A Case of Autoimmune Neutropenia That Responded to Rituximab.

Autoimmune neutropenia (AIN) refers to the immune-mediated destruction of neutrophils. It is a rare condition with an estimated prevalence of less than 1 case per 100,000 per year. Typical treatment involves supportive care with granulocyte colony-stimulating factor (G-CSF) and management of secondary infections with antibiotics.

Checkmate 77T: Perioperative chemoimmunotherapy outperforms in early-stage NSCLC.

Approximately 1 in 4 patients with NSCLC present with resectable disease. Although surgery is potentially curative, 30%-50% of patients relapse. Studies have shown that neoadjuvant, adjuvant, and perioperative chemoimmunotherapy improve outcomes.

Assessing Health-Related Quality of Life in Mycosis Fungoides and Sézary Syndrome: Unmet Needs.

Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in MF/SS with a special focus on the gaps in the current knowledge and identify future directions necessary to assess the HRQoL of patients with this disease.

Detangling the Threads of Hairy Cell Leukemia, Beyond the Morphology and Into the Molecular.

Hairy cell leukemia (HCL) makes up 2% of leukemias in the United States and encompasses great molecular heterogeneity. The standard treatment paradigm involves purine nucleoside analogues in the upfront setting with high complete response rate to initial therapy but frequent relapses. There is an increasing role for BRAF inhibitors, with or without rituximab, in refractory and even in untreated patients.

Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis.

Introduction: Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies.

Methods: We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution.

Divarasib in the Evolving Landscape of KRAS G12C Inhibitors for NSCLC.

Kristen Rat Sarcoma viral oncogene (KRAS) mutations are one of the most common oncogenic drivers found in 12-14% of non-small cell lung cancer (NSCLC) and 4% of colorectal cancer tumors. Although previously difficult to target, sotorasib and adagrasib are now approved for previously treated NSCLC patients with KRAS G12C mutations. In preclinical studies, divarasib was 5 to 20 times as potent and up to 50 times as selective as sotorasib and adagrasib.

Taletrectinib for the treatment of positive non-small cell lung cancer: a drug evaluation of phase I and II data.

Introduction: While crizotinib and entrectinib have been approved to treat fusion-positive () non-small-cell lung cancer (NSCLC), unmet needs remain. These unmet needs include treatment options for patients with resistance mutations and efficacious options even in the presence of brain metastasis while simultaneously avoiding unwanted neurological side effects.

Areas Covered: Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation inhibitors; and address central nervous system penetration while conferring fewer neurological adverse events.

The development of amivantamab for the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with sensitizing oncogenic driver mutations benefit from targeted therapies. Tyrosine kinase inhibitors are highly effective against classic sensitizing epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletions and exon 21 L858R point mutations. Conversely, EGFR exon 20 insertions (exon20ins) are resistant to the traditional EGFR tyrosine kinase inhibitors (TKIs).

Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With Advanced - or -Rearranged NSCLC: A Brief Report.

Introduction: Treatment with lorlatinib for patients with advanced - and -rearranged NSCLC (+ and + NSCLC) is associated with a unique set of adverse events (AEs) often requiring dose reduction. However, the impact of dose reductions on outcomes remains unclear and is mainly limited to analyses from prospective studies of lorlatinib in the first-line setting.

Methods: We reviewed the course of 144 patients with advanced or -rearranged NSCLC treated with lorlatinib in the second-line or later setting to assess the frequency of dose reductions resulting from treatment-related AEs (TRAEs) and the association between dose reductions and progression-free survival (PFS) and overall survival (OS).

Multiorgan Failure From Nivolumab and Ipilimumab: A Case Report and Literature Review.

Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and ipilimumab improves treatment efficacy and prolongs survival compared to monotherapy alone. However, combination therapy is also associated with an increased incidence of adverse events.

Pan-tumor survey of RET fusions as detected by next-generation RNA sequencing identified RET fusion positive colorectal carcinoma as a unique molecular subset.

Background: RET fusions are driver alterations in cancer and are most commonly found in non-small cell lung cancer and well-differentiated thyroid cancer. However, RET fusion have been reported in other solid tumors.

Material And Methods: A retrospective analysis of RET+ solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ).

The Additional Exclusions of Fusions (In Addition to Mutation and Fusions) in the Cemiplimab NSCLC FDA Indication (EMPOWER-Lung 1 and -Lung 3). Catching Up with Current Scientific View of Immunotherapy in Never-Smoker Predominant Actionable Driver Mutation Positive NSCLC?

Cemiplimab is one of seven immune checkpoint inhibitors (ICIs) approved for the first-line (1L) treatment of advanced NSCLC in the US based on EMPOWER-Lung 1 and -Lung 3 trials. In addition to exclusion of NSCLC patients harboring mutations and fusion from 1L treatment with ICIs, exclusion of fusion is an additional unique exclusion the use of criterion for cemiplimab in the US FDA indication based on the design of the EMPOWER lung trials. We review the effectiveness of ICIs in never-smoker predominant NSCLC with driver mutations () and question whether exclusion of fusion would put cemiplimab at a competitive disadvantage given the requirement for insurance to prove fusion negativity.

CodeBreaK 200: Sotorasib (AMG510) Has Broken the + NSCLC Enigma Code.

Per the US FDA sotorasib approval summary, mutation is found in approximately 14% of adenocarcinoma of the lung, primarily in patients with a history of smoking. Until recently, targeted therapies against have been largely unsuccessful due to the small protein size of and thus lack of binding pockets in and rapid hydrolysis of GTP to GDP by enzymes from abundance of GTP in the cytoplasm. Sotorasib, a first-in-class covalent inhibitor that binds to the switch pocket II in the -GDP "off" state, received US FDA accelerated approval on May 21, 2021 in the US, based on a Phase II dose expansion cohort of CodeBreaK 100 trial.

SOHO State-of-the-Art Updates and Next Questions: A Modern Approach to the Systemic Treatment of Advanced CTCL.

The term cutaneous T-cell lymphoma (CTCL) is a general term for T-cell lymphomas that are found primarily in skin. The most common CTCL entities, mycosis fungoides and Sezary syndrome are incurable diseases with a plethora of conventional treatment options. In the past treatment options have been selected primarily according to stage.

Tiragolumab (Anti-TIGIT) in SCLC: Skyscraper-02, a Towering Inferno.

Small cell lung cancer (SCLC) is characterized by rapid progression and poor prognosis. Although the phase II CITYSCAPE-02 trial found objective response rate (ORR) and progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients improved when tiragolumab was added to atezolizumab and chemotherapy, the phase III SKYSCRAPER-02 failed to find PFS or OS benefit in patients with SCLC. Atezolizumab was the first immunotherapy to show survival benefit in extensive SCLC based on the phase III IMpower133 study.

Genomic Alterations and Tumor Mutation Burden in Merkel Cell Carcinoma.

Importance: Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma with increasing incidence. Cytotoxic chemotherapy and checkpoint inhibitors provide treatment options in the metastatic setting; however, there are no approved or standard of care targeted therapy treatment options.

Objective: To identify actionable alterations annotated by the OncoKB database therapeutic evidence level in association with tumor mutation burden (TMB).

A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib.

KRAS is one of the most common oncogenes in non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Historically, KRAS mutations have been difficult to target due to lack of binding sites and exceptionally high affinity for guanosine triphosphate/guanosine diphosphate (GTP/GDP). Recently, KRAS selective inhibitors have shown promising results in Phase I/II studies.

Non-small Cell Lung Cancer with EGFR or HER2 Exon 20 Insertion Mutations: Diagnosis and Treatment Options.

Molecular testing is performed upon diagnosis of non-small cell lung cancer (NSCLC) because of the large success of targeted therapies for oncogenic mutations. Epidermal growth factor receptor (EGFR) mutations are the most commonly identified mutation in NSCLC, and EGFR exon 20 insertion mutations (exon20ins) are the third most common mutation in EGFR following EGFR exon 19 deletions and exon 21 L858R mutations. EGFR exon20ins have regularly demonstrated resistance to classical EGFR inhibition.

Stroke in sickle cell disease and the promise of recent disease modifying agents.

Sickle cell disease (SCD) is an inherited hemoglobinopathy affecting approximately 100,000 individuals in the United States. Cerebrovascular disease is among the most common and debilitating complications of SCA, with 53% experiencing silent cerebral infarct by age 30 and 3.8% experiencing overt stroke by age 40 years.

Eponyms in Malignant Hematology.

Eponyms have been traditionally used in the field of medicine to honor the contributions of an individual or group of individuals in understanding a disease. However, many eponyms have come under scrutiny given the personal backgrounds of individuals for whom they intend to honor. As we previously reviewed commonly used eponyms in medical oncology, we now aim to review commonly used eponyms in malignant hematology in order to highlight the individuals for whom they are named after.

Deconstructing ADAURA. It is Not Yet Time to Forgo Platinum-based Adjuvant Chemotherapy in Resected Early Stage (IB-IIIA) EGFR-mutant NSCLC.

Recently, the ADAURA study demonstrated statistically significant improved disease-free survival (DFS) with adjuvant osimertinib in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. A consistent improvement in disease-free survival (DFS) was shown, regardless of whether or not patients received adjuvant chemotherapy. Given benefit seen with and without adjuvant chemotherapy, some clinicians may be tempted to forgo chemotherapy and only offer osimertinib post surgical resection.

Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation.

Mesenchymal-epithelial transition (MET) receptor tyrosine kinase is overexpressed, amplified, or mutated in 1-20% of NSCLC. MET dysregulation is associated with a poor prognosis. Recently, development of targeted therapies against MET exon 14 mutations has demonstrated efficacy and tolerability in early trials.