Revumenib

Blinatumomab (Blincyto) has significantly expanded its role in treating B-cell precursor acute lymphoblastic leukemia (B-ALL) since 2014, becoming a standard in consolidation regimens for both adults and children, regardless of MRD status. FDA approval in June 2024 for CD19-positive, Ph-negative B-ALL was based on the ECOG-ACRIN E1910 study, showing improved survival rates. Its use now extends beyond adults, integrating into pediatric-inspired regimens, marking a shift in B-ALL treatment paradigms.

Revuforj (revumenib), a first-in-class menin inhibitor, was FDA approved on November 15, 2024, for treating relapsed or refractory acute leukemia with KMT2A translocation in patients aged 1 year and older. It blocks KMT2A and KMT2A fusion proteins' interaction with menin. Approved based on AUGMENT-101 trial data showing a 21.2% CR+CRh rate. Administered orally, it carries a Boxed Warning for differentiation syndrome and has common adverse reactions including hemorrhage and nausea.

In 2024, the FDA approved over 60 oncology therapies, including 11 first-in-class drugs. Highlights include Revumenib and Zolbetuximab for leukemia and gastric cancer, respectively, and new treatments targeting HER2, PD-L1, and ALK with improved efficacy and reduced toxicity. The approvals also featured novel strategies like bispecific antibodies and CAR T-cell therapies, alongside new indications for existing drugs.

In 2024, the FDA approved 50 new drugs, focusing on cancer, with 15 approvals. Small molecules led with 32 approvals, followed by proteins and oligonucleotides. Notable approvals included a schizophrenia treatment and a NASH drug, marking significant advancements in therapeutic areas.

The SAVE study showed high remission rates with all-oral revumenib, decitabine/cedazuridine, and venetoclax in relapsed/refractory AML patients, particularly those with KMT2Ar, NPM1mt, and NUP98r. The overall response rate was 82%, with 48% achieving complete remission. MRD negativity was observed in 65% of responders. Common adverse events included febrile neutropenia and lung infection. The study aims to improve responses and reduce relapse risk in AML patients.

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.