First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer.

Background: Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.

Methods: We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety.

Lymphoma patients treated with anti-CD20 and chemotherapy display disconnected T and B cell responses to COVID-19 vaccine.

Due to immunosuppressive treatment, COVID-19 vaccination is challenging in patients with B-cell lymphoma. We prospectively evaluated CD4, CD8 T-cell and serological responses to the COVID-19 mRNA vaccine in a cohort of patients treated for a B-cell lymphoma with anti-CD20 therapy. During lymphoma treatment, CD4, CD8, and CD19 cell dropped.

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.

Incidence and impact of other malignancies after immunochemotherapy by fludarabine, cyclophosphamide, and rituximab as frontline treatment for chronic lymphocytic leukemia: A single-center retrospective study.

Individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have a high risk of developing other malignancies (OMs). The development of OMs may be associated with the advanced age of CLL/SLL patients, presence of a tumor-promoting microenvironment, immune alterations inherent to CLL/SLL, or chemotherapy. Importantly, the occurrence of OMs following frontline fludarabine, cyclophosphamide and rituximab (FCR) treatment is associated with a reduction in the overall survival (OS).

Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines.

Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management.

Evaluation and management of hepatic dysfunction, portal hypertension and portal/splanchnic vein thrombosis in patients with myelofibrosis undergoing allogeneic haematopoietic cell transplantation: A practice based survey on behalf of the Chronic Malignancies Working Party of the EBMT.

Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded.

Haploidentical hematopoietic cell transplantation as a platform for natural killer cell immunotherapy.

An innovative approach is crucially needed to manage relapse after allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematological malignancies. This review explores key aspects of haploidentical HCT with post-transplant cyclophosphamide, highlighting the potential and suitability of this platform for natural killer (NK) cell immunotherapy. NK cells, known for their unique abilities to eliminate cancer cells, can also exhibit memory-like features and enhanced cytotoxicity when activated by cytokines.

Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation.

We evaluated the impact of early recovery of mucosal-associated invariant T cells (MAIT) and gamma-delta (γδ) T cells, especially Vδ2 T cells, on the clinical outcomes of 76 patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT). MAIT cells were identified at day 20-30 post-transplant using flow cytometry and defined as CD3 TCRVα7.2CD161.

Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor overall survival.

The use of CD34+ selected stem cell boost (SCB) after allogeneic hematopoietic cell transplant (allo-HCT) has been increasing. Predictors of treatment failure after SCB, both in the context of poor graft function (PGF) or other settings, are not well characterized. We report among the largest single-center retrospective experiences of the use of SCB and evaluate potential predictors of response and outcomes.

Transplantation for myelofibrosis patients in the ruxolitinib era: a registry study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

In this SFGM-TC registry study, we report the results after stem cell transplantation (HSCT) in 305 myelofibrosis patients, in order to determine potential risk factors associated with outcomes, especially regarding previous treatment with ruxolitinib. A total of 102 patients were transplanted from an HLA-matched-sibling donor (MSD), and 143 patients received ruxolitinib. In contrast with previous studies, our results showed significantly worse outcomes for ruxolitinib patients regarding overall survival (OS) and non-relapse mortality (NRM), especially in the context of unrelated donors (URD).

Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor.

Bi- and Tri-specific antibodies in non-Hodgkin lymphoma: current data and perspectives.

Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin's lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies.

Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft.

Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis.

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT.