Revumenib

MD Anderson researchers investigated the gut microbiome, lung adenocarcinoma genesis, and tested new therapies. Highlights include a bean diet improving gut microbiome balance, durvalumab and olaparib reducing endometrial cancer risk, novel leukemia therapies, IL-17 research, ELI-002 vaccine for KRAS-mutated cancers, a lung cancer pre-cancer atlas, saruparib for breast cancer, nivolumab reducing lung cancer relapse, proton therapy for head and neck cancer, GPX4 co-inhibition overcoming PARP resistance, and CD28 costimulation enhancing CAR NK cell efficacy.

MSKCC advanced cancer treatments in 2024 include new surgical techniques, vaccines, drugs enhancing radiation, and diagnostic tools. The FDA approved 11 drugs based on MSK's pivotal clinical trials, covering new uses for existing drugs, effective drug combinations, engineered cell therapies, and novel targeted therapies. Key developments include a KRAS vaccine for pancreatic and colorectal cancer, combination drug-radiation treatment for basal cell carcinoma, noninvasive E-nose for lung cancer detection, improved transplant success with partially matched donors, exercise impact on prostate cancer biomarkers, new imaging for lung and prostate cancers, TIL therapy for non-small cell lung cancer, robotic neurosurgery for spinal tumors, avoiding surgery for HPV throat cancer with innovative radiation, imlunestrant for ER+, HER2- advanced breast cancer, mRNA vaccine for pancreatic cancer, and immunotherapy for rectal cancer. FDA approvals included tepotinib for METex14 lung cancer, CAR T treatment for mantle cell lymphoma, selpercatinib for RET-linked thyroid cancer, repotrectinib for NTRK fusion cancers, adagrasib with cetuximab for KRAS-G12C colorectal cancer, afamitresgene autoleucel for synovial sarcoma, vorasidenib for IDH glioma, inavolisib with fulvestrant and palbociclib for breast cancer, revumenib for KMT2A leukemia, zanidatamab for HER2 biliary tract cancer, and zenocutuzumab for NRG1 fusion pancreatic and lung cancers.

David Stan, diagnosed with acute myeloid leukemia in 2023, faced treatment failure locally. His family found hope in a clinical trial at MD Anderson using a menin inhibitor, leading to full remission and a stem cell transplant. Despite side effects, David is now in full remission and considering a career in medicine.

Revumenib (Revuforj) received FDA approval in Nov 2024 for KMT2A-rearranged relapsed/refractory acute leukemia, based on AUGMENT-101 study showing 21.2% CR/CRh rate. 14% achieved transfusion independence, highlighting potential to improve remission rates and quality of life. Revumenib's ability to clear blasts offers patients opportunity for allogeneic stem cell transplant.

2024 saw significant advances in cancer research, including personalized neoantigen vaccines, AI in drug discovery, and first-in-class therapeutics. Progress was also made in early detection, overcoming resistance, and addressing cancer health disparities.

Three clinical trials from MD Anderson Cancer Center showed significant results with novel triplet therapies for leukemias. The SAVE trial achieved an 82% response rate in advanced AML with KMT2A or NUP98 rearrangements. The IDH1-mutant AML trial showed a 94% overall response rate. The CLL trial achieved 98% undetectable MRD in bone marrow and 100% in blood after 13 cycles.

Three clinical trials from MD Anderson Cancer Center showed significant results with novel triplet therapies for leukemias. The SAVE trial with revumenib, ASTX727, and venetoclax achieved an 82% overall response rate in relapsed/refractory AML patients with KMT2A or NUP98 rearrangements. A triplet regimen of ivosidenib, venetoclax, and azacitidine showed 94% overall response and 93% composite complete remission in IDH1-mutant AML. A pirtobrutinib, obinutuzumab, and venetoclax triplet achieved 98% undetectable MRD in previously untreated CLL patients.

Revumenib showed a 63.9% overall response rate in relapsed/refractory KMT2Ar acute leukemia, with manageable safety and no discontinuations due to differentiation syndrome or QTc prolongation. Median duration of response was 6.4 months, and 33.9% of patients proceeded to hematopoietic stem cell transplant.

Revumenib showed continued clinically meaningful responses, including higher MRD-negativity rates and progression to HSCT, in patients with relapsed or refractory KMT2Ar acute leukemia. The safety profile remained manageable, with no discontinuations due to differentiation syndrome or QTc prolongation. The overall response rate was 63.9%, with 22.7% achieving CR or CRh and 42.3% achieving CRc. Median duration of response was 6.4 months, and 33.9% proceeded to HSCT. No new safety signals were reported.