The genetic landscape and molecular subtypes of primary central nervous system lymphoma (PCNSL) remain inadequately characterized, presenting a major obstacle to the development of effective therapeutic strategies. We conducted a genomic study of 176 PCNSLs from five tertiary centers with long-term follow-up to expand the genomic landscape and identify new molecular subtypes. We first confirmed that the molecular subtyping of diffuse large B-cell lymphoma, as previously published, may not be fully applicable to Chinese PCNSL patients. We then identified (n = 58) and validated (n = 82) three prominent genetic subtypes related to different clinical and molecular features of PCNSL, and further confirmed by an independent external Chinese PCNSL cohort (n = 36). We called these BMIs (from the co-occurrence of mutations in two genes among BTG1, MYD88, and IRF4), which are associated with favorable outcomes; E3s (so-called EP300 mutations), which are associated with unfavorable outcomes; and UCs (unclassified, without characteristic mutations). Importantly, EP300 was mutated in more Asians (16.98%) than in Western PCNSLs (<4.53%), resulting in unfavorable outcomes independent of the specific mutation site. Our analysis comprehensively reveals the genomic landscape of Chinese PCNSL and emphasizes the clinical value of molecular classification for improving precision medicine strategies.

Clinical experience with cranial nerve palsy in

Venetoclax-based doublets with azacitidine or low dose cytarabine are the standard of care for the treatment of acute myeloid leukemia (AML) in older patients or those unfit for intensive chemotherapy. However, some patients do not attain complete remission, and over time, most patients relapse. Frontline triplet therapy incorporating a targeted therapy (FLT3, IDH or menin inhibitor) is an emerging treatment concept under investigation for this population. Initial triplet regimens have yielded encouraging composite complete remission and measurable residual disease negativity rates, enabling the transition to allogeneic stem cell transplantation for eligible patients. While effective, triplets are associated with myelosuppression and cytopenia-related toxicities, which can affect treatment tolerability and quality of life. In this review, we summarize the available evidence for triplet therapy in AML and offer our recommendations on the practical application of triplets in clinical practice, with particular focus on adjustments to dosing schedules in induction and continuation cycles. We also outline drug-specific adverse effects and interactions based on emerging clinical data to help guide the clinician, given the increasing use of novel combination therapies.

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Accumulation of genetic mutations in malignant myeloid precursor cells leads to an extremely poor prognosis for patients with acute myeloid leukemia (AML). Immunogenic neoantigens recognized by T cell receptor (TCR) can elicit effective immune responses against malignant cells with corresponding somatic mutations. To broaden the range of targeted treatments for AML, in this study, we explored the feasibility of immunotherapy targeting neoantigens arising from recurrent mutations, which are exclusively present on leukemic cells. We used data-driven methods to select seven neoantigens from four frequently mutated genes (NPM1, FLT3, TP53, and DNMT3A) associated with HLA-A*02:01-positive AML patients. Functional assays demonstrated that neoantigens derived from NPM1/W288fs, FLT3/D835H, and FLT3/D835Y were shown to induce specific T cell responses in AML patients. We further identified the specific TCR sequences from healthy donors capable of recognizing these neoantigens. In-depth studies of their specific T cells revealed the presence of dominant αβTCRs that could specifically recognize NPM1/W288fs and FLT3/D835H in an HLA-A*02:01-restricted manner. T cells engineered with each αβTCR selectively recognized and killed HLA-A*02:01-positive AML targets endogenously expressing corresponding mutations. Overall, our findings support the clinical translation of adoptive neoantigen-specific TCR-engineered T cells as a novel therapeutic strategy for treating AML.

Frontline high-dose therapy (HDT) is, in 2025, the standard of care for patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT). Prior to high-dose melphalan, induction therapy with quadruplet combinations is also proposed systematically when possible. Lenalidomide maintenance until progression is also recommended per international guidelines. This strategy has been developed over recent decades, based on results of phase 3 trials designed and conducted by different academic groups. With these therapeutic advances, the median overall survival (OS) for patients with MM has increased from 5 years in the 1990s, to over 15 years at present. Here, we present the contribution of the French myeloma cooperative group Intergroupe Francophone du Myélome (IFM) to these advances in the newly diagnosed transplant-eligible (NDTE) setting.