---
title: "Selinexor plus R-CHOP Yields High Response in Newly Diagnosed Double/Triple‑Hit Lymphoma"
id: "pubmed-42480213"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42480213"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42480213/"
doi: "10.1182/bloodadvances.2025018580"
published_at: "2026-09-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Selinexor plus R-CHOP Yields High Response in Newly Diagnosed Double/Triple‑Hit Lymphoma
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42480213
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42480213/)
- **DOI:** [10.1182/bloodadvances.2025018580](https://doi.org/10.1182%2Fbloodadvances.2025018580)
- **Published At:** 2026-09-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This single-arm, prospective phase 2 trial evaluated **selinexor** added to **R-CHOP** (S-RCHOP) as first-line therapy for newly diagnosed **double-hit lymphoma (DHL)** and **triple-hit lymphoma (THL)**. The study enrolled 13 patients between May 2022 and August 2024. - Treatment schema: up to six 21-day cycles of S-RCHOP with selinexor 60 mg given on days 1, 8, and 15 of each cycle. The chemotherapy backbone was standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). - Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), 2-year central nervous system (CNS) relapse rate, and adverse events (AEs). Exploratory analyses included next-generation sequencing (NGS) and circulating cell-free DNA (**cfDNA**) monitoring. - Efficacy: ORR was 100% (complete response [CR] 76.9%, partial response 23.1%). At a median follow-up of 25.4 months, 2-year PFS was 67.7% and 2-year OS was 67.1%. One patient experienced CNS relapse within the study period. - Safety: Hematologic toxicities were common. The most frequent all-grade AEs reported were leukopenia and neutropenia (55.1% each), febrile neutropenia and fatigue (43.5% each), and thrombocytopenia (33.7%). - Molecular findings: NGS and baseline cfDNA showed frequent **BCL6** and **IGLL5** mutations across patients. Posttreatment **cfDNA** became negative in 72.7% of patients; all cfDNA‑negative patients were in CR by PET‑CT. - Interpretation: S-RCHOP produced high response rates in this small DHL/THL cohort but was associated with frequent hematologic AEs. The authors highlight the value of **cfDNA** for monitoring and recommend further study of XPO1 inhibition with R-CHOP, prioritizing dose optimization. - Limitations and next steps: This report is preliminary and based on 13 patients; further investigation in larger cohorts and formal dose-finding were recommended by the authors. Details beyond what is reported in the abstract (such as full toxicity grading, dose modifications, or long-term outcomes) were not provided in the source abstract.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42480213/#linkout) Title & authors Abstract Conflict of interest statement Figures Similar articles References Publication types MeSH terms Substances Associated data Related information LinkOut - more resources Clinical Trial Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42480213/) . 2026 Sep 22;10(18):6236-6246. doi: 10.1182/bloodadvances.2025018580. # Selinexor combined with R-CHOP achieved a high response rate in newly diagnosed double/triple-hit lymphoma [Cong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+C&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Xi Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+X&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Jieyu Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+J&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Tao Lei](https://pubmed.ncbi.nlm.nih.gov/?term=Lei+T&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Haifeng Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+H&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Shuailing Peng](https://pubmed.ncbi.nlm.nih.gov/?term=Peng+S&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Shuiyun Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+S&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Haiyan Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+H&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#full-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.") Affiliations Expand ### Affiliation * 1 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China. * PMID: **42480213** * PMCID: [ PMC13584109 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13584109/) * DOI: [ 10.1182/bloodadvances.2025018580 ](https://doi.org/10.1182/bloodadvances.2025018580) Item in Clipboard Clinical Trial # Selinexor combined with R-CHOP achieved a high response rate in newly diagnosed double/triple-hit lymphoma Cong Li et al. Blood Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42480213/) . 2026 Sep 22;10(18):6236-6246. doi: 10.1182/bloodadvances.2025018580. ### Authors [Cong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+C&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Xi Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+X&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Jieyu Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+J&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Tao Lei](https://pubmed.ncbi.nlm.nih.gov/?term=Lei+T&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Haifeng Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+H&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Shuailing Peng](https://pubmed.ncbi.nlm.nih.gov/?term=Peng+S&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Shuiyun Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+S&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China."), [Haiyan Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+H&cauthor_id=42480213)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42480213/#short-view-affiliation-1 "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.") ### Affiliation * 1 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China. * PMID: **42480213** * PMCID: [ PMC13584109 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13584109/) * DOI: [ 10.1182/bloodadvances.2025018580 ](https://doi.org/10.1182/bloodadvances.2025018580) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Double-hit lymphoma (DHL) and triple-hit lymphoma (THL) are aggressive subtypes of high-grade B-cell lymphoma with poor prognosis. This study evaluated the efficacy and safety of selinexor, a first-in-class oral inhibitor of exportin 1 (XPO1), combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; S-RCHOP) as first-line therapy for DHL/THL. This single-arm, prospective phase 2 study enrolled 13 patients from May 2022 to August 2024. Patients received up to 6 21-day cycles of S-RCHOP (selinexor 60 mg on days 1, 8, 15). The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), central nervous system (CNS) relapse rate within 2 years, and adverse events (AEs). Exploratory analyses included next-generation sequencing (NGS) and circulating cell-free DNA (cfDNA) monitoring. Thirteen patients (9 DHL and 4 THL) were enrolled. ORR was 100% (complete response [CR], 76.9%; partial response, 23.1%). At a median follow-up of 25.4 months, the 2-year PFS and OS were 67.7% and 67.1%, respectively. One patient developed CNS relapse. The most common all-grade AEs included leukopenia and neutropenia (55.1% each), febrile neutropenia and fatigue (43.5% each), and thrombocytopenia (33.7%). NGS and cfDNA revealed frequent BCL6 and IGLL5 mutations. Posttreatment cfDNA negativity was achieved in 72.7% of patients, all of whom were in CR by positron emission tomography-computed tomography. In this study, S-RCHOP achieved high response rates in DHL/THL but was associated with frequent hematologic AEs. cfDNA monitoring provided valuable insights into treatment response. These preliminary findings support further investigation of XPO1 inhibition combined with R-CHOP, with priority given to dose optimization. This trial was registered at www.clinicaltrials.gov as [NCT05974085](http://clinicaltrials.gov/show/NCT05974085 "See in ClinicalTrials.gov"). © 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Conflict-of-interest disclosure: The authors declare no competing financial interests. ## Figures [ ![None](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/c117c2172196/BLOODA_ADV-2025-018580-ga1.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/f863b0629830/BLOODA_ADV-2025-018580-ga1.webp) ** Graphical abstract ** ** Graphical abstract ** **Graphical abstract** [ ![Figure 1.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/b3c99a34df87/BLOODA_ADV-2025-018580-gr1.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/10069eefed90/BLOODA_ADV-2025-018580-gr1.webp) ** Figure 1. ** **Swimmer plot illustrating the treatment…** ** Figure 1. ** **Swimmer plot illustrating the treatment response characteristics of 13 patients included in this…** **Figure 1.** **Swimmer plot illustrating the treatment response characteristics of 13 patients included in this study.** First response (day 42) was assessed by CT; second response (day 84) and final response (day 126) were assessed by PET-CT. PET-CT, positron-emission tomography–CT. [ ![Figure 2.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/7d1cf1b037a3/BLOODA_ADV-2025-018580-gr2.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/2711632a3cb1/BLOODA_ADV-2025-018580-gr2.webp) ** Figure 2. ** **Kaplan-Meier curves.** (A) PFS. (B)… ** Figure 2. ** **Kaplan-Meier curves.** (A) PFS. (B) OS. **Figure 2.** **Kaplan-Meier curves.** (A) PFS. (B) OS. [ ![Figure 3.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/dcb3c9d9725e/BLOODA_ADV-2025-018580-gr3.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/5b6c32785798/BLOODA_ADV-2025-018580-gr3.webp) ** Figure 3. ** **Gene mutation frequencies of NGS…** ** Figure 3. ** **Gene mutation frequencies of NGS and pretreatment cfDNA of all 13 patients.** Only… **Figure 3.** **Gene mutation frequencies of NGS and pretreatment cfDNA of all 13 patients.** Only gene mutations observed in both NGS and cfDNA are listed. [ ![Figure 4.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/a9969f620133/BLOODA_ADV-2025-018580-gr4.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/60a352c07a31/BLOODA_ADV-2025-018580-gr4.webp) ** Figure 4. ** **Heat map of somatic mutations…** ** Figure 4. ** **Heat map of somatic mutations detected in baseline cfDNA and their relationship with…** **Figure 4.** **Heat map of somatic mutations detected in baseline cfDNA and their relationship with clinicopathological features in 13 patients.** Each column represents 1 patient (numbers 1-13); each row corresponds to a sequenced gene or clinicopathological features. A filled box indicates the presence of a mutation, with the color intensity reflecting the gene mutation frequency across the cohort (red gradient). Clinical annotations (colored bars) include age (≤60 vs >60 years), COO subtype (GCB vs non-GCB), DH/TH status (MYC/BCL2 vs MYC/BCL6 vs TH), Ann Arbor stage (I-II vs III-IV), IPI score (0-1 vs 2-3 vs 4-5), best response to S-RCHOP therapy (CR vs PR), and sex (male vs female). The diagram allows a visual exploration of the possible associations between baseline genomic alterations and established prognostic variables. COO, cell of origin; DH, double hit; TH, triple hit. [ ![Figure 5.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/d612b5d829d8/BLOODA_ADV-2025-018580-gr5.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f0/13584109/41594d6c1509/BLOODA_ADV-2025-018580-gr5.webp) ** Figure 5. ** **Changes in the number of…** ** Figure 5. ** **Changes in the number of gene mutations detected in circulating cfDNA in 13…** **Figure 5.** **Changes in the number of gene mutations detected in circulating cfDNA in 13 patients with DHL/THL at different time points.** The x-axis indicates the timing of peripheral blood sample collection: pretreatment and CR/PR. The y-axis represents the number of gene mutations. Each colored line represents an individual patient (patients 1-13). Most patients showed a decrease in gene mutation burden after treatment response. [See this image and copyright information in PMC](https://pubmed.ncbi.nlm.nih.gov/42480213/) ## Similar articles * [ Zanubrutinib, lenalidomide and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as initial treatment in non-germinal center B-cell diffuse large B-cell lymphoma: a multi-center phase 2 study by Jiangsu Cooperative Lymphoma Group (JCLG). ](https://pubmed.ncbi.nlm.nih.gov/41136989/) Xia Y, Miao Y, Qian S, Zhang R, Qin S, Xie X, Li B, Sha Y, Tang H, Jin H, Cao L, Xu W, Fan L, Li J, Shi W, Zhu H.Xia Y, et al.BMC Med. 2025 Oct 24;23(1):583. doi: 10.1186/s12916-025-04418-y.BMC Med. 2025.PMID: 4113
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