-
EClinicalMedicine Jul 2023Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite...
BACKGROUND
Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite major treatment advances in the treatment of LNs over the last two decades, a comprehensive evaluation of tMDS/AML trends following both common and rare LNs treated in this contemporary period is lacking.
METHODS
In US cancer registries during 2000-2018, we identified 1496 tMDS/AML cases among 186,503 adults who were treated with initial chemo/immunotherapy for first primary LN and survived ≥1 year. We quantified tMDS/AML standardized incidence ratios (SIRs), excess absolute risks (EARs, per 10,000 person-years), and cumulative incidence.
FINDINGS
The highest tMDS/AML risks occurred after precursor leukemia/lymphoma (SIR = 39, EAR = 30), Burkitt leukemia/lymphoma (SIR = 20, EAR = 24), peripheral T-cell lymphoma (SIR = 12, EAR = 23), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; SIR = 9.0, EAR = 27), and mantle cell lymphoma (SIR = 8.5, EAR = 25). Elevated risks (SIRs = 4.2-6.9, EARs = 4.9-15) also were observed after all other LN subtypes except hairy cell leukemia and mycosis fungoides/Sézary syndrome. Among patients treated more recently, tMDS/AML risks were significantly higher after CLL/SLL (SIR = 4.8, SIR = 10, P = 0.0043), significantly lower after Hodgkin (SIR = 15, SIR = 6.3, P = 0.024) and marginal zone (SIR = 7.5, SIR = 2.3, P = 0.015) lymphomas, and non-significantly lower after mantle cell lymphoma (SIR = 10, SIR = 3.2, P = 0.054), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR = 6.9, SIR = 1.0, P = 0.067), and plasma cell neoplasms (SIR = 5.4, SIR = 3.1, P = 0.051). EAR and cumulative incidence trends generally were similar to SIR trends. Median survival after tMDS/AML was 8.0 months (interquartile range, 3.0-22.0).
INTERPRETATION
Although tMDS/AML risks are significantly elevated after initial chemo/immunotherapy for most LNs, patients treated more recently have lower tMDS/AML risks, except after CLL/SLL. Though rare, the poor prognosis following tMDS/AML emphasizes the importance of continued efforts to reduce treatment-associated toxicity.
FUNDING
This research was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. LMM, GMD, REC, and CBS verified the data, and all authors had access to the data and made the decision to submit for publication.
PubMed: 37457112
DOI: 10.1016/j.eclinm.2023.102060 -
The Oncologist Aug 2023Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular...
Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced -mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy.
Topics: Humans; Myocarditis; Retrospective Studies; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Myositis; Myasthenia Gravis
PubMed: 37285523
DOI: 10.1093/oncolo/oyad155 -
Blood Advances Aug 2023Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2...
Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2 study evaluated the efficacy and safety of the programmed cell death protein 1 inhibitor tislelizumab in these patients. Seventy-seven patients were treated with 200 mg tislelizumab every 3 weeks. Twenty-two patients with extranodal NK-/T-cell lymphomas were enrolled in cohort 1; 44 patients with peripheral T-cell lymphoma (PTCL) were enrolled in cohort 2 (21 patients had PTCL not otherwise specified, 11 patients had angioimmunoblastic T-cell lymphoma, and 12 patients had anaplastic large-cell lymphoma). Cohort 3 comprised 11 patients with cutaneous T-cell lymphoma, of which 8 patients had mycosis fungoides (MF) and 3 had Sézary syndrome. Of the 77 patients, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% received ≥3 prior systemic regimens. Promising efficacy was observed in cohort 3 (median follow-up [FU], 16.6 months; overall response rate [ORR], 45.5%; complete response [CR], 9.1%; median duration of response [DOR], 11.3 months; median progression-free survival, 16.8 months; median overall survival, not reached). Modest efficacy was observed in cohort 1 (median FU, 8.4 months; ORR, 31.8%; CR, 18.2%; median DOR, not reached) and cohort 2 (median FU, 9.3 months; ORR, 20.5%; CR, 9.1%; median DOR, 8.2 months). Most treatment-related adverse events were grade 1 or 2, and the safety profile was consistent with the known safety profile of tislelizumab. In conclusion, tislelizumab was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions. This trial was registered at www.clinicaltrials.gov as #NCT03493451.
Topics: Humans; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Killer Cells, Natural
PubMed: 37276067
DOI: 10.1182/bloodadvances.2022009575 -
The Journal of Investigative Dermatology Dec 2023
Topics: Humans; Programmed Cell Death 1 Receptor; Sezary Syndrome; Skin Neoplasms
PubMed: 37270066
DOI: 10.1016/j.jid.2023.03.1687 -
Seminars in Cell & Developmental Biology Feb 2024Mycosis Fungoides (MF) and Sézary Syndrome (SS) belong to a wide spectrum of T cell lymphoproliferative disorders collectively termed cutaneous T cell lymphomas (CTCL).... (Review)
Review
Mycosis Fungoides (MF) and Sézary Syndrome (SS) belong to a wide spectrum of T cell lymphoproliferative disorders collectively termed cutaneous T cell lymphomas (CTCL). CTCLs represent an archetype of heterogeneous and dynamically variable lymphoproliferative neoplasms typified by distinct clinical, histological, immunophenotypic, and genetic features. Owing to its complex dynamics, the pathogenesis of CTCL remains elusive. However, in recent years, progress in CTCL classification combined with next-generation sequencing analyses has broadened the genetic and epigenetic spectrum of clearly defined CTCL entities such as MF and SS. Several large-scale genome studies have identified the polygenic nature of CTCL and unveiled an idiosyncratic mutational landscape involving genetic aberrations, epigenetic alterations, cell cycle dysregulation, apoptosis, and the constitutive activation of T cell/NF-κB/JAK-STAT signaling pathways. In this review, we summarize the evolving insights on how the intrinsic epigenetic events driven by dysregulated miRNAs, including the oncogenic and tumor-suppressive miRNAs, influence the pathogenesis of MF and SS. We also focus on the interplay between the JAK/STAT pathway and miRNAs in CTCL as well as the significance of the miRNA/STAT axis as a relevant pathogenetic mechanism underlying CTCL initiation and progression. Based on these biologic insights, the current status and recent progress on novel therapies with a strong biological rationale, including miRNA-targeted molecules and JAK/STAT-targeted therapy for CTCL management, are discussed.
PubMed: 36216715
DOI: 10.1016/j.semcdb.2022.09.015