HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model. Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.

Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial.

BACKGROUND: Platinum-sensitivity is a phenotypic biomarker of Poly (ADP-ribose) polymerase inhibitors (PARPi) sensitivity in histotypes where PARPi are approved. Approximately one-third of non-small cell lung cancers (NSCLC) are platinum-sensitive. The double-blind, randomized phase II PIPSeN (NCT02679963) study evaluated olaparib, a PARPi, as maintenance therapy for patients with platinum-sensitive advanced NSCLC. METHODS: Chemonaïve patients with ECOG performance status of 0-1, platinum-sensitive, EGFR- and ALK-wild-type, stage IIIB-IV NSCLC were randomized (R) to receive either olaparib (O) maintenance or a placebo (P). The primary objective was progression-free survival (PFS) from R. Secondary objectives included overall survival (OS) and safety. With an anticipated hazard ratio of 0.65, 144 patients were required to be randomized, and approximately 500 patients enrolled. RESULTS: The trial was prematurely terminated because anti-PD(L)1 therapy was approved during the trial recruitment. A total of 182 patients were enrolled, with 60 patients randomized: 33 and 27 in the O and P arms, respectively. Patient and tumor characteristics were well-balanced between arms, except for alcohol intake (33% vs 11% in the O and P arms, respectively, p = 0.043). The median PFS was 2.9 and 2.0 months in the O and P arms, respectively (logrank p = 0.99). The median OS was 9.4 and 9.5 months in the O and P arms, respectively (p = 0.28). Grade ≥3 toxicities occurred in 15 and 8 patients in O and P arms, with no new safety concerns. CONCLUSION: PIPSeN was terminated early after enrollment of only 50% of the pre-planned population, thus being statistically underpowered. Olaparib maintenance did neither improve median PFS nor OS in this patient population.

Characterization of a cohort of metastatic lung cancer patients harboring KRAS mutations treated with immunotherapy: differences according to KRAS G12C vs. non-G12C.

Approximately 20% of lung adenocarcinomas harbor activating mutations at KRAS, an oncogene with the ability to alter the tumor immune microenvironment. In this retrospective study, we examined 103 patients with KRAS-mutant lung adenocarcinoma who were treated with immunotherapy-based regimens and we evaluated the clinical outcomes according to PD-L1 expression and the type of KRAS mutation. Among all patients included, 47% carried KRAS G12C mutation whereas 53% harbored KRAS non-G12C mutations. PD-L1 status was available for 77% of cases, with higher expression among KRAS G12C tumors (p = 0.01). Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of KRAS mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.

SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022).

Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurrent chemo-radiotherapy is the standard of care for LS-SCLC that is not surgically resectable, followed by prophylactic cranial irradiation (PCI) for patients without progression. For extensive-stage (ES)-SCLC, a combination of platinum and etoposide has historically been a mainstay of treatment. Recently, the efficacy of programmed death-ligand 1 inhibitors combined with chemotherapy has become the new front-line standard of care for ES-SCLC. Emerging knowledge regarding SCLC biology, including genomic characterization and molecular subtyping, and new treatment approaches will potentially lead to advances in SCLC patient care.

Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

Psychiatric Admissions in a Large Hospital in Madrid during COVID-19 Lockdown: Was There a Change in Patient Profile?

COVID-19 led to a reorganization of health care in Madrid. The objective of this study is to describe the sociodemographic and clinical profile of psychiatric patients admitted to Gregorio Marañón Hospital during lockdown.

Dynamic changes in circulating tumor DNA assessed by shallow whole-genome sequencing associate with clinical efficacy of checkpoint inhibitors in NSCLC.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit. We applied sWGS on cell-free DNA (cfDNA) extracted from plasma samples of 45 patients with metastatic NSCLC treated with ICIs. Over 150 samples were obtained before ICI treatment initiation and at several time points throughout treatment. From sWGS data, we computed the tumor fraction (TFx) and somatic copy number alteration (SCNA) burden and associated them with ICI benefit and clinical features. TFx at baseline correlated with metastatic lesions at the bone and the liver, and high TFx (≥ 10%) associated with ICI benefit. Moreover, its assessment in on-treatment samples was able to better predict clinical efficacy, regardless of the TFx levels at baseline. Finally, for a subset of patients for whom SCNA burden could be computed, increased burden correlated with diminished benefit following ICI treatment. Thus, our data indicate that the analysis of cfDNA by sWGS enables the monitoring of two potential biomarkers-TFx and SCNA burden-of ICI benefit in a cost-effective manner, facilitating multiple serial-sample analyses. Larger cohorts will be needed to establish its clinical potential.

Impact of chemotherapy and/or immunotherapy on neutralizing antibody response to SARS-CoV-2 mRNA-1237 vaccine in patients with solid tumors.

Patients with solid tumors have been a risk group since the beginning of the SARS-CoV-2 pandemic due to more significant complications, hospitalizations or deaths. The immunosuppressive state of cancer treatments or the tumor itself could influence the development of post-vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received two doses of the mRNA-1237 vaccine, and were compared with a group of 26 non-cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS-CoV-2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients. Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non-cancer groups were significant in individuals without previous SARS-CoV-2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non-cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS-CoV-2 vaccination programs.

Is oligoprogression a potentially curable disease in epidermal growth factor receptor mutant lung adenocarcinoma?

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate with a positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an EGFR mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of EGFR mutant patients.

Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature.

Background: Nivolumab is the first programmed cell death receptor 1 (PD-1) inhibitor approved in China. Compared with chemotherapy, nivolumab has shown advantages of good efficacy and safety in the treatment of a variety of tumors. However, due to its short time of use in China and lack of safety experience, clinical understanding of its adverse reactions has not been sufficiently elucidated. In recent years, cases of diabetic ketoacidosis caused by nivolumab have been reported in the emergency department, which has aroused our concern. Case Description: Here we present a serious case of diabetic ketoacidosis in a 69-year-old woman with invasive mucinous adenocarcinoma of the lung, which occurred following therapy with the PD-1 inhibitor nivolumab and dendritic cell/cytokine-induced killer cell (DC/CIK) immunotherapy. She presented with diabetic ketoacidosis 5 days after the second cycle of nivolumab administration. The patient presented with dry mouth symptoms, a maximum blood glucose of 511.2 mg/dL, hemoglobin A1c (HbA1c) level of 7.4%, urine ketone body value of 3+, and extracellular fluid residual alkali level of -3.8 mmol/L. Normal saline and insulin was initiated. The patient had no history of obesity or family history of diabetes. She received a single dose of 3.75 mg of dexamethasone treatment during this period of time which resulted in cough improvement, but did not explain the onset of the diabetes. She was treated with insulin, sitagliptin phosphate tablets and acarbose tablets. Diabetic ketoacidosis was considered an immune-related toxicity caused by nivolumab, and consequently, treatment with nivolumab was suspended. Patient was maintained under insulin treatment with a blood glucose levels normalization. Conclusions: The incubation period of nivolumab-induced diabetic ketoacidosis is dispersive and the clinical risk is high. Patients need life-long insulin therapy. Blood glucose and HbA1c should be monitored routinely before and during nivolumab immunotherapy to avoid the occurrence of diabetic ketoacidosis. After the occurrence of diabetic ketoacidosis, insulin should be used to actively control blood glucose and do a good job in medication education to ensure long-term compliance of patients. Nivolumab should only be initiated if the patient has a clinical benefit under stable glucose control.

Biological and clinical perspectives of the actionable gene fusions and amplifications involving tyrosine kinase receptors in lung cancer.

Identifying molecular oncogenic drivers is crucial for precision oncology. Genetic rearrangements, including gene fusions and gene amplification, involving and activating receptor tyrosine kinases (RTKs) are recurrent in solid tumors, particularly in non-small cell lung cancer. Advances in the tools to detect these alterations have deepened our understanding of the underlying biology and tumor characteristics and have prompted the development of novel inhibitors targeting activated RTKs. Nowadays, druggable oncogenic rearrangements are found in around 15% of lung adenocarcinomas. However, taken separately, each of these alterations has a low prevalence, which poses a challenge to their diagnosis. The identification and characterization of novel targetable oncogenic rearrangements in lung cancer continue to expand, as shown by the recent discovery of the CLIP1-LTK fusion found in 0.4% of lung adenocarcinomas. While tyrosine kinase inhibitors that block the activity of RTKs have represented a breakthrough in the therapeutic landscape by improving the prognosis of this disease, prolonged treatment inevitably leads to the development of acquired resistance. Here, we review the oncogenic fusions and gene amplifications involving RTK in lung cancer. We address the genetic and molecular structure of oncogenic RTKs and the methods to diagnose them, emphasizing the role of next-generation sequencing technologies. Furthermore, we discuss the therapeutic implications of the different tyrosine kinase inhibitors, including the current clinical trials and the mechanisms responsible for acquired resistance. Finally, we provide an overview of the use of liquid biopsies to monitor the course of the disease.

Preoperative Diagnosis and Molecular Characterization of Gliomas With Liquid Biopsy and Radiogenomics.

Gliomas are a heterogenous group of central nervous system tumors with different outcomes and different therapeutic needs. Glioblastoma, the most common subtype in adults, has a very poor prognosis and disabling consequences. The World Health Organization (WHO) classification specifies that the typing and grading of gliomas should include molecular markers. The molecular characterization of gliomas has implications for prognosis, treatment planning, and prediction of treatment response. At present, gliomas are diagnosed via tumor resection or biopsy, which are always invasive and frequently risky methods. In recent years, however, substantial advances have been made in developing different methods for the molecular characterization of tumors through the analysis of products shed in body fluids. Known as liquid biopsies, these analyses can potentially provide diagnostic and prognostic information, guidance on choice of treatment, and real-time information on tumor status. In addition, magnetic resonance imaging (MRI) is another good source of tumor data; radiomics and radiogenomics can link the imaging phenotypes to gene expression patterns and provide insights to tumor biology and underlying molecular signatures. Machine and deep learning and computational techniques can also use quantitative imaging features to non-invasively detect genetic mutations. The key molecular information obtained with liquid biopsies and radiogenomics can be useful not only in the diagnosis of gliomas but can also help predict response to specific treatments and provide guidelines for personalized medicine. In this article, we review the available data on the molecular characterization of gliomas using the non-invasive methods of liquid biopsy and MRI and suggest that these tools could be used in the future for the preoperative diagnosis of gliomas.

A Randomized, Open-Label Phase II Study Evaluating Emibetuzumab Plus Erlotinib and Emibetuzumab Monotherapy in MET Immunohistochemistry Positive NSCLC Patients with Acquired Resistance to Erlotinib.

INTRODUCTION: The hepatocyte growth factor receptor MET represents a resistance mechanism to epidermal growth factor receptor (EGFR) inhibition in EGFR mutant (mt) non-small cell lung cancer (NSCLC). This Phase 2 study tested whether acquired resistance to erlotinib in MET protein positive NSCLC patients enriched for EGFRmt can be overcome by emibetuzumab plus erlotinib. PATIENT AND METHODS: Patients with Stage IV NSCLC with acquired resistance to erlotinib and MET diagnostic (+) (≥ 10% of cells expressing MET at ≥ 2+ IHC staining intensity at any time) were randomized (3:1) to receive emibetuzumab 750 mg every 2 weeks with or without erlotinib 150 mg once daily. The primary objective was to evaluate the overall response rate (ORR) relative to historic control, with a co-primary objective of ORR in patients with MET expression in ≥ 60% of cells ≥ 2+ (MET ≥ 60%). RESULTS: One hundred and eleven MET+ patients received emibetuzumab plus erlotinib (N = 83) or emibetuzumab monotherapy (N = 28). 89 of 111 MET+ samples were post-erlotinib. ORR was 3.0% for emibetuzumab plus erlotinib (95% CI: 0.4, 10.5) and 4.3% for emibetuzumab (95% CI: 0.1, 21.9), in patients with post-erlotinib progression biopsies available (n = 89). Similar results were observed in patients with MET ≥ 60% expression (n = 74). Disease control rate and progression-free survival were higher for emibetuzumab plus erlotinib (50%/3.3 months) than for emibetuzumab (26%/1.6 months). No unexpected safety signals emerged. Partial responses were observed in patients with and without EGFRmt or MET amplification. EGFR sensitizing mutations were identified retrospectively in 84.2% of those with available tissue (85/101). CONCLUSION: Acquired resistance to erlotinib in MET diagnostic (+) patients was not reversed by emibetuzumab plus erlotinib or emibetuzumab monotherapy, although a subset of patients obtained clinical benefit.

Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Background: Despite the emergence of programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs), knowledge gaps remain regarding the impact and timing of cranial radiotherapy for patients receiving anti-PD-1/PD-L1 therapy. Methods: Data were collected from 461 consecutive patients who received anti-PD-1/PD-L1 therapy for metastatic NSCLC at three institutions between June 2017 and September 2020. Intracranial progressive disease (PD) at the original disease sites, new sites, or both sites were classified as original-site PD (OPD), new-site PD (NPD), and original-and-new-site PD (ONPD), respectively. Patients with baseline BMs were categorized based on whether they received upfront cranial radiotherapy (uCRT) at any time point between the introduction of anti-PD-1/PD-L1 therapy and the first subsequent progression. Results: Of the 461 patients enrolled, 110 (23.9%) had BMs at baseline. The presence of BMs did not show independent prognostic value for progression-free survival (PFS) or overall survival (OS). During a median follow-up of 13.2 months, 96 patients with BMs developed PD, of whom 53 (55.2%) experienced intracranial PD. OPD, NPD, and ONPD were observed in 50.9%, 18.9%, and 30.2% of patients, respectively. Patients who received uCRT exhibited a longer median OS than those with BMs who did not receive uCRT (25.4 vs. 14.6 months, HR: 0.52, 95% CI: 0.29-0.91, P=0.041); this survival advantage was more prominent in patients with 1-4 BMs (median OS, 25.4 vs. 17.0 months, HR: 0.42, 95% CI: 0.22-0.81, P=0.024), and uCRT was independently associated with OS among these patients. Conclusions: The presence of BMs at baseline was not associated with poorer OS in patients with metastatic NSCLC treated with anti-PD-1/PD-L1 therapy. Intracranial progression on PD-l/PD-L1 inhibitors predominately occurred at the original BM sites. The use of uCRT may improve OS, especially in NSCLC patients with 1-4 BMs.

Modulation of DNA Damage Response by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase (SAMHD1) Determines Prognosis and Treatment Efficacy in Different Solid Tumor Types.

SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase with important roles in the control of cell proliferation and apoptosis, either through the regulation of intracellular dNTPs levels or the modulation of the DNA damage response. However, SAMHD1's role in cancer evolution is still unknown. We performed the first in-depth study of SAMHD1's role in advanced solid tumors, by analyzing samples of 128 patients treated with chemotherapy agents based on platinum derivatives and/or antimetabolites, developing novel in vitro knock-out models to explore the mechanisms driving SAMHD1 function in cancer. Low (or no) expression of SAMHD1 was associated with a positive prognosis in breast, ovarian, and non-small cell lung cancer (NSCLC) cancer patients. A predictive value was associated with low-SAMHD1 expression in NSCLC and ovarian patients treated with antimetabolites in combination with platinum derivatives. In vitro, SAMHD1 knock-out cells showed increased γ-H2AX and apoptosis, suggesting that SAMHD1 depletion induces DNA damage leading to cell death. In vitro treatment with platinum-derived drugs significantly enhanced γ-H2AX and apoptotic markers expression in knock-out cells, indicating a synergic effect of SAMHD1 depletion and platinum-based treatment. SAMHD1 expression represents a new strong prognostic and predictive biomarker in solid tumors and, thus, modulation of the SAMHD1 function may constitute a promising target for the improvement of cancer therapy.

Comparison between standard and wide-field autofluorescence in detection of retinal displacement after rhegmatogenous retinal detachment surgery.

Purpose: To analyse the differences between 30° blue autofluorescence (BAF30), 55° blue autofluorescence (BAF55) and 200° green Ultra-Wide Field autofluorescence (UWF200) imaging to detect retinal displacement (RD) after vitrectomy surgery for rhegmatogenous retinal detachment (RRD). Methods: This cross-sectional study considers forty-nine consecutive patients who underwent RRD surgery in the time period 4-8 months previous to image acquisition. The exclusion criteria contemplate previous retinal pathology, under 18-year-olds and non-assessable images in any of the 3 devices. These images were analysed by two masked graders that assessed either the presence or absence of retinal displacement. A third observer reviewed the images that presented discordance. Results: A total of forty-nine patients were analysed. 7 eyes were excluded due to poor quality in either of the imaging modalities. The final analysis included 42 eyes of forty-two patients with a mean age of 60.3 â€‹± â€‹11.9 years. All patients underwent a 3 port 23-gauge pars plana vitrectomy as the technique of choice. Any grade of RD was detectable in 45.2% of images. It was similar between BAF30 and UWF200 (42.9% of eyes). BAF55 showed RD to a lesser extent (38.1%). Agreement index between BAF30 and BAF55 was 0.901, 0.903 between BAF30 and UWF200 and 0.803 between BAF55 and UWF200. Kappa agreement index between graders was 0.775 for BAF30, 0.798 for BAF50 and 0.808 for UWF200 images. Conclusions: All imaging modalities were able to detect RD after vitrectomy for RRD, with no inferiority of BAF30 and BAF55 over UWF200.

Effect of CD4+ T cell count on treatment-emergent adverse events among patients with and without HIV receiving immunotherapy for advanced cancer.

BACKGROUND: The Food and Drug Administration recommends that people living with HIV (PWH) with a CD4+ T cell count (CD4) ≥350 cells/µL may be eligible for any cancer clinical trial, but there is reluctance to enter patients with lower CD4 counts into cancer studies, including immune checkpoint inhibitor (ICI) studies. Patients with relapsed or refractory cancers may have low CD4 due to prior cancer therapies, irrespective of HIV status. It is unclear how baseline CD4 prior to ICI impacts the proportion of treatment-emergent adverse events (TEAE) and whether it differs by HIV status in ICI treated patients. METHODS: We conducted a pilot retrospective cohort study of participants eligible for ICI for advanced cancers from three phase 1/2 trials in the USA and Spain. We determined whether baseline CD4 counts differed by HIV status and whether the effect of CD4 counts on incidence of TEAE was modified by HIV status using a multivariable logistic regression model. RESULTS: Of 122 participants, 66 (54%) were PWH who received either pembrolizumab or durvalumab and 56 (46%) were HIV-negative who received bintrafusp alfa. Median CD4 at baseline was 320 cells/µL (IQR 210-495) among PWH and 356 cells/µL (IQR 260-470) among HIV-negative participants (p=0.5). Grade 3 or worse TEAE were recorded among 7/66 (11%) PWH compared with 7/56 (13%) among HIV-negative participants. When adjusted for prior therapies, age, sex, and race, the effect of baseline CD4 on incidence of TEAE was not modified by HIV status for any TEAE (interaction term p=0.7), or any grade ≥3 TEAE (interaction term p=0.1). CONCLUSIONS: There was no significant difference in baseline CD4 or the proportions of any TEAE and grade ≥3 TEAE by HIV status. CD4 count thresholds for cancer clinical trials should be carefully reviewed to avoid unnecessarily excluding patients with HIV and cancer.

Immune Response and Effects of COVID-19 Vaccination in Patients with Lung Cancer-COVID Lung Vaccine Study.

Lung cancer patients represent a subgroup of special vulnerability in whom the SARS-CoV-2 infection could attain higher rates of morbidity and mortality. Therefore, those patients were recommended to receive SARS-CoV-2 vaccines once they were approved. However, little was known at that time regarding the degree of immunity developed after vaccination or vaccine-related adverse events, and more uncertainty involved the real need for a third dose. We sought to evaluate the immune response developed after vaccination, as well as the safety and efficacy of SARS-CoV-2 vaccines in a cohort of patients with lung cancer. Patients were identified through the Oncology/Hematology Outpatient Vaccination Program. Anti-Spike IgG was measured before any vaccine and at 3-6-, 6-9- and 12-15-month time points after the 2nd dose. Detailed clinical data were also collected. In total, 126 patients with lung cancer participated and received at least one dose of the SARS-CoV-2 vaccine. At 3-6 months after 2nd dose, 99.1% of baseline seronegative patients seroconverted and anti-Spike IgG titers went from a median value of 9.45 to 720 UI/mL. At the 6-9-month time point, titers raised to a median value of 924 UI/mL, and at 12-15 months, after the boost dose, they reached a median value of 3064 UI/mL. Adverse events to the vaccine were mild, and no SARS- CoV-2 infection-related deaths were recorded. In this lung cancer cohort, COVID-19 vaccines were safe and effective irrespective of the systemic anticancer therapy. Most of the patients developed anti-Spike IgG after the second dose, and these titers were maintained over time with low infection and reinfection rates with a mild clinical course.