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1.
Hematol Oncol ; 40(4): 763-776, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35368106

ABSTRACT

Second allogeneic stem cell transplantation (allo-SCT2) represents a rescue option for selected patients (pts) with relapsed/refractory (r/r) acute myeloid leukemia (AML). Still, relapse rates post-allo-SCT2 remain high and effective anti-relapse strategies and predictive biomarkers remain to be defined. We here analyzed a cohort of 41 AML patients (pts) undergoing allo-SCT2 in our center. Allo-SCT2 induced a third hematologic complete remission (CR) in 37 pts, at costs of a 36% non-relapse mortality rate. Furthermore, 19 pts eventually relapsed post allo-SCT2. Addressing relapse after allo-SCT2, 14 pts (74%) underwent cell-based anti-relapse strategies, including third allogeneic transplantation (allo-SCT3; 3/14), donor lymphocyte infusions (DLIs) combined with either 5-azacytidin and venetoclax (4/14) or chemotherapeutic agents (7/14). Notably, six of seven pts (86%) who received either allo-SCT3 or a combination therapy of DLIs, 5-azacytidine and venetoclax achieved CR despite poor cytogenetics post-allo-SCT2 (e.g., TP53). Finally, 11 of 41 pts were alive at the last follow-up (seven CR2, three CR3, one partial remission) resulting in estimated 2- and 5-year overall survival of 35% and 25%, respectively.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Azacitidine , Bridged Bicyclo Compounds, Heterocyclic , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Myeloid, Acute/therapy , Recurrence , Retrospective Studies , Sulfonamides
2.
Cancer Med ; 13(10): e7289, 2024 May.
Article in English | MEDLINE | ID: mdl-38770551

ABSTRACT

BACKGROUND: Mantle cell lymphoma (MCL) is a type of B-cell lymphoma that is currently incurable. Pirtobrutinib shows promising response rates in heavily pretreated MCL patients according to the approval study, but the real-world data are scarce. METHODS: In this study, we retrospectively analyzed the efficacy and safety profile of pirtobrutinib in 10 relapsed/refractory MCL patients from compassionate use program (CUP). RESULTS: On average, the patients underwent three lines of systemic therapy prior to pirtobrutinib and were predominantly BTKi exposed (9/10). The best overall response rate (BORR) was 67%. In a median follow-up of 8.6 months, the mean duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were not reached. No new safety signals were documented. CONCLUSIONS: In summary, pirtobrutinib represented a safe and effective treatment option in a small real-world population.


Subject(s)
Compassionate Use Trials , Lymphoma, Mantle-Cell , Humans , Lymphoma, Mantle-Cell/drug therapy , Male , Female , Aged , Middle Aged , Retrospective Studies , Europe , Treatment Outcome , Neoplasm Recurrence, Local/drug therapy , Aged, 80 and over , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Progression-Free Survival , Adult , Drug Resistance, Neoplasm
3.
Hemasphere ; 8(3): e54, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38510993

ABSTRACT

CD19-directed chimeric antigen receptor (CAR)-T cell therapy has become a standard treatment for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). While the benefits of CAR-T cell treatment are clear in the general patient population, there remains a relative scarcity of real-world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR-T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR-T infusion (<70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged <70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow-up of 8.3 months, median progression-free survival was 10.2 months (95% confidence interval [CI]: 6.5-21.8) and 11.1 months (95% CI: 4.9-NR) (p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8-NR) and 34.4 months (95% CI: 10.1-NR) (p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome (p = 0.53) or grade ≥3 neurotoxicity (p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR-T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR-T cell therapy should be not withheld for elderly patients with r/r DLBCL.

4.
Mol Oncol ; 14(3): 571-589, 2020 03.
Article in English | MEDLINE | ID: mdl-31825135

ABSTRACT

Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma-promoting, alternatively activated M2-like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor-associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)-conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B-cell lymphoma (DLBCL) cells or, classically, by macrophage colony-stimulating factor (M-CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD-L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M-CSF stimulation in M2-like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose-dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL-TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co-cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma-only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206-positive cells, with high MRC1 expression being characteristic of HL-stage IV. In summary, the lymphoma-TAM interaction contributes to matrix-remodeling and lymphoma cell dissemination.


Subject(s)
Culture Media, Conditioned/pharmacology , Hodgkin Disease/metabolism , Lymphoma, B-Cell/metabolism , Macrophages/metabolism , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Tumor Microenvironment , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , B7-H1 Antigen/metabolism , CD40 Antigens/metabolism , Cell Differentiation/drug effects , Cell Line, Tumor , Chick Embryo , Chorioallantoic Membrane/metabolism , Chorioallantoic Membrane/pathology , Collagen Type I/metabolism , Culture Media, Conditioned/metabolism , Fluorescent Antibody Technique , Hodgkin Disease/immunology , Hodgkin Disease/pathology , Humans , Interleukin-13/metabolism , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/pathology , Macrophages/drug effects , Membrane Glycoproteins/immunology , Monocytes/metabolism , Neoplasm Metastasis/immunology , Proteome/genetics , Proteome/metabolism , RNA-Seq , Receptors, Cell Surface/metabolism , Receptors, Immunologic/immunology , Up-Regulation , Xenograft Model Antitumor Assays
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