Hematological Oncology最新文献

Adult T-cell leukemia-lymphoma (ATL) is a rare, aggressive malignancy prevalent in Japan, the Caribbean, and Central/South America. This multicenter retrospective study evaluated the effectiveness and safety of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisolone (BV-CHP) in patients aged ≥ 18 years with previously untreated CD30-positive ATL, verified through immunohistochemistry/flow cytometry, from six hospitals in Japan. Outcomes included overall response rate (ORR; primary outcome), overall survival (OS), progression-free survival (PFS), complete response rate (CRR), disease control rate (DCR), and safety. Subgroup analyses evaluated lesion site, ATL subtype, age, and CD30 expression. Of 46 screened patients, 36 (median age 71 years; 66.7% female) were analyzed and started BV-CHP between April 2020 and January 2024. CD30 positivity was confirmed in all patients. ORR was 86.1% (95% confidence interval [CI] 70.5–95.3), CRR 61.1% (95% CI 43.5–76.9), and DCR 91.7% (95% CI 77.5–98.3). ORR by lesion site (lymph nodes, peripheral blood, skin) was 93.8%, 90.9%, and 83.3%, respectively, by ATL subtype (acute, lymphoma) was 78.9% and 94.1%, respectively, and by age (≤ 70 years, > 70 years) was 84.6% and 87.0%, respectively. One patient with CD30 expression < 10% achieved a complete response; ORR was 73.7% in 19 patients with CD30 expression ≥ 10%. Median OS and PFS was 535 days (95% CI 343–not estimable) and 205 days (95% CI 166–279), respectively. Treatment-emergent adverse events of any grade and grade ≥ 3 both occurred in 88.9% of patients, with neutropenia, febrile neutropenia, and thrombocytopenia being most common. Among 11 patients who underwent allogeneic stem cell transplantation, two developed acute graft-versus-host disease; median PFS was 234 days (95% CI 168–343), compared with 180 days (95% CI 96–279) without transplantation. BV-CHP demonstrated high ORR and CRR across age groups and ATL subtypes with a manageable safety profile, supporting its potential use as a standard treatment option.

Clonal hematopoiesis of indeterminate potential (CHIP) is a predisposing condition to lymphoma development. CHIP carrying mutations that are recurrently found in lymphomas are designated as L-CHIP. We presume that bone marrow-derived L-CHIP populations are able to expand and manifest in peripheral lymphoid tissues, where they could hence be called L-CHIP tissue-equivalents. There, they may proliferate and foster unexplained follicular hyperplasias, and, thus, potentially represent an early precursor of lymphoma. Analogously, we hypothesize that certain germline-derived mutations lead to lymphoproliferations (germline-derived lymphoproliferations) in otherwise healthy individuals. We collected seven exceptional cases of symptomatic nodal and extranodal lymphoid hyperplasias, which were all morphologically suspicious and displayed somatic and/or germline-derived mutations recurrently found in B-cell lymphomas. One patient developed follicular lymphoma after 8 years carrying the same non-productive immunoglobulin rearrangement detected in the initial biopsy. L-CHIP tissue-equivalents and germline-derived lymphoproliferations potentially represent first steps in lymphomagenesis and knowledge about their existence might be of diagnostic utility in challenging cases of (atypical) lymphoproliferations. With histology, immunohistochemistry, and molecular testing, such lesions can be identified in situ.

Follicular lymphoma (FL) is an indolent disease characterized by multiple relapses and eventual refractoriness to therapy. Despite advancements in therapeutic approaches, FL treatment algorithm and management remain not well-established, necessitating both ongoing research into novel therapeutic strategies and in stating patient journey. We propose a comprehensive overview of current standard treatments for relapsed or refractory (R/R) FL, including chemoimmunotherapy and stem cell transplantation, and insights into emerging therapies such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies. We discuss the efficacy and safety profiles of these innovative treatments, their integration into the therapy armamentarium, and the potential they hold in altering the natural history of FL. Additionally, we propose a therapeutic flow depending on POD24 (i.e., progression of disease within 24 months), transformed disease, early relapse and fast/low progression, with the aim to provide a useful tool to all physicians dealing with this disease for achieving sustained remission and improving the quality of life in patients with R/R FL.

Over the past 2 decades, advancements in follicular lymphoma (FL) treatment, particularly with anti-CD20 antibodies, have significantly improved patient survival. However, a subset of FL patients experiences early relapse and progression within 24 months (POD24) after first line treatment, which is a sign of poor prognosis. Current guidelines recommend various second-line treatments, but there is no consensus on an optimal treatment sequence for relapsed/refractory (r/r) FL. Moreover, despite available treatments, reduced survival after second-line therapies and diminishing responses with each relapse highlight the unmet need for more effective options. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment for r/r FL beyond 2^nd line therapy, with three FDA/EMA-approved therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) showing high efficacy and manageable side effects. However, challenges remain in determining which patients will benefit most from CAR-T, especially given its high cost, safety concerns, and logistical barriers. A consensus study was conducted to guide CAR-T patient selection and treatment sequencing for patients in 3rd line or beyond. Key findings suggest that younger patients, those with high disease burden or poor first-line responses, should be prioritized for CAR-T. Additionally, CAR-T is recommended as a third-line option for patients with POD24, double refractoriness (failure to respond to two subsequent lines of immunochemotherapy), or early autologous stem cell transplant failure. The study underscores the importance of early assessment of treatment response, careful second-line therapy selection, and patient adherence to ensure optimal outcomes. The results, based on expert consensus, support CAR-T therapy as a viable option for r/r FL patients, offering hope for durable remissions in this challenging cohort.