Hematological Oncology最新文献

The aim of this study was to describe the initial 3-year experience in vein-to-vein time for axi-cel therapy and the role of pharmacists in the first recruiting French centers. Retrospective observational data were collected for vein-to-vein time for commercial axi-cel after ≥ 2 lines of systemic therapy between January 2019 and December 2021 in the first 12 authorized French centers. Hospital pharmacists used a circuit database to ensure the prospective traceability at all steps. Totally 501 of the 562 intention-to-treat registrations on the database for cytapheresis (89,1%) led to the infusion of axi-cel. Median vein-to-vein time was shortened by 4 days. This was mainly due to tightening the interval from apheresis to release. The 36-day median vein-to-vein time achieved after 3 years' experience should be compared to the 29–34 days reported in Canada, the USA and Israel, where manufacturing sites are geographically closer to hospital centers than they are in France. The top 5 recruiting centers had the shortest vein-to-vein times. This French experience may serve as a model for other European centers, notably as regards deployment of pharmacists to improve the patient pathway with CAR T-cells and other gene and cellular therapies.

Patients with Hodgkin lymphoma (HL) or peripheral T-cell lymphoma (PTCL) who relapse after high-dose chemotherapy (HDCT) have a dismal prognosis. Brentuximab-vedotin (BV) is a CD30-targeting antibody-drug-conjugate (ADC) used in first-line-, salvage-, and maintenance-therapy of HL, as well as first-line- and salvage-therapy of PTCL. In phase I of this trial, we could show that BV can safely be added to BeEAM-HDCT (bendamustine, etoposide, cytarabine and melphalan). Here, we report the randomized phase II part of the trial comparing BV-BeEAM to BeEAM alone (ClinicalTrials.gov: NCT03187210). Primary endpoint was 1-year disease-free survival. Inclusion of 42 patients was planned but the study was terminated early, after a futility analysis showed lack of benefit. Twenty-five patients (HL: 11, PTCL: 14) who were planned to undergo HDCT were included. Median age was 60 years. Patients had a median of two prior therapies, and 11 were previously exposed to BV. Patients in the standard-arm had higher disease stage and (PTCL only) higher IPI. Duration of hospitalization, recovery of neutrophils/platelets, and infections were not significantly different between arms. No treatment related death occurred. However, two patients in the BV-arm developed grade 3 pneumonitis. After 22 months median follow-up, overall response-rate, complete remission-rate, disease-free survival and overall survival did not differ between groups. Pre-planned subgroup-analyses (HL-only, PTCL-only, only those achieving CR) did not show benefit in any subgroup. In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.

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.