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.

Inhibiting KRAS with CD47 and immune checkpoint overcomes intrinsic resistance to combined KRAS and immune checkpoint inhibitor therapy.

Although Kirsten rat sarcoma virus (KRAS) G12C inhibitors alter the treatment strategy for patients with KRAS G12C-mutant lung cancer, their efficacy remains insufficient to eliminate tumors. Here, we identify that inhibition of mutant KRAS promotes escape from macrophage phagocytosis by upregulating the expression of cluster of differentiation 47 (CD47) and CD24. These proteins are induced by the binding of FOXA1 to the super-enhancer of CD47 and grainyhead-like transcription factor 2 (GRHL2) to the promoter of CD24, respectively.

JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors.

Background: While chimeric antigen receptor (CAR)-T cell therapy exhibits a robust therapeutic efficacy against B-cell malignancies and multiple myeloma, its efficacy and safety have not been established for acute myeloid leukemia (AML) and solid tumors due to the paucity of established target antigens. Some AML and solid tumor cells express tumor necrosis factor (TNF), which is initially expressed on the cell surface prior to shedding.

Methods: In this study, we obtained monoclonal antibodies against the N-terminal fragment of TNF (TNF-NTF) that remains on the cell surface after shedding.

Prognostic impact of RDI of vincristine in patients with DLBCL receiving R-CHOP: a supplementary analysis of JCOG0601.

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [VCR], and prednisolone) is the standard of care for previously untreated patients with diffuse large B-cell lymphoma (DLBCL). However, some DLBCL survivors experience long-lasting VCR-related peripheral neuropathy (PN). VCR dose is usually reduced based on PN severity, but inconsistent results have been reported regarding the effect of VCR dose reduction on the prognosis of patients with DLBCL.

Immunosuppressive Effects of Multiple Myeloma-Derived Extracellular Vesicles Through T Cell Exhaustion.

Extracellular vehicles (EVs) are reported to be involved in several processes relating to tumor progression, including angiogenesis, osteolysis, and drug resistance in multiple myeloma (MM). However, the role of EVs in the immune-suppressive milieu of MM is poorly understood. Here, we investigated the effects of MM-derived EVs on T cells, focusing on markers of T cell exhaustion.

Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed/refractory MM.

The bispecific antibody talquetamab demonstrated substantial responses in heavily pretreated relapsed or refractory multiple myeloma (RRMM) in the global phase 1/2 MonumenTAL-1 study. This study, evaluated the safety and efficacy of talquetamab in Japanese patients with RRMM pretreated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. The primary endpoints were frequency and type of treatment-emergent adverse events (TEAEs) and serious AEs including dose-limiting toxicity (DLT).

Prevalence of CCR7-Positive CD8 T Cells as a Prognostic Factor in B-Cell Maturation Antigen -Targeted Chimeric Antigen Receptor T Cell Therapy.

Background: Chimeric antigen receptor T (CAR-T) cell therapy is effective for relapsed or refractory multiple myeloma (RRMM); however, relapse after the B-cell maturation antigen (BCMA) CAR-T cell therapy is associated with poor outcome. Hence, appropriate biomarkers that can predict the outcome are needed.

Methods: Patients who received idecabtagene vicleucel, a BCMA-targeted CAR-T cell therapy, were divided into two groups according to a cut-off value of 180 days for the progression-free survival (PFS) event.

Impact of MYD88 and/or CD79B mutations on central nervous system relapse in patients with diffuse large B-cell lymphoma.

This study examined the effect of myeloid differentiation primary response gene 88 mutation L265P (MYD88) and/or cluster of differentiation 79B gene mutation Y196 (CD79B) (MYD88/CD79B) on central nervous system (CNS) relapse in 270 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Over a median follow-up of 6.65 years, 20 patients experienced CNS relapse.

Efficacy and safety of isatuximab monotherapy to treat relapsed or refractory multiple myeloma: a pooled analysis of clinical trials.

This pooled analysis of phase 1 and 2 clinical trials evaluated the efficacy and safety of isatuximab as monotherapy in individuals with relapsed or refractory multiple myeloma (RRMM) who had previously received a median of 4.0 lines of therapy; safety data for individuals on isatuximab plus dexamethasone has also been evaluated. The efficacy analysis (n = 167) showed that isatuximab 20 mg/kg monotherapy was effective in the treatment of individuals with RRMM, with an overall response rate (ORR) of 26.

Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors.

Background: Effector regulatory T cells expressing C-C chemokine receptor 4 (CCR4) suppress antitumor immune responses. We conducted a phase I clinical trial to evaluate the safety and efficacy of preoperative combination therapy with mogamulizumab (an anti-CCR4 antibody) and nivolumab (an anti-programmed death-1 antibody) in patients with solid tumors.

Methods: Patients with operable solid tumors were enrolled in a 3+3 design, with preoperative nivolumab (3.

Clinical outcomes associated with anti-CD38-based retreatment in relapsed/refractory multiple myeloma: a systematic literature review.

Introduction: Anti-CD38-based therapy has become a backbone regimen for the treatment of multiple myeloma (MM), approved in first-, second-, and third-line settings. The effectiveness of anti-CD38-based retreatment after an initial relapse on previous anti-CD38-based therapy is unclear. Here we present the results of a systematic literature review investigating the clinical outcomes of anti-CD38-based retreatment in patients with relapsed/refractory MM.

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.

Characteristics and treatment patterns in patients with multiple myeloma in Japan: A retrospective cohort analysis.

Background: Approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies (mAbs), such as daratumumab, has reshaped treatment patterns in patients with multiple myeloma (MM) in Japan. This retrospective study evaluated patient characteristics, treatment patterns, and trends in MM patients using Medical Data Vision, the largest electronic health records database in Japan with anonymous inpatient and outpatient health information.

Methods: Patients aged ≥18 years, with ≥2 records of an MM diagnostic and disease code and ≥1 record of MM treatment between 01 April 2008 and 30 June 2023 were included.

Isatuximab plus pomalidomide and dexamethasone in frail individuals with relapsed/refractory multiple myeloma in Japan.

This post-marketing surveillance (PMS) assessed the safety and effectiveness of isatuximab plus pomalidomide and dexamethasone (Isa-Pd) for relapsed or refractory multiple myeloma (RRMM) in frail individuals during real-world use in Japan. Data from all individuals with RRMM treated with Isa-Pd in Japan between October 2020 and October 2021 were collected, with follow-up continued up to 12 months after starting Isa-Pd or until discontinuation. In the overall PMS population, 40 participants were classified as frail (33.

DREAMM-11, Part 2: Japanese phase I trial of belantamab mafodotin combination therapies in relapsed/refractory multiple myeloma.

DREAMM-11 (NCT03828292) was a Phase 1, open-label, dose-escalation study of belantamab mafodotin in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In Part 1, belantamab mafodotin monotherapy (2.5 or 3.

A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2.

Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma.

Here, we investigated the clinical significance of NOTCH1 and FBXW7 alterations for adult T-cell leukemia/lymphoma (ATLL) treatment outcomes. NOTCH1 alterations were identified in 37 (14.4%) of 257 patients, of which 33 were single nucleotide variants/insertion-deletions in the PEST domain, and 7 were in the heterodimerization or LIN-12/Notch repeats domains.

COVID-19 in patients receiving treatment at an outpatient chemotherapy unit.

During the COVID-19 pandemic period, many patients who required outpatient chemotherapy developed COVID-19, requiring chemotherapy interruption. However, there are no clear guidelines regarding the safe timing for restarting chemotherapy. We conducted a retrospective study to assess when such patients can safely recommence chemotherapy.

Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses.

Outcomes are poor in triple-class-exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.