Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant.

PURPOSE: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.

PURPOSE: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. METHODS: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. RESULTS: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. CONCLUSIONS: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

Neoadjuvant and adjuvant treatment approaches for hepatocellular carcinoma: future outlook.

Hepatocellular carcinoma (HCC) is a highly aggressive and chemotherapy resistant cancer with unique biologic characteristics which makes this disease highly different than other gastrointestinal cancers. The mainstay of curative treatment in HCC is surgical resection, ablation, and transplantation. However, rates of recurrence are high and many patients are not initially candidates for these curative approaches. This paper discusses predictors of recurrence of HCC in patients who have undergone surgical resection and addresses adjuvant therapies aimed at decreasing recurrence risk and improving overall survival (OS) outcomes, including traditional cytotoxic chemotherapies, tyrosine kinase inhibitors (TKIs), and immunotherapy. This article also discusses neoadjuvant strategies aimed at improving recurrence rate and OS as well as downstaging advanced HCC to enable surgical disease, including locoregional therapies, systemic chemotherapy, TKIs, and immune checkpoint inhibitors. Finally, this article addresses potential future directions for both adjuvant and neoadjuvant therapies that may change the treatment paradigm of HCC in the near future.

Chronic Myeloid Leukemia as Secondary Malignancy Following the Treatment of Hodgkin Lymphoma: A Case Series.

Secondary malignancies are relatively common and clinically important phenomena following both chemotherapy and radiotherapy. The majority of these cases are acute leukemias, the occurrence of which have been thoroughly documented and studied. More rarely, chronic myeloid leukemias (CML) may arise subsequent to treatment of a primary malignancy. Literature review on such developments following treatment of Hodgkin's Lymphoma (HL) is scant. Herein, the authors present three cases of CML diagnosed within five years of treatment initiation for Hodgkin's Lymphoma (HL); one of the three patients had CML with atypical variant carrying a rare mutation with BCR-JAK2 fusion.

Two distinct histological Richter's transformations 23 years apart in a patient with chronic lymphocytic leukaemia.

A 53-year-old man with a 1-year history of chronic lymphocytic leukaemia (CLL) presented with a left bicep mass. Biopsy and staging workup revealed Richter's transformation (RT) Ann Arbor stage 1E diffuse large B-cell lymphoma in the bicep. The patient was treated with combination chemotherapy with cyclophosphamide, doxorubicin, Vincristine and prednisone followed by site radiation and did well thereafter. His CLL progressed and required treatment on two more occasions 11 and 18 years after his initial diagnosis with fludarabine, Cytoxan and Rituxan and then with bendamustine and rituximab. 23 years after initial presentation, he developed diffuse lymphadenopathy and B-symptoms. A biopsy of an enlarged cervical lymph node demonstrated only CLL for which he was started on ibrutinib. Treatment was shortly discontinued thereafter due to intolerance and worsening symptoms. A second biopsy was performed which revealed concurrent CLL and Hodgkin's lymphoma representing a second and histologically distinct RT.

Directed Therapies in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer.

Anaplastic lymphoma kinase (ALK) rearrangements were first implicated as driving mutations in non-small cell lung cancer in 2007. Since then, a number of novel, small-molecule inhibitors directed against the ALK receptor have demonstrated superiority over standard chemotherapies in the treatment of ALK rearrangement-positive lung cancer. Of considerable importance when considering such therapies is the ability of each to overcome mutations conferring acquired resistance, as well as penetrate the central nervous system (CNS), the most common site of metastasis and traditionally the most difficult to breach. Herein is a review of the efficacy, indications, and degree of CNS penetration for the ALK-targeting agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a summary of ongoing clinical trials comparing these drugs.

Abiraterone is effective and should be considered for the treatment of metastatic castrate-naïve prostate cancer.

INTRODUCTION: Androgen deprivation therapy (ADT) has been the standard of care for the treatment of newly diagnosed metastatic prostate cancer for the past 70 years. Furthermore, adding docetaxel chemotherapy to ADT significantly improved patient survival, and thus became the new standard for patients with high volume disease. However, recent evidence has called this treatment strategy into question since a published study has shown that the drug abiraterone has a similar benefit to docetaxel in a similar patient population group but with less toxicity. The following article considers this key paper and its implications. Areas covered: In this key paper evaluation, the authors discuss the rational, trial design and results of the LATITUDE trial. Furthermore, the past and current standard of care of metastatic castrate-naïve prostate cancer (mCNPC) is discussed, while the authors also compare abiraterone and docetaxel in terms of benefit, safety profile, and affordability. Expert opinion: Abiraterone is highly effective and has an excellent safety profile for the treatment of metastatic castrate-naïve prostate cancer. It is the authors' opinion that it should now be considered the new standard of care.