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Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71–4.56; p?

Background:Hydroxyurea (HU) is the most commonly used first-line cytoreductive treatment option for patients with myeloproliferative neoplasms (MPN) worldwide. However, increasing evidence on the efficacy and safety of pegylated interferon-alpha2 (IFNα) is emerging, and optimal first-line treatment is to be established.

Background:Glofitamab (Glofit) is a CD20xCD3 bispecific antibody which engages and redirects T cells to eliminate B cells. Glofit monotherapy recently received FDA and EMA approval for treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 prior lines of therapy. Polatuzumab vedotin (Pola) is a CD79b-targeted antibody-drug conjugate that has a complementary mode of action to Glofit, with little toxicity overlap. In this open-label, multicenter Phase Ib/II study (NCT03533283), Glofit+Pola demonstrated durable responses and a manageable safety profile in patients with R/R DLBCL (Hutchings et al. ICML 2023). We present updated results with longer follow-up in patients with R/R DLBCL, including high-grade B-cell lymphoma (HGBCL), and in patients with prior chimeric antigen receptor (CAR) T-cell therapy.

Introduction:Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) who are ineligible for intensive chemotherapy and autologous stem cell transplantation have limited therapeutic options and poor prognosis, and there is an unmet need for new therapeutic alternatives in this situation. Based on gene expression profiling, DLBCL can be divided into the germinal centre B-cell (GCB) and the activated B-cell (ABC) subtype. These subtypes are dependent on different oncogenic pathways and may differ in responsiveness to targeted therapies. Idelalisib is a small-molecule inhibitor of PI3Kδ, currently approved for treatment of follicular lymphoma and CLL. Based on the high response rate of idelalisib in heavily pretreated patients with indolent B-cell lymphomas, among whom many may have undetected transformed disease, we hypothesized that idelalisib may also be active in r/r DLBCL, particularly in the GCB subtype, due to frequent PTENloss and unregulated activation of PI3K signaling in this subtype. Here, we evaluated the efficacy and safety of idelalisib as a single agent therapy in patients with r/r DLBCL in a multi-centre phase II non-randomized trial. To our knowledge, this is the first prospective study on the use of single agent idelalisib in patients with DLBCL.

El-Galaly: Roche: Consultancy, Other: travel funding. Cheah:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Speaker's Bureau. Kansara:Celgene: Honoraria. Connors:Bristol Myers Squib: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Millennium Takeda: Research Funding; Seattle Genetics: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Seymour:Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding.

Leppa: Roche: Honoraria, Other: Travel expenses, Research Funding; Janssen: Research Funding; Bayer: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Other: Travel expenses; CTI Life Sciences: Honoraria; Merck: Other: Travel expenses. Joergensen:Amgen: Research Funding; Mundipharma: Research Funding. Mannisto:SOBI: Honoraria; Pfizer: Honoraria; Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses. Jerkeman:Gilead: Research Funding; Celgene: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Holte:Amgen: Research Funding; Mundipharma: Research Funding.

Background:Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically <6 months. However, data in patients that develop SCNS following primary therapy that contains a rituximab-based-regimen as well as the impact of more intensified treatment for SCNS are limited.

Introduction:Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of early central nervous system (CNS) progression is high. Here we present the final results from a Nordic phase II study, where dose-dense chemoimmunotherapy including early systemic CNS prophylaxis with high dose methotrexate (HD-Mtx), further intensified by intrathecally (IT) administered liposomal cytosine arabinoside (AraC), was given.

Introduction: The JAK2 V617F mutation is believed to occur in an early stem cell. Analysis of the JAK2 mutational status of patients suspected of a chronic myeloproliferative disorder has already been widely introduced into the diagnostic procedure. The ability to determine the size of the mutated clone and to monitor its evolution over time would be of great interest. Most methods are based on sequencing and qualitative or semi-quantitative PCR methods with limited sensitivity We present a highly sensitive real-time quantitative PCR assay, and have determined the percentage of mutated alleles in granulocytes, monocytes, T-lymphocytes and B-lymphocytes. Methods: Peripheral blood from 13 patients (PV=10, IMF=2, ET=1) with a known JAK2 mutation was collected. CD66-FITC, CD14-PE-Cy7, CD19-PE and CD3-APC were used to label granulocytes, monocytes, B-lymphocytes and T-lymphocytes, respectively. The cells were collected by a four-way FACS sort with a specificity of 99%. DNA was extracted by standard procedure. A real-time quantitative assay with a common forward primer, a Taqman probe and a wildtype specific reverse primer or a mutation specific reverse primer, was used to determine the ratio of mutated vs. wildtype alleles. The sensitivity of the PCR assay was determined by dilution series to be better than 1:10000. In the cell fractions we defined a minimum of 5 % mutated alleles to be significant. Results: All 13 patients had JAK2 V617F clonal granulocytes with a median proportion of mutated alleles of 60%, ranging from 8–96%. Eight patients (PV= 6, IMF=2) had more than 50 % mutated alleles in their granulocytes indicating homozygocity. Twelve (PV=10, IMF=2) out of 13 patients had clonal monocytes, median proportion of mutated alleles 35%, range (2–84%). Five patients had homozygote monocytes. Median proportion of mutated alleles in T-lymphocytes was 3%, range (0.24–83%), and four patients (PV=2, IMF=1, ET=1) had T-lymphocytes with more than 5% mutated alleles, 2 of them being homozygote. In B-lymphocytes only 2 patients had more than 5 % mutated alleles, none were homozygote. Median proportion of mutated alleles 3.5 %, range (1–46%). Conclusions: By a highly sensitive realtime quantitative PCR assay we have demonstrated that the JAK2 V617F mutation is an event in an early stem cell with the potential of both myeloid and lymphoid differentiation. The fraction of mutated alleles varies not only within the different cell types, but also to a great extend between individual patients. As expected all 13 patients harboured the mutation in their granulocytes Twelve, five and two patients had clonal JAK2 mutated monocytes, T-cells and B-cells respectively. The ratio of mutated vs. wt alleles allowed us to determine homozygocity in 8 cases within a specific cell type, mostly granulocytes, but homozygocity was also detected in monocytes and T-cells. In conclusion this highly sensitive quantitative assay may detect more JAK2 V617F patients than previously reported assays and may be useful in monitoring the size of the mutated clone during cytoreductive therapy.

Introduction: The JAK2V617F mutation is believed to occur in an early stem cell. Analysis of the JAK2mutational status of patients suspected of a chronic myeloproliferative disorder has already been widely introduced into the diagnostic procedure. The ability to determine the size of the mutated clone and to monitor its evolution over time would be of great interest. Most methods are based on sequencing and qualitative or semi-quantitative PCR methods with limited sensitivity We present a highly sensitive real-time quantitative PCR assay, and have determined the percentage of mutated alleles in granulocytes, monocytes, T-lymphocytes and B-lymphocytes.