Tibsovo (ivosidenib) / CStone Pharma, Servier, Schrodinger, Sagard Healthcare - LARVOL DELTA

PyramIDH: A phase 3 study of ivosidenib monotherapy or azacitidine monotherapy in patients with mutant isocitrate dehydrogenase 1 myelodysplastic syndromes who have not received prior hypomethylating agent therapy (ASH 2025) - P1, P3 | "As of July 15, 2025, 34 sites are open for enrollment in 9 countries. In total, 19 patients have been prescreened, 4 have been screened, and 3 patients have been enrolled."

Clinical • Monotherapy • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • IDH1

Ivosidenib combined with venetoclax and azacitidine for the treatment of newly diagnosed IDH1-mutant Acute Myeloid Leukemia: A prospective, two cohorts, multicenter study (ASH 2025) - "Previous data showed that the multi-drug combination regimen of IVO demonstrates good tolerability and efficacy. This study will be the first to clarify the feasibility of multi-drug regimens in the treatment of IDH1m AML patients in China, providing ideas and evidence to improve the prognosis of Chinese IDH1m AML patients."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • IDH1

Real-world outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia treated with IDH1 and IDH2 inhibitors in the frontline setting (ASH 2025) - "Selective IDH1/2 inhibitors including ivosidenib (IDH1), olutasidenib (IDH1), and enasidenib (IDH2) are currently approved for IDH1/2-mutated (mIDH1/2) relapsed/refractory (r/r) acute myeloid leukemia; ivosidenib is also approved for mIDH1 r/r MDS based on clinical benefit observed in 18 patients on trial AG120-C-001...Patients previously treated with venetoclax (VEN) or a hypomethylating agent (HMA) were excluded... This study highlights safety and efficacy of IDH inhibitors, particularly among older adults with treatment-naïve MDS or CMML. Nearly half of our cohort were adults >80 years, a group often underrepresented in pivotal clinical trials. The overall response rate (CR + CRl + CRh) was 88.9% among 9 patients with BME; 50% of the entire cohort achieved PB-CR and median OS was 26 months."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • IDH1 • IDH2

Rhabdomyolysis in patients taking isocitrate dehydrogenase inhibitors for R/R Acute Myeloid Leukemia (ASH 2025) - "She was started on treatment with azacitidine, venetoclax, and magrolimab and achieved MRD-negative CR after cycle 1, then went on to complete 6 cycles of therapy, followed by 4 cycles of maintenance therapy with combination decitabine/cedazuridine and venetoclax prior to relapse. She was then treated with combination decitabine/cedazuridine, venetoclax, and ivosidenib...Azacitidine was discontinued after C33, at which time she continued on enasidenib monotherapy...She was on a stable dose of atorvastatin at the time of this event and had recently started azithromycin for symptoms of upper respiratory tract infection...al 2015). We hypothesize that rhabdomyolysis observed with IDH inhibitors may reflect a convergence of metabolic stressors, particularly in susceptible populations such as elderly patients with low muscle mass, and those on concomitant statins."

Clinical • Acute Myelogenous Leukemia • Brain Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Musculoskeletal Pain • Myelodysplastic Syndrome • Respiratory Diseases • Solid Tumor • Thrombocytopenia • IDH1 • IDH2

Ivosidenib with or without hypomethylating agent in IDH1-mutated AML: Real-world evidence to inform frontline therapy (ASH 2025) - "In the AGILE phase 3 trial, IVO combined with azacitidine significantly improved survival and remission rates. These results reinforce the importance of biomarker-driven therapies in informing treatment decisions and support the use of both regimens in routine clinical practice. They also highlight the need for larger, multi-source RWE studies to further characterize treatment outcomes and strengthen overall evidence."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Septic Shock • Thrombocytopenia • IDH1

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

A case of acute myeloid leukemia with isocitrate dehydrogenase 1 (IDH1) mutation treated with combination therapy, ivosidenib and azacitidine (ASH 2025) - "This case demonstrates the efficacy of Ivosidenib and Azacitidine in achieving remission in an older AML patient with an IDH1 mutation. As targeted therapies evolve, they provide promising alternatives for high-risk patients unable to tolerate intensive chemotherapy, improving survival"

Clinical • Combination therapy • Acute Myelogenous Leukemia • Constipation • Dermatology • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Solid Tumor • IDH1 • KIT

An investigation of somatic mutations in IDH genes in peripheral blood in the all of us research program (ASH 2025) - "In a general hospital setting, IDH somatic mutation rate was low. Myeloid malignancy or cytopenia were present in majority of the individuals with detected IDH mutations (VAF > 10%). Since IDH mutations can be targeted by ivosidenib or enasidenib, adequate hematological evaluation of individuals with incidental finding of these mutations and enrollment to clinical trials should be considered in the future guidelines."

Acute Myelogenous Leukemia • Autoimmune Hepatitis • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Hepatology • Immunology • Inflammatory Arthritis • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Rheumatoid Arthritis • Rheumatology • IDH1 • IDH2

Trial in progress: A phase II study of ziftomenib monotherapy in unfit patients with newly diagnosed Acute Myeloid Leukemia with NPM1 mutation or KMT2A rearrangement (ASH 2025) - P2 | "While the standard treatment for less intensive inductionin AML consists of venetoclax and azacitidine, some patients are too frail for this regimen and maybenefit from targeted therapies in the frontline setting. Currently, the only targeted treatment approvedas a single agent in the frontline setting is ivosidenib for patients aged 75 years and older with IDH1-mutated AML, based on an open-label, single arm study...If at least 3patients achieve CR/CRh of these 18 patients, an additional 11 patients will be enrolled. For the NPM1-mcohort, if 2 patients achieve CR/CRh of an initial 10 patients, then 12 additional patients will be enrolled."

Clinical • Monotherapy • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • IDH1 • KMT2A • NPM1

Trial in progress – a phase 1b trial of ivosidenib combined with ruxolitinib in IDH1-mutated advanced myeloproliferative neoplasms (ASH 2025) - P1 | "For patientswith ≥5% blasts the response will be characterized using 2012 MPN-BP criteria (Mascarenhas et al, LeukRes 2012); for patients with MF and ≤5% blasts the response will be characterized using 2013International Working Group-Myelofibrosis Research Treatment/European LeukemiaNet revisedresponse criteria. Exploratory endpoints include characterization of co-occurring pathogenic mutations,evaluation of measurable residual disease (MRD status) via error-corrected next generation sequencing,assessment of the proportion of patients going onto allogeneic stem cell transplant, and assessment ofclonal dynamics under combined IDH1/JAK2 inhibition."

Metastases • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • IDH1 • IDH2

A multiarm phase 1b study of personalized oral maintenance therapy with decitabine/cedazuridine (ASTX727) plus physician's choice of venetoclax, gilteritinib, enasidenib, or ivosidenib in Acute Myeloid Leukemia (ASH 2025) - P1 | "Pts were required to have received at least 2 courses of intensive chemotherapy(intermediate to high-dose cytarabine-based) or 3 courses of low-intensity therapy (HMA or low-dosecytarabine-based) prior to enrollment. Personalized fully oral maintenance therapy is feasible in AML. Myelosuppression andinfections were the most common adverse events. Further enrollment and follow-up is needed toevaluate efficacy."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • TP53

Phase 3 Study of ivosidenib (IVO) and azacitidine (AZA) with or without venetoclax in adult patients with newly diagnosed IDH1-mutated AML or MDS/AML ineligible for intensive chemotherapy (EVOLVE-1) (ASH 2025) - P3 | "Secondary endpoints include overall survival (OS),rates of complete remission (CR) and CR with partial hematologic recovery (CRh), duration of response,transfusion independence rate, and quality of life. Exploratory endpoints include quality of life,cumulative incidence of relapse (CIR), cumulative incidence of death (CID).The global trial is expected to begin enrollment by Aug 2025."

Clinical • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • IDH1

Healthcare resource utilization and cost of molecular targeted versus non-targeted therapies in acute myeloid leukemia (ASH 2025) - "We examined AML-related HCRU and costs over a 12-month period following treatment initiation.Patients were categorized into two sub-cohorts: (1) those receiving MTT (ivosidenib, enasidenib,midostaurin, gilteritinib) and (2) biomarker-positive patients (IDH1, IDH2, FLT3) treated only with non-MTT. For AML patients with actionable molecular mutations, treatment with MTTs results inreduced healthcare utilization but increased total costs, primarily due to drug expenses. These findingsemphasize the economic trade-offs in precision oncology and highlight the necessity for strategies toenhance the cost-effectiveness of MTTs in routine care."

HEOR • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • IDH1 • IDH2

Updated response and safety analyses from a Phase 1 study of ivosidenib combined with intensive chemotherapy in patients with newly diagnosed (ND) Acute Myeloid Leukemia with isocitrate dehydrogenase (IDH)1 mutation (ASH 2025) - P1, P3 | "Introduction Ivosidenib (IVO) is approved as monotherapy and in combination with azacitidine for frontline treatmentof patients (pts) with mIDH1 acute myeloid leukemia (AML) unfit for intensive chemotherapy (chemo)...Pts with ND mIDH1AML received induction therapy: cytarabine 200 mg/m2/d × 7 d and either daunorubicin 60 mg/m2/d oridarubicin 12 mg/m2/d × 3 d (up to 2 cycles of induction were permitted) and IVO 500 mg once dailystarting on d 1 of induction therapy...IVO maintenance has an acceptable safety profile, is associated with stablenormalization of blood counts, and results in durable responses and long-term survival acrosscomutational profiles. The benefit of this frontline regimen is being assessed in a phase 3 randomized,blinded trial (NCT03839771)."

Clinical • P1 data • Acute Kidney Injury • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Renal Disease • Thrombocytopenia • TP53

A randomized Phase II trial of ASTX727 and venetoclax with or without enasidenib for newly diagnosed older adults with IDH2 mutant Acute Myeloid Leukemia: A myelomatch substudy (MM1OA-S03) (ASH 2025) - P2 | "In IDH1 mutant AML, a phase 1btrial of the combination of the IDH1 inhibitor ivosidenib with venetoclax and azacitidine resulted in anoverall response rate of 94% with MRD negativity achieved in 77%, without any patients discontinuingtherapy due to intolerance. The study wasactivated on April 1, 2025 and is expected to continue until October 2027. Funding: Funding: NIH/NCI grants U10CA180888, U10CA180819"

Clinical • P2 data • Acute Myelogenous Leukemia • Multiple Myeloma • IDH1 • IDH2

Ivosidenib in refractory or relapsed IDH1-mutated Acute Myeloid Leukemia patients in real life settings: The ivoobs observational study from the french AML intergroup ALFA/filo (ASH 2025) - P | "Median number of previous lines prior IVO onset were 1 [IQR:1-3]; 82 patients (67%) receivedintensive chemotherapy as first line,36 (29% ) were pre-exposed to VEN prior IVO initiation, while 20(15.8%) patients received IVO as post hematopoietic stem cell transplantation (HSCT) salvage treatment.93 patients received IVO monotherapy, 26 in combination with azacitidine (AZA) and 8 with venetoclax(VEN) +/- AZA (defined as AZA/IVO (+/-VEN) group) Most frequent co-mutations were NPM1 (32%), RUNX1(23%), ASXL1 (21%) and BCOR (18%). Inmultivariate analysis, only higher platelets (HR=0.96, p=0.015) and HU use (HR=2.95, p<.001) wereindependently associated with OS.Conclusion In this real-life study, IVO compares favourably with previously reported prospective studies in R/Rsettings, with a manageable safety profile. HU use for proliferative disease at IVO onset is associated witha lower response rate and inferior outcome."

Clinical • Observational data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • ASXL1 • BCOR • IDH1 • NPM1 • RUNX1

ALIDHE: An ongoing open-label phase 3b study investigating ivosidenib with azacitidine in clinical practice in adult patients with newly diagnosed mutant isocitrate dehydrogenase 1 (mIDH1) Acute Myeloid Leukemia (AML) ineligible for intensive induction chemotherapy (IC) (ASH 2025) - P3 | "The data will enrich knowledge on theIVO+AZA safety profile and help translate efficacy to effectiveness, bridging the gap between clinical trialsand clinical practice, fulfilling the objectives of this real-world postapproval study. The study is stillenrolling; future analyses will focus on effectiveness and QOL."

Clinical • P3 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • ASXL1 • CEBPA • DNMT3A • IDH1 • JAK2 • NPM1 • RUNX1 • SRSF2 • STAG2 • TET2 • TP53 • U2AF1

CYP3A4 inhibitors (CYP3A4i) and myelosuppression in patients (Pts) with newly diagnosed mutant isocitrate dehydrogenase 1 (mIDH1) Acute Myeloid Leukemia (AML) in the phase 3 AGILE study (ASH 2025) - P3 | "Introduction Ivosidenib (IVO) is an oral, targeted, small-molecule inhibitor of mIDH1 approved for the treatment of ptswith mIDH1 AML. In the pivotal AGILE study of IVO in combination with azacitidine (AZA) in newlydiagnosed AML (NCT03173248), the most common grade ≥3 adverse events (AEs) were hematologic inboth the IVO+AZA and placebo (PBO)+AZA arms (Montesinos, NEJM 2022)...Forexample, venetoclax requires dose reduction when administered concomitantly with CYP3A4i, yetincreased exposure and myelosuppression still occur (Kawedia, AJH 2025)...Population PK modeling predicted theAUC of IVO at SS to increase moderately (<2-fold) when coadministered with voriconazole, fluconazole,and posaconazole—by 48.7%, 60.8%, and 58.8%, respectively—compared with IVO alone...However, low rates of individual AEs limit the ability to draw firm conclusions.IVO exposure was predicted to increase <2-fold when given in combination with moderate/strongCYP3A4i. As concomitant use of..."

Clinical • P3 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia • CYP3A4 • IDH1 • TINCR

Trial in progress - a randomized study of ASTX727 with or without Iadademstat in accelerated/blast-phase myeloproliferative neoplasms (ASH 2025) - P2 | "Outcomes were similar in patients treated with intensivechemotherapy, DNA methyltransferase inhibitor (DNMTi) + venetoclax-based therapy, and other DNMTi-based approaches (Patel et al, Blood Adv 2024)...The oral LSD1 inhibitor iadademstat has been studiedin combination with the DNMTi azacitidine in de novo acute myeloid leukemia (AML) in the context of thePhase II ALICE study; the complete remission (CR)/complete remission with incomplete count recovery(CRi) rate was 52%...Exclusion criteria of note include IDH1-mutatedMPN-BP (due to the availability of ivosidenib as an approved frontline therapy).The dose escalation phase will follow a 3+3 design...Secondary endpoints include event-free survival, overall survival, and percentage of patients that go onto allogeneic stem celltransplantation. Exploratory endpoints include concordance of response between EuropeanLeukemiaNet (ELN) 2022 response criteria (Dohner et al, Blood 2022) and 2012 MPN-BP criteria,assessment of..."

Clinical • Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • ASXL1 • IDH1 • IDH2 • TP53

Real-world overall survival in patients with Acute Myeloid Leukemia treated with ivosidenib plus azacitidine in the USA: Trinetx-based analysis (ASH 2025) - "As a comparison cohort, results from patients treated with venetoclax + AZA (VEN+AZA) werealso retrieved from the same TriNetX database. Results from thosetreated with VEN+AZA were consistent with results from the VIALE-A study. These preliminary findingssupport the utility of IVO+AZA in clinical practice, but further real-world evidence generation is warranted,including within the framework of REAL-IDH."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • IDH1

Real-world survival of IDH-mutant patients in China before IDH-inhibitor era: A multicenter retrospective study from anhui cooperative hematology group(ACHG) (ASH 2025) - "The medianage of IDH1mut and IDH2mut patients at the time of diagnosis is 59.2 and 59.5 years, respectively, whichwas statistically older to IDHwt patients (50.9 years, p<0.05).After the first induction therapy, which mainly include cytarabine based intensive chemotherapy andazacitidine plus venetoclax treatment, 64.8%, 52.4%, and 55.4% of patients in the IDHwt, IDH1mut, andIDH2mut groups, respectively, have achieved complete remission (CR). Azacitidine plus venetoclax treatment improve the survival of IDH1mut patients to thesame level as other patients with IDH2mut and IDHwt. Given the AGILE study of azacitidine plus ivosidenibin newly diagnosed IDH1-mutated AML shows a longer median OS (29.3 months), we recommend thatIDH1mut patients who are unable to access IDH1 inhibitors consider venetoclax-based treatment as apotential strategy to enhance survival outcomes."

Real-world • Real-world evidence • Retrospective data • Hematological Disorders • IDH1 • IDH2

Impact of social determinants of health on access to molecular targeted therapy in AML and MDS: A real-world analysis (ASH 2025) - "MTTwas defined as receiving ivosidenib (IDH1), enasidenib (IDH2), or midostaurin/gilteritinib (FLT3) for bothcohorts.We evaluated eleven SDOH domains: unemployment, financial strain, food insecurity, housing instability,interpersonal safety concerns, low educational attainment, mental health disorders, physical inactivity,poor access to care, substance use, and transportation barriers. The modest association betweenfinancial strain and therapy receipt in AML warrants further investigation but was not observed in MDS.These findings suggest that system-level barriers, such as institutional protocols, clinician practices, andpayer dynamics, may play a more substantial role in driving disparities in precision oncology. Futureresearch should prioritize identifying and addressing these structural impediments to promote broadand consistent access to molecular testing and targeted therapies for individuals with myeloidmalignancies."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3 • IDH1 • IDH2 • SF3B1

IDH1/2-mutant clonal hematopoiesis: A novel driver of autoinflammatory disease (ASH 2025) - P2 | "We used data from three CCUS cohorts:first, a multi-institutional cohort of CCUS patients with systemic autoinflammatory disease (SAID) whowere UBA1-negative, second, a hospital-based cohort at Mayo Clinic, and third, a cohort of IDH1 carriersenrolled on a phase II clinical trial of ivosidenib (NCT05030441)...IDH inhibition demonstrates efficacy for improving inflammatory manifestationswithin an ongoing clinical trial. Together these results nominate IDH mutant CH as a driver ofautoimmune diseases with therapeutic implications."

Bone Marrow Transplantation • Dermatology • Giant Cell Arteritis • Hematological Disorders • Hematological Malignancies • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Rheumatoid Arthritis • Sjogren's Syndrome • CRP • IDH1 • IDH2

IDH mutant MDS: Proposal for disease subset recognition based on molecular and clinical features, and the availability of targeted therapies (ASH 2025) - "For example, del5q MDS accounts for <5% of MDS, but the impact of lenalidomide treatmentemphasizes the need to identify those patients (pts)...Reponses to azacitidine were higher among IDH1 & 2 MT pts compared to WT (ORR (CR+PR+HI) 49.1%,48.1%, and 37.5%, respectively, and CR was 14.3%, 14% and 10.4%, respectively) (p=0.024 compared toWT and p=1.0 between IDH1 & 2).Among IDH1 MT pts, 16 pts received ivosidenib at any timepoint including AML...Three ptsreceived olutasidenib after ivosidenib, no response was observed.Among IDH2 MT pts, 42 received enasidenib at any timepoint including AML...Treatment with IDH inhibitors during the disease coursesuggests survival benefit among those pts. Our findings suggest the recognition of IDH MT MDS as aunique disease subset."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • ASXL1 • IDH1 • IDH2 • RUNX1 • SF3B1 • SRSF2 • TET2 • TP53

Ivosidenib leads to durable responses in IDH1 mutated clonal cytopenias of undetermined significance: A phase II decentralized clinical trial (ASH 2025) - "Decentralized trials represent a feasible solution for the conduct of clinical trials in rarehematologic neoplasms and precursor conditions. Ivosidenib was well-tolerated and induced durablehematologic remissions in IDH1-mutant CCUS. Most pts showed a reduction in clonal burden withmutation clearance commonly seen with long-term treatment demonstrating that ivosidenib modifies thenatural history of IDH1-mutant CCUS."

Clinical • Decentralised clinical trial • P2 data • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Septic Shock • Thrombocytopenia • IDH1 • TMB