Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies.

Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer.

Patients with human immunodeficiency virus (HIV) infection have a high risk of developing virally-mediated cancers. These tumors have several features that could make them vulnerable to immune checkpoint inhibitors (ICIs) including, but not limited to, increased expression of the CTLA-4 and PD-1 checkpoints on their CD4+ T cells. Even so, HIV-positive patients are generally excluded from immunotherapy cancer clinical trials due to safety concerns.

Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials.

: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. : We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability.

Successful implementation of genomically based treatment of chemotherapy refractory peripheral T-cell lymphoma (PTCL).

Background: The treatment of peripheral T-cell lymphoma (PTCL) after failure of standard therapy represents a significant clinical challenge as the best approach has not been defined. The outcomes of patients with peripheral T-cell lymphoma (PTCL) after relapse, in the absence of hematopoietic stem-cell transplantation, are poor with median overall survival is less than six months. Thus, relapsed/refractory PTCL presents an area of unmet medical need.

Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade.

Kaposi sarcoma (KS) is an incurable, human immunodeficiency virus (HIV)-associated malignancy. We reviewed 320 immunotherapy-treated patient records. Seventeen had HIV-associated malignancies, including nine men with KS.

Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.

The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL). However, approximately one-third of patients do not respond to the drug initially. To identify the mechanisms underlying primary ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib-sensitive and ibrutinib-resistant cell lines on ibrutinib treatment.

Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL.

Ibrutinib has generated remarkable responses in patients with chronic lymphocytic leukemia (CLL), including those with an unfavorable cytogenetic profile. However, patients develop resistance, with poor outcomes and no established treatment options. Mutations in and have emerged as main mechanisms of drug resistance, but not all patients carry these mutations.

Frequency, risk factors, and outcomes of central nervous system relapse in lymphoma patients treated with dose-adjusted EPOCH plus rituximab.

Background: Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) is a rare but serious complication that carries a poor prognosis. The use of infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) for frontline treatment of diffuse large B cell lymphoma (DLBCL) is increasing, though little is known about incidence of and risk factors for CNS relapse with this regimen PATIENTS AND METHODS: We completed a chart review of patients with NHL who received EPOCH-R as front line therapy. Data obtained included baseline and treatment characteristics including if patients received CNS directed therapy.

Emerging role of checkpoint blockade therapy in lymphoma.

Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease.

Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL.

Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naïve chronic lymphocytic leukemia (CLL). However, about 25% of patients discontinue ibrutinib therapy at a median follow-up of 20 months and many patients discontinue the treatment due to leukemia progression or Richter transformation. Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance.

Analysis of racial variations in disease characteristics, treatment patterns, and outcomes of patients with chronic lymphocytic leukemia.

The impact of race on outcomes of patients with chronic lymphocytic leukemia (CLL), the most common leukemia in the west, is not well studied. We aimed to understand racial variations in clinical and disease characteristics, treatment patterns, and outcomes in patients with CLL. We utilized the Mayo Clinic CLL database to perform an analysis of these characteristics and natural history of non-white (NW) compared to white (W) CLL patients.

The evolving role of lenalidomide in non-Hodgkin lymphoma.

Recent advances in the treatment of patients with non-Hodgkin lymphoma have driven a paradigm shift from standard chemotherapy to an ever-expanding choice of targeted agents and combinations. As an orally bioavailable immunomodulator with antineoplastic, immunologic, and antiproliferative activity in B-cell lymphoma, lenalidomide has emerged as one such option. Lenalidomide demonstrates clinically significant activity with a favorable safety profile as a single agent, as well as in combination therapy.

Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib.

In chronic lymphocytic leukemia (CLL), patients with unmutated immunoglobulin heavy chain variable region gene (UM-CLL) have worse outcomes than mutated CLL (M-CLL) following chemotherapy or chemoimmunotherapy. However, in the era of BCR-targeted therapies, the adverse prognostic impact of unmutated IGHV seems to be diminishing, and there are clinical datasets showing unexpected improved responses in UM-CLL. We investigated the biological differences of BTK activity between these subgroups and further compared the impact of ibrutinib on molecular and cellular behaviors.

Molecular predictors of response to therapy for breast cancer.

For several decades, measurements from tumor tissue biomarkers have been used to identify subsets of breast cancer patients that may benefit from specific therapies. Since the 1980s, estrogen receptor testing has been routinely performed on breast carcinoma samples to determine whether hormonal therapy is indicated. Today, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 testing to guide treatment decisions are standard of care.

Bone Metastasis as the Only Metastatic Site in a Patient with Pancreatic Cancer following Distal Pancreatectomy.

Pancreatic cancer remains a challenge both diagnostically and therapeutically. The typical sites of metastases in pancreatic cancer include the liver and peritoneum. Other less common sites are the lung, brain, kidney, and bone.

Blood glucose levels before and after cognitive testing in diabetes mellitus.

The primary indices of diabetes mellitus (DM), including hemoglobin A1c (HbA1c) and fasting glucose, appear to be only moderately predictive of the cognitive impairments exhibited by patients with DM. There is evidence that in DM the ability to utilize glucose is compromised and the authors hypothesized that this difficulty might be relevant to the study of cognitive function in DM. Thus, the authors examined the relationship between cognitive performance and changes in peripheral glucose from the start to the conclusion of cognitive testing.