Long-term outcomes of venetoclax and ibrutinib in Japanese patients with relapsed/refractory mantle cell lymphoma.

Background: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) face a poor prognosis in the absence of effective treatment options. Ibrutinib plus venetoclax demonstrated high response rates and a tolerable safety profile in the primary analysis of the Phase 2, M20-075 study (NCT04477486) in Japanese patients with R/R MCL. We report updated efficacy and safety from this study with longer follow-up.

Final results of JCOG0601 randomized trial of R-CHOP versus CHOP combined with dose-dense rituximab for diffuse large B-cell lymphoma.

Background: Despite several attempts to improve the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen remains the standard of care in previously untreated DLBCL. A randomized phase II/III study (JCOG0601) was performed to investigate the efficacy of dose-dense weekly rituximab combined with standard CHOP (RW-CHOP). Herein, we report the final results of JCOG0601 as a post hoc assessment after an 8-year follow-up.

Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial.

An unmet need exists for patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose disease remains incurable. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, is approved for R/R FL and different types of R/R large B-cell lymphoma after ≥2 prior lines of therapy (pLOT) in the US, Europe, and Japan. Regional data are critical to contextualize global trial data.

Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia.

Introduction: Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy.

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial.

Background: Primary results from the EPCORE NHL-3 trial (NCT04542824) showed deep, durable responses in Japanese patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with single-agent epcoritamab, a subcutaneous CD3xCD20 bispecific antibody. Here, we report 3-year follow-up of safety and efficacy.

Methods: Japanese patients with R/R CD20 DLBCL and  ≥ 2 prior systemic therapies received epcoritamab (0.

PI3Kδ Inhibitor Parsaclisib in Japanese Patients With Relapsed or Refractory Follicular Lymphoma.

Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in Japan, the United States, and Western Europe. Parsaclisib is a potent, selective next-generation PI3Kδ inhibitor that has demonstrated clinical efficacy and tolerability in phase II studies of patients with relapsed or refractory (R/R) B-cell NHL, including FL. We report results from CITADEL-213 (NCT04434937), a phase II study evaluating the efficacy and safety of parsaclisib in Japanese patients with R/R FL.

High FCGR2B Expression Can Identify Low-tumor-burden Follicular Lymphoma Patients Who Do Not Require Any Antilymphoma Therapy for a Long Term.

Spontaneous regression or a long-term lack of obvious progression is often observed in patients with low-tumor-burden (LTB) follicular lymphoma (FL). However, conventional prognostic risk models are unable to precisely identify the patients who will not require any antilymphoma treatment for a long term, especially at diagnosis. In this study, we identified genes whose expression levels were associated with the clinical outcome of LTB FL and verified their prognostic value using immunohistochemistry.

Obinutuzumab maintenance versus observation for patients with newly diagnosed high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy: a multicenter, randomized, phase III study (JCOG2008, MAIN study).

Maintenance therapy with monoclonal anti-CD20 antibody is the standard approach in patients with follicular lymphoma who initially treated and achieved response to immunochemotherapy. Maintenance therapy reduces the risk of lymphoma progression, but the risk of late or delayed fatal treatment-emergent adverse events is a clinically important issue. The aim of this randomized phase III study is to confirm the non-inferiority of observation compared to obinutuzumab maintenance therapy in patients with untreated high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy (JCOG2008, MAIN study).

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial.

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).

Improved prognosis of advanced-stage extranodal NK/T-cell lymphoma: results of the NKEA-Next study.

A retrospective study of extranodal natural killer/T-cell lymphoma (ENKL) patients diagnosed between 2014 and 2021 in Japan was conducted. Among 351 patients with sufficient data, 116 (33%) were in the advanced stage (5 in stage III and 111 in stage IV) at diagnosis, and were further analyzed. The median age was 60 years (range: 19-90), and 68 (59%) were male.

Treatments and Outcomes of Newly Diagnosed CD5-Positive Diffuse Large B-Cell Lymphoma: A Multi-Institutional Observational Study.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis and frequent central nervous system (CNS) relapse. Sandwich therapy comprising dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy and manageable safety in a phase II study of patients diagnosed with stage II-IV CD5+ DLBCL. To validate the results of that study and elucidate the current state of treatment for CD5+ DLBCL, we retrospectively analyzed the outcomes of patients with CD5+ DLBCL diagnosed between 2016 and 2021 who received anthracycline-containing chemotherapy with rituximab.

Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: an exploratory biomarker study of JCOG1105 (JCOG1105A1).

Purpose: A comprehensive analysis of metabolites (metabolomics) has been proposed as a new strategy for analyzing liquid biopsies and has been applied to identify biomarkers predicting clinical responses or adverse events associated with specific treatments. Here, we aimed to identify metabolites associated with bortezomib (Btz)-related toxicities and response to treatment in newly diagnosed multiple myeloma (MM).

Methods: Fifty-four plasma samples from transplant-ineligible MM patients enrolled in a randomized phase II study comparing two less-intensive regimens of melphalan, prednisolone and Btz (MPB) were subjected to the lipidomic profiling analysis.

A phase II study of zandelisib in patients with relapsed or refractory indolent non-Hodgkin lymphoma: ME-401-K02 study.

Zandelisib, a selective, potent PI3Kδ inhibitor, demonstrated favourable outcomes in patients with relapsed or refractory follicular lymphoma in a global phase II study. This phase II study evaluated the efficacy and safety of zandelisib for relapsed or refractory follicular lymphoma or marginal zone lymphoma. Sixty-one patients received zandelisib orally at 60 mg daily continuously in the first two 28-day cycles, followed by intermittent dosing on Days 1-7 following each cycle until progressive disease or unacceptable toxicity.

Long-term remission following CAR-T therapy in a patient with transformed follicular lymphoma relapse after allogeneic stem cell transplantation.

Follicular lymphoma (FL) may undergo histological transformation (HT) into a more aggressive lymphoma. Although rituximab for B-cell non-Hodgkin lymphomas (B-NHL) has greatly improved the overall survival (OS) of patients with transformed FL (tFL), relapse after anthracycline-based chemoimmunotherapy has a poor prognosis. CD19-targeting chimeric antigen receptor-modified T-cell (CAR-T) therapy is a promising treatment for relapsed or refractory (r/r) large B-cell lymphoma (LBCL), including tFL.

Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration.

Although rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly.

Successful Allogeneic Hematopoietic Stem Cell Transplantation for Nodal Epstein-Barr Virus-positive T/NK-cell Lymphoma.

Nodal Epstein-Barr virus-positive T/NK-cell lymphoma (EB-nTNKL) is an extremely rare disease characterized by an aggressive clinical course and poor prognosis, for which treatment strategies have not yet been established. We herein report a young man with EB-nTNKL. Although initial chemotherapies, including L-asparaginase, failed to produce a good response, subsequent myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT) resulted in favorable disease control and a long-term disease-free survival.

Successful Cord Blood Transplantation for Myeloid/Natural Killer Precursor Acute Leukemia: A Case Report and Literature Review.

A 21-year-old man was diagnosed with myeloid/natural killer precursor leukemia (MNKPL) with bone marrow infiltration of blasts of cyCD3, CD7, CD33, CD34, CD56, HLA-DR, cyMPO, and TdT immunophenotypes. Although hyper-hyperfractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone therapy was unsuccessful, induction treatment with idarubicin and cytarabine resulted in complete remission (CR). The patient subsequently underwent cord blood transplantation with a myeloablative conditioning regimen, which resulted in durable CR and complete donor chimerism.

Real-world retrospective analysis of immune checkpoint inhibitor therapy for relapsed or refractory Hodgkin's lymphoma.

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT).

Alemtuzumab monotherapy for T-cell prolymphocytic leukemia: an observational study in Japan.

Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78).

Plasma Venetoclax Concentrations in Patients with Acute Myeloid Leukemia Treated with CYP3A4 Inhibitors.

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol.