 🎯: prevent thrombosis PLT>450X109/L 🦶 Erythromelalgia, 🤕 Headache, 🩸 Clots 🔍 Diagnosis: BM Biopsy  with predominent predominant Risk factor: prior thrombosis Platelet number is not a risk factor for thrombosis!!! Treatment: 🟢 Low-risk (<60 no clot) → Aspirin 🔴 High-risk (>60 +/- clot) → Cyto reduction (Hydroxyurea) ± anticoagulation Aspirin strategy: • JAK2+ (High risk of thrombosis) → twice daily • Others → once daily • CALR type 2 / triple-negative → may skip aspirin The "Triple-A" Score: Modern prognosis in ET now uses Absolute Neutrophil, Monocyte, and Lymphocyte counts to identify patients who will live as long as the general population. PV Management 🧪 Low-risk: 🩸 Phlebotomy + Aspirin 🎯 Hct <45% or Females <16, Males <16.5 High-risk: 💊 Hydroxyurea (Cytoreductive therapy-1L) 💊 Interferon (alternative) 💊 Ruxolitinib (2L- line-✅ Pruritis, 📉 Decreases EFS) 💊 Buslphan (Older patients ) New therapy: 💉 Ropeginterferon-alfa (FDA approval recently) 💉 Rusfertide – hepcidin mimetic (reduces phlebotomy) Myelofibrosis 🔥 → Most aggressive MPN. Night Sweats, 🌡️ Fever, 🦴 Bone Pain, Weight Loss,  Organomegaly  Hepatomegaly &  Splenomegaly),  Cytopenia, insomnia, fatigue, early satiety, abdominal pain 📊 IPSS Scoring System: Risk Groups 📉🧬Worsening prognosis: CALR+ (22.7%-17.7 yr)—>JAK2+ (65%-9.2yr) or MPL+ (4%-3.2yr)—> Triple Negative. (8.6%) 🚨High Molecular risk: 🧬IDH1/2, EZH2, ASXL1, SRSF2 Only cure: 🏥 Allogeneic stem cell transplant If not eligible: ->Low risk/not symptomatic: observation ->Low risk/symptomatic: clinical trial/ruxolitinib/peginterferon /hydroxyuria ->High risk: transplant elgible-allo HSCT 💊 JAK inhibitors 1. Ruxolitinib – best tolerated and for spleen size and constitutional symptoms- Side effects-Zoster, TB activation, avoid interruptions causes SIRS so bridge with steroids 2. Momelotinib (MF+Anemia)(SE-Peripheral neuropathies) – helpful for anemia 3. Fedratinib-2L (SE-GI, WE (monitor thiamine) 4. Pacritinib (ACVR1- MF + platelets <50k or anemia) ->No constitutuation symptoms/splenomegaly 1. EPO>500mIU/ml→Luspatercept, danzol, iMids 2. EPO<500mIU/ML→ESA ➡️ Improve symptoms & spleen ❌ Do not cure disease Emerging Therapies 🚀 • Navitoclax • Pelabresib • Selinexor -CAR-T, CALR vaccines, TGF-β inhibitors- are in development 🧬 Clonal Eosinophilia 🧪 Key Molecular Screens 1. FIP1L1–PDGFRA: 🧬 (~10% of HES). Detect via FISH (look for CHIC2 deletion) or RNA-Seq. 2. PDGFRB: 🧬Often an MDS/MPN overlap. 3. FGFR1: 🧬🔥 (8p11 syndrome). Highly aggressive; often transforms to AML/Lymphoma. 4. JAK2 Rearrangements: 🧬 (Not V617F mutation!). 💊 Targeted Treatment Table ->FIP1L1–PDGFRA- Imatinib- Exquisitely sensitive (100mg dose) ->PDGFRB- Imatinib - High response rates 👍 ->FGFR1- Pemigatinib -Requires Chemo + Transplant ->JAK2 Rearr-Ruxolitinib -Specific for rearrangements- CEL-NOSCytoreduction 📉Diagnosis of exclusion 🔍 Chronic Neutrophilic Leukemia (CNL) 🩸 Hallmark: CSF3R mutation (G-CSF receptor). 🧬🔗 Presentation: Neutrophils/Bands >80% + Splenomegaly Treatment: Ruxolitinib  (Symptom relief) ➡️ SCT 🏥 (Curative). Systemic Mastocytosis (SM) 🐝 Hallmark: KIT D816V mutation. 🧬 Physical Exam: Darier Sign (rubbing skin causes hives) 🤏+ Urticaria Pigmentosa. Markers: Tryptase 📈, CD25, and CD117 (KIT). 🧪 Treatment: Avapritinib or Midostaurin 🎯. #Hematology #Oncology #MedEd #HemOnc #FOAMed #MPN #BoardReview #MedStudentTwitter #InternalMedicine #Pathology #MPN @ASH_hematology @MPNVoice @ASCOPost @IMG_Oncologists @OncoAlert @oncodaily @realbowtiedoc @VJHemOnc @JCO_ASCO @LeukemiaJnl #HemOnc #MedTwitter #FOAMed @HemOncFellows

del(17p) vs TP53 mutation in CLL They are related but not identical. • 17p = chromosomal location • TP53 = gene • p53 = protein Both disrupt the p53 tumor-suppressor pathway and predict chemo resistance. Always test FISH + TP53 sequencing before therapy. #MVOnco #CLL #HemOnc

Disruptive Analysis of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Clinical and Therapeutic Distinctions Between Lowand Mid-Rectal Cancers @JCO_ASCO doi.org/10.1200/JCO-25… 👏excellent review 👉Adopting a location-specific, patient-centered approach is key @myESMO @ASCO