Management of Adverse Reactions to Loncastuximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma in the world. Treatment options for relapsed DLBCL in the third line and beyond include chimeric antigen receptor T-cell therapy, T-cell-engaging bispecific antibodies, and loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), each with unique toxicity profiles. There is still an unmet need for guidance on managing Lonca-associated adverse events (AEs), particularly for oncologists who have limited experience with this antibody-drug conjugate.

New Comorbidity Index Associated with Survival After Chimeric Antigen Receptor T Cell Therapy for Large B-Cell Lymphoma.

The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T cell (CAR-T) therapy is not well-established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017-2020 were selected from the CIBMTR registry.

NKTR-255 Enhances Complete Response Following CD19 CAR-T in Patients with Relapsed/Refractory Large B-cell Lymphoma.

Autologous T-cells engineered to express CD19-directed chimeric antigen receptor (CAR) have shown high overall response rates in treatment-refractory large B-cell lymphoma (LBCL). However, more than half of patients do not attain a durable response and will eventually relapse. Thus, strategies to improve long-term efficacy of CAR T-cell products are needed.

A Phase I Trial of Evorpacept, Lenalidomide and Rituximab for Patients with B-cell Non-Hodgkin Lymphoma.

Introduction: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab (R2) in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages.

Methods: Adult patients with B-NHL who had received at least 2 prior lines of systemic therapy were included in this single arm phase I study (NCT05025800).

Real-world outcomes of brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma: a CIBMTR analysis.

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T-cell therapy approved for relapsed/refractory mantle cell lymphoma (r/r MCL). Here, we report real-world effectiveness and safety outcomes of brexu-cel in a prospective study of patients with r/r MCL, including subgroups based on prior treatment with Bruton's tyrosine kinase inhibitor, bendamustine, or autologous hematopoietic cell transplant (auto-HCT) and number of prior therapy lines, using Center for International Blood and Marrow Transplant Research registry data. A total of 476 patients with r/r MCL who received brexu-cel between July 2020 and December 2022 were included in the analysis.

Outcomes of allogeneic HCT in Hodgkin lymphoma in the era of checkpoint inhibitors: a joint CIBMTR and EBMT analysis.

Checkpoint inhibitors (CPIs) have shown remarkable efficacy in Hodgkin lymphoma (HL), and are now used routinely. While allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for HL, there are concerns prior CPIs may exacerbate post-allo-HCT complications, particularly graft-versus-host disease (GVHD), and lead to worse outcomes. Given the relative paucity of data, we performed a Center for International Blood and Marrow Transplant Research/European Society for Blood and Marrow Transplantation study to examine the impact of prior CPIs in allo-HCT.

Risk Factors for Solid Organ Graft Failure and Death in Hematopoietic Cell Transplant Recipients Undergoing Solid Organ Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research and Organ Procurement and Transplantation Network Study.

Background: There is a growing population of hematopoietic cell transplantation (HCT) survivors who later require a solid organ transplant (SOT). However, there are limited data on survival, risk factors (RFs) for SOT graft loss, and death.

Methods: This is a retrospective Center for International Blood and Marrow Transplant Research study that included recipients of HCT followed by SOT between 2001 and 2017.

Risk Factors for Solid Organ Graft Failure and Death in Solid Organ Transplant Recipients Undergoing Hematopoietic Cell Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research (CIBMTR) and Organ Procurement and Transplantation Network (OPTN) Study.

Background: There is a growing population of solid organ transplant (SOT) survivors who subsequently require a hematopoietic cell transplant (HCT), although there are limited data on survival, risk factors for SOT graft loss, and death in this cohort.

Methods: This retrospective Center for International Blood and Marrow Transplant Research study included recipients of SOT followed by HCT between 1989 and 2017. HCT data were merged with organ transplant data from the Organ Procurement and Transplantation Network.

Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826.

Older patients with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients. We report a subset analysis of older patients (60 years and older) enrolled in the phase three S1826 trial conducted by SWOG that randomly assigned patients with newly diagnosed advanced-stage (III-IV) cHL to six cycles of nivolumab (N)-AVD or brentuximab vedotin (BV)-AVD. Of 103 enrolled patients 60 years and older, 99 were eligible.

A phase 2 study of obinutuzumab combined with lenalidomide in previously untreated high tumor burden follicular lymphoma.

Follicular lymphoma (FL) has a clinical course that is often characterized by high response rates to first-line therapy, followed by multiple relapses over a prolonged natural history. Currently, there are multiple possible approaches to frontline therapy for untreated advanced-stage FL, but there is an ongoing debate around what is the preferred approach. Based on the benefits seen with combining lenalidomide, an immunomodulatory agent, with rituximab, an anti-CD20 antibody, we aimed to evaluate the safety and efficacy of lenalidomide in combination with obinuzutumab, an anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity.

Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma.

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized relapsed/refractory lymphoma treatment but can cause severe immune-related adverse events (irAEs), including pneumonitis. The incidence and risk factors for ICI-pneumonitis in real-world lymphoma cohorts remain unreported.

Methods: We retrospectively reviewed 302 lymphoma patients treated with PD-1 inhibitors at MD Anderson (2015-2022).

Trends in Radiation Use from 2004 to 2020 among Adolescents and Young Adults with Hodgkin Lymphoma.

Background: Hodgkin lymphoma has excellent survival rates in adolescents and young adults (AYA, diagnosed between ages 15 and 39 years). However, survivors are at risk of treatment-related late effects. Whereas radiotherapy (RT) de-escalation/omission has emerged as an approach to minimize late effects, no prior studies have evaluated RT use over time in AYAs with Hodgkin lymphoma.

Differences in time to treatment and impact on overall survival in adolescents and young adults with Hodgkin lymphoma.

Delays in time to treatment (TTT) have been shown to affect cancer survival, yet this has not been investigated in adolescent and young adult (AYA) Hodgkin lymphoma (HL) patients. This retrospective analysis included 508 patients with TTT defined as the time between diagnosis and chemotherapy start. The median TTT for the population was 28 days (IQR: 12-44).

Cytokine Release Syndrome and Neurotoxicity Following CD19 CAR-T in B-Cell Lymphoma.

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity.

How we treat mantle cell lymphoma with cellular therapy in 2025: the European and American perspectives.

Cellular therapies have been cornerstones of the treatment of mantle cell lymphoma (MCL) for decades and have helped to improve the outcome of this formerly very unfavourable B-cell lymphoma considerably. Current established roles of cellular therapies include autologous hematopoietic cell transplantation (HCT) as part of first-line therapy, chimeric antigen receptor-engineered T-cells (CART) for relapsed/refractory MCL, and allogeneic HCT for settings in which CARTs have failed or are unavailable. Therapeutic innovations have recently entered the MCL treatment landscape and are moving upstream in treatment algorithms, challenging the existing management principles.

Cytokine Storms in COVID-19, Hemophagocytic Lymphohistiocytosis, and CAR-T Therapy.

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial.

Outcomes of patients with CD30-positive (CD30) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, anti-PD1 checkpoint inhibitors (CPI). However, there is a need for new therapies for patients with tumors refractory to both BV and CPI, who face dismal outcomes. AFM13-a CD30/CD16A bispecific antibody-activates natural killer (NK) cells to kill CD30 cells.

Outcomes and Risk Factors for Influenza and Respiratory Syncytial Virus Lower Respiratory Tract Infections and Mortality in Patients With Lymphoma or Multiple Myeloma: A 7-Year Retrospective Cohort Study.

Background: Respiratory viral infection (RVI) is a significant complication in patients with hematologic malignancies. While risk factors of lower respiratory tract infections (LRIs) and mortality have been studied in allogeneic hematopoietic cell transplant recipients, data remain limited for patients with lymphoma and multiple myeloma (MM). We investigated outcomes and risk factors of LRI and mortality secondary to respiratory syncytial virus (RSV) or influenza virus (IFV) infections in these populations.

Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.

Background: Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.

Objective: Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma.

Outcomes with bridging radiation therapy prior to chimeric antigen receptor T-cell therapy in patients with aggressive large B-cell lymphomas.

Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.

Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023.

Direct-Acting Antivirals Induce Lymphoproliferative Disease Response in HCV-Infected Patients With Indolent B-Cell Non-Hodgkin's Lymphoma: A Prospective Observational Study.

B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients.

Phase 2 trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas.

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma.

Impact of vein-to-vein time in patients with R/R LBCL treated with axicabtagene ciloleucel.

Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.

Enhancement of High-Dose Chemotherapy and Autologous SCT with the PARP Inhibitor Olaparib for Refractory Lymphoma.

Purpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a PARP inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by the inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.