FLT3 inhibitor maintenance after allogeneic stem cell transplantation in -mutated acute myeloid leukemia (AML) patients.

Background: The somatic mutation of fms-like tyrosine kinase 3 () in acute myeloid leukemia (AML) is associated with increased risk of relapse and lower survival rates. FLT3i as maintenance after allogeneic hematopoietic stem cell transplant (allo-HSCT) are under study to prevent disease relapse, but real-world data are lacking.

Methods: We performed a single center, retrospective cohort study and analyzed patients who had -mutated AML and underwent allogeneic-HSCT between January 2011 to June 2022 at the University of Chicago.

Optimization of Metabolic Tumor Volume as a Prognostic Marker in CAR T-Cell Therapy for Aggressive Large B-cell NHL.

Background: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphomas (B-NHL) though the majority of recipients do not receive durable disease benefit, prompting the need to better define risk factors for relapse/progression.

Objectives: We performed a single-center, retrospective analysis of patients treated with commercial CAR T-cell therapy to evaluate the impact of tumor burden, as measured by whole-body metabolic tumor volume (MTV) from F fluorodeoxyglucose PET imaging, on treatment outcomes.

Study Design: Sixty-one patients treated with CAR T-cell therapy for R/R B-NHL between May 2016 and November 2021 were included.

TIGIT is a key inhibitory checkpoint receptor in lymphoma.

Background: PD-1 checkpoint blockade therapy (CBT) has greatly benefited patients with select solid tumors and lymphomas but has limited efficacy against diffuse large B-cell lymphoma (DLBCL). Because numerous inhibitory checkpoint receptors have been implicated in driving tumor-specific T cell dysfunction, we hypothesized that combinatorial CBT would enhance the activity of anti-PD-1-based therapy in DLBCL. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a coinhibitory receptor expressed on dysfunctional tumor-infiltrating T cells, and TIGIT blockade has demonstrated encouraging activity in combination with PD-1 blockade in murine tumor models and in clinical studies.

Antigen-Multimers: Specific, Sensitive, Precise, and Multifunctional High-Avidity CAR-Staining Reagents.

Although chimeric antigen receptor (CAR) T-cell therapy has transformed cancer treatment, high-quality and universal CAR-staining reagents are urgently required to manufacture CAR T cells, predict therapy response, decipher CAR biology, and engineer new CARs. Here, we developed tetrameric and dodecameric forms of a multifunctional and extensible category of high-avidity CAR-staining reagents: antigen-multimers. Antigen-multimers detected CARs against CD19, HER2, and Tn-glycoside with significantly higher specificity, sensitivity, and precision than existing reagents.

TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients.

Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8 cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in patients with AML. Natural killer (NK) cells are central players in AML-targeting immune responses.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma.

The recent development and clinical implementation of novel immunotherapies for the treatment of Hodgkin and non-Hodgkin lymphoma have improved patient outcomes across subgroups. The rapid introduction of immunotherapeutic agents into the clinic, however, has presented significant questions regarding optimal treatment scheduling around existing chemotherapy/radiation options, as well as a need for improved understanding of how to properly manage patients and recognize toxicities. To address these challenges, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts in lymphoma to develop a clinical practice guideline for the education of healthcare professionals on various aspects of immunotherapeutic treatment.

Recommendations and outcomes from a geriatric assessment guided multidisciplinary clinic prior to autologous stem cell transplant in older patients.

Background: Autologous hematopoietic stem cell transplant (autoHCT) is a mainstay of treatment for multiple myeloma and non-Hodgkin lymphoma but is underutilized in older adults. We investigated the association of vulnerabilities identified by a geriatric assessment (GA)-guided multidisciplinary clinic (MDC) on the receipt of autoHCT and evaluated its ability to predict outcomes in older autoHCT candidates.

Methods: Patients 50+ years received GA-informed optimization recommendations: 'decline' if unlikely to realize benefits of autoHCT, 'defer' if optimization necessary before autoHCT, and 'proceed' if autoHCT could proceed without delay.

Calreticulin arms NK cells against leukemia.

Calreticulin (CALR) exposed on the surface of cancer cells succumbing to therapy delivers robust phagocytic signals that support the activation of adaptive anticancer immune responses. Recent data from our group demonstrate that spontaneous CARL exposure on leukemic blasts also supports innate anticancer immunity by natural killer (NK) cells via an indirect mechanism relying on myeloid CD11cCD14 cells.

Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients.

In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission of danger signals in the form of damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates that danger signals play a crucial role in the (re-)activation of antitumor immune responses , thus having a major impact on patient prognosis. We have previously demonstrated that the presence of calreticulin on the surface of malignant blasts is a positive prognostic biomarker for patients with acute myeloid leukemia (AML).

Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2.

Background: Dual translocation of MYC and BCL2 or the dual overexpression of these proteins in patients with aggressive B-cell lymphomas (termed double-hit lymphoma [DHL] and double-expressor lymphoma [DEL], respectively) have poor outcomes after chemoimmunotherapy with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Retrospective reports have suggested improved outcomes with dose-intensified regimens. In the current study, the authors conducted a phase 1 study to evaluate the feasibility, toxicity, and preliminary efficacy of adding lenalidomide to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with rituximab (DA-EPOCH-R) in patients with DHL and DEL.

Therapeutic activity of high-dose intratumoral IFN-β requires direct effect on the tumor vasculature.

Endogenous type I IFN production after innate immune recognition of tumor cells is critical for generating natural adaptive immune responses against tumors in vivo. We recently have reported that targeting low doses of IFN-β to the tumor microenvironment using tumor-specific mAbs can facilitate antitumor immunity, which could be augmented further with PD-L1/PD-1 blockade. However, sustained high doses of type I IFNs in the tumor microenvironment, which are potently therapeutic alone, may function through distinct mechanisms.

T-cell-depleted allogeneic transplant without donor leukocyte infusions results in excellent long-term survival in patients with multiply relapsed Lymphoma. Predictors for survival after transplant relapse.

We analyzed 67 patients with lymphoma who received alemtuzumab-based conditioning regimens for allogeneic stem cell transplant and no post-transplant DLI. The median age was 54 (24-70), 43% had unrelated donors, 34% had chemotherapy refractory disease, and 25% had an elevated LDH. With a median follow-up for survivors of 35 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 30% and 47%, respectively.

Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review.

Clofarabine, a synthesised adenosine nucleoside, has recently demonstrated single-agent activity in the acute leukaemias. Originally developed to capture the best qualities of cladribine and fludarabine, clofarabine contains halogenated carbons, rendering it resistant to inactivating enzymes and maintaining its stability in acidic environments. Like other adenosine nucleosides, clofarabine acts by inhibiting ribonucleotide reductase and DNA polymerase, thereby depleting the amount of intracellular deoxynucleoside triphosphates available for DNA replication and also resulting in premature DNA chain termination.