-
Mashup Score: 56
Background Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse. Methods This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial were extracted (KN024 IPD cohort) to compare the long-term outcomes between the two cohorts. To further assess the reproducibility of clinical trial results, we reconstructed the “KN024 look-alike” cohort by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS)≥2, those requiring corticosteroids with doses ≥10 mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet
-
Mashup Score: 5132 Racial differences in TMB measures between paired tumor/normal and tumor-only sequencing across endometrial, bladder, and non-small cell lung cancers - 1 month(s) ago
Background Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of a tumor, is routinely used as a predictive biomarker for immunotherapy response in metastatic cancer patients. Sequencing of paired tumor and normal specimens allows for correction of TMB estimates with patient-specific germline variants. For tumor only assays, TMB estimates are corrected using germline variant annotations derived from population-scale germline variant surveys. These surveys often underrepresent minorities and individuals of non-European descent, leading to potential inaccuracies in TMB estimates in these populations. Methods Our cohort includes patients who underwent tumor genomic profiling with the Tempus xT Next Generation Sequencing (NGS) assay and diagnosed with non-small cell lung (NSCLC, n=4,583) endometrial (n=3,084), or urothelial (n=2,806) cancer. We used 654 ancestry informative markers selected to overlap the target regions of the 648-gene Tempus xT NGS assa
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Racial differences in TMB measures b/w paired tumor/normal & tumor-only sequencing across endometrial, bladder & non-small cell lung cancers [Nov 7, 2022] @ribozyme et al. @JITC #SITC22 Abs 132 https://t.co/1g4yPP91uq #PrecisionMedicine #ImmunoOnc #gyncsm #blcsm @lcsm @TempusLabs
-
-
Mashup Score: 8Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma - 1 month(s) ago
Background Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (TCM) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context. Methods The clinical trial ([NCT04176380][1]) evaluated RAPA-201 therapy in combination with fludarabine-sparing low-dose host conditioning for the treatment of patients with relapsed, refractory multiple myeloma (RRMM). Results From December 2020 to December 2022, 14 patients with RRMM received a median of three RAPA-201 infusions (median dose, 80×106 cells). RAPA-201 drug products (DPs) were: polyclonal; enriched for TCM cells; reduce
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma | Journal for ImmunoTherapy of Cancer @MCWCancerCenter @Chhabra_mayo @Phari https://t.co/b7PUaeJEL2
-
-
Mashup Score: 9
The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response. Tumor neoantigens are de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance of self-epitopes and inducing immune responses to tumors. The identification and prioritization of patient-specific tumor neoantigens are based on advanced computational algorithms taking advantage of the profiling with next-generation sequencing considering factors involved in human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. This review discusses the development and
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Had a terrific time collaborating with Wei Zheng, Sisi Sarkizova (@moderna_tx) and @mceccarelli (@SylvesterCancer) for a review on mRNA-based neoantigen-directed cancer immunotherapy, now available from @jitcancer https://t.co/k30FF497Ca
-
-
Mashup Score: 297Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade - 2 month(s) ago
Background Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy. Methods From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins. Patients were stratified by obesity status at treatment initiation, with obesity defined as body mass index (BMI)≥30 at treatment initiation and BMI≥18.5 and <30 considered non-obese; underweight patients (BMI<18.5) were excluded. We evaluated the concentration of 37 cytokines and used cytometry by time of flight to characterize im
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Our first 2025 paper was published today in JITC Explores the "obesity paradox" in cancer immunotherapy: 1️⃣ Obese patients have better IO outcomes (despite ⬆️cancer risk) 2️⃣ Obesity → ⬆️T-cell exhaustion →⬆️ ICI benefit https://t.co/0VFM1YpFF3 https://t.co/afX32qFqMw
-
-
Mashup Score: 276Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade - 2 month(s) ago
Background Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy. Methods From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins. Patients were stratified by obesity status at treatment initiation, with obesity defined as body mass index (BMI)≥30 at treatment initiation and BMI≥18.5 and <30 considered non-obese; underweight patients (BMI<18.5) were excluded. We evaluated the concentration of 37 cytokines and used cytometry by time of flight to characterize im
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Our first 2025 paper was published today in JITC Explores the "obesity paradox" in cancer immunotherapy: 1️⃣ Obese patients have better IO outcomes (despite ⬆️cancer risk) 2️⃣ Obesity → ⬆️T-cell exhaustion →⬆️ ICI benefit https://t.co/0VFM1YpFF3 https://t.co/afX32qFqMw
-
-
Mashup Score: 10
In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment of patients with metastatic melanoma. The infusion of autologous tumor-infiltrating T lymphocytes (TIL) is capable of mediating durable tumor regression and is now Food and Drug Administration-approved for patients with disease refractory to immune checkpoint inhibitors. Since the advent of chimeric antigen receptor (CAR) T cells for patients with hematological malignancies, a growing network of centers capable of delivering effector T cell products to patients has developed. Administration of TIL can be layered onto that institutional framework, but there are many complex and unique aspects to TIL immunotherapy. The highly multidisciplinary clinical expertise and coordination required to successfully and safely deliver TIL to patients began within the National Cancer Institute Surgery Branch and have been subsequently adopted worldwide. The general steps, most of which require hospital i
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
RT @DoniaMarco: The art of TIL therapy: Perspective from @sitcancer 👉Free access https://t.co/5aETNaOA3S at @jitcancer https://t.co/0V0fUT…
-
-
Mashup Score: 15Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma - 3 month(s) ago
The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient’s own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases. Age profoundly affects the physiological function of the immune system. The process of biological aging is largely driven by inflammatory signaling, which is reciprocally fueled by aging-related alterations of physiology and metabolism. In the T cell compartment, aging contributes to T cell senescence and exhaustion, increased abundance of terminally differentiated cells, a corresponding attrition in naïve T cell numbers, and a decrease in the breadth of the receptor repertoire. Furthermore
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
🚨 HOT OFF THE PRESS!! Impact of immunological #aging on T cell-mediated therapies in older adults 👴👵 with multiple #myeloma and #lymphoma #hematology 🩸 #lymsm #mmsm #ImmunoOnc https://t.co/QRvDmlsTb9
-
-
Mashup Score: 1FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy - 3 month(s) ago
Background The role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab. For enrollment in track 2 (reported here), patients with histologically confirmed clear cell aRCC, Karnofsky performance status ≥70%, and life expectancy ≥3 months who had previously progressed after IO (anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)) therapy were eligible. Previous treatment with anti-CTLA-4 therapy plus anti-PD-1/PD-L1 therapy precluded eligibility for enrollment in the n
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
4/Our findings from pts who had received previous anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy were reported separately: (https://t.co/1glCWxWJRj)
-
-
Mashup Score: 0Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma - 3 month(s) ago
Background Immune checkpoint inhibitors (ICIs) are becoming the standard of care for recurrent and metastatic cancer. Opioids, the primary treatment for cancer-related pain, are immunosuppressive raising concerns about their potential to interfere with the efficacy of ICIs. We hypothesize that exogenous opioids given for analgesia suppress antitumor immunity via T cell-mediated mu opioid receptor 1 (OPRM1) signaling. Methods In silico bioinformatics were used to assess OPRM1 receptor expression on tumor-infiltrating immune cells in patients with head and neck squamous cell carcinoma (HNSCC) and across different cancer types. A syngeneic orthotopic mouse model of oral squamous cell carcinoma was used to study the impact of morphine and OPRM1 antagonism on tumor-infiltrating immune cells, tumor growth and antitumor efficacy of anti-Programmed cell death protein 1 (PD-1) monoclonal antibody treatment. Results In patients with HNSCC, OPRM1 expression was most abundant in CD8+ T cells, part
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma https://t.co/8ypxdLaubj
-
Congrats to @ACortelliniMD et al on this global RWE study evaluating 5yr OS in adv PDL1>50% NSCLC from pembrolizumab @jitcancer: - 1050pts, 61 centres - 5yr OS 26.9%, mOS 21.8m, 3% CR - majority of pts stop for PD (64.9%), or tox (15.4%) @OncoAlert #LCSM https://t.co/QUpyrSzgXM