PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial.

Purpose: Significant progress has occurred in developing quantitative PET/CT biomarkers in diffuse large B-cell lymphoma (DLBCL). Total metabolic tumor volume (MTV) is the most extensively studied, enabling assessment of FDG-avid tumor burden associated with outcomes. However, prior studies evaluated the outcome of cytotoxic chemotherapy or chimeric antigen receptor T-cell therapy without data on recently approved FDA agents.

Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase II LOTIS-2 study.

Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment.

Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL.

Copy Number Loss at Chromosome 14q11.2 Correlates With the Proportion of T Cells in Biopsies and Helps Identify T-Cell Neoplasms.

Context.—: Evidence of T-cell clonality is often critical in supporting the diagnosis of a T-cell lymphoma.

Objectives.

Association of a Dominant T-Cell Clone in Peripheral Blood With Time to Systemic Treatment in Patients With Stage IB Mycosis Fungoides.

This cohort study of data from 39 patients assesses whether the presence of a dominant T-cell receptor clone in peripheral blood is associated with time to systemic treatment in patients with stage IB mycosis fungoides.

T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy.

Introduction: Chimeric antigen receptor T (CAR-T) cells targeting CD19 result in durable responses in approximately 40% of DLBCL patients. Loncastuximab tesirine, an antibody drug conjugate targeting CD19 with a pyrrolobenzodiazepine payload, has activity against DLBCL.

Patients And Methods: We evaluated the outcomes of 13 DLBCL patients relapsed after CAR-T cells treated with loncastuximab in the LOTIS-2 trial.

Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma.

We developed an integrated population pharmacokinetic model to investigate loncastuximab tesirine pharmacokinetics (PK) and exposure-response relationships for relapsed/refractory B cell non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL). The model, based on the recommended dosing schedule (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter) and drug concentrations in phase 1 and 2 studies (DLBCL [n = 284], non-DLBCL [n = 44]), was used to characterize loncastuximab tesirine PK and evaluate exposure covariates. Relationships between exposure (pyrrolobenzodiazepine-conjugated antibody [cAb] cycle 1 average concentration) and (1) efficacy (including overall response rate [ORR; primary endpoint] and overall survival [OS]) and (2) grade ≥ 2 treatment-emergent adverse events were explored.

Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models.

CD70 is a member of the tumor necrosis factor receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T-cell lymphomas and conducted preclinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate (ADC), using patient-derived xenograft cutaneous T-cell lymphoma (CTCL PDX) models.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473).

Current and emerging treatment options in primary mediastinal B-cell lymphoma.

Previously considered a subtype of diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) is now recognized by the World Health Organization as an independent entity. PMBCL has clinicopathologic features that are separate from systemic DLBCL and harbors some biologic characteristics which overlap with nodular sclerosing classic Hodgkin's lymphoma (cHL). Similar to cHL, copy number alterations of 9p24.

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.

Background: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL.

High incidence of fractures after R-CHOP-like chemotherapy for aggressive B-cell non-Hodgkin lymphomas.

Purpose: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL.

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial.

Introduction: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination.

Association of a Proposed New Staging System for Folliculotropic Mycosis Fungoides With Prognostic Variables in a US Cohort.

Importance: A new cutaneous staging system for folliculotropic mycosis fungoides (FMF) has been purported to better estimate survival compared with the staging system for conventional mycosis fungoides.

Objective: To analyze predictive variables associated with survival and evaluate the effectiveness of the newly proposed staging system for estimating overall survival and disease-specific survival (DSS) in a US cohort.

Design, Setting, And Participants: This cohort study assessed 195 patients with FMF in the dermatopathology database of the University of California, San Francisco from January 1, 1990, to April 31, 2012, for eligibility.

Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation.

Background: More than one-half of high-risk patients with relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) relapse after autologous hematopoietic cell transplantation (auto-HCT). In this phase II study, we investigate the long-term outcomes of high-risk patients with rrDLBCL receiving intensive consolidation therapy (ICT) with OVA (ofatumumab, etoposide, and high-dose cytarabine) prior to auto-HCT.

Patients And Methods: The primary endpoints were the ability of OVA to mobilize peripheral stem cells and the 2-year progression-free survival (PFS) rate following OVA.

NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens.

Serial comprehensive geriatric and quality of life assessments in adults age ≥ 50 years undergoing autologous hematopoietic cell transplantation.

Objectives: We sought to examine the natural history of geriatric assessment (GA) and quality of life (QOL) domains among adults age ≥ 50 years undergoing autologous hematopoietic cell transplantation (autoHCT).

Materials And Methods: A QOL tool and cancer-specific GA were completed before autoHCT in patients ≥50 years, and at 100 days, six months, and one year post-transplant.

Results: One hundred eighty-four patients completed the pre-transplant QOL/GA assessment, 169 (92%) completed the 100-day assessment, 162 (88%) completed the six-month assessment, and 145 (79%) completed the twelve-month assessment.