Bendamustine and Rituximab: Complete Response in a 62-Year-Old Female with an Aggressive Lymphoma and an Ejection Fraction of 20.

The treatment of diffuse large B-cell lymphoma in the presence of cardiac comorbidities can be challenging considering that the standard treatment regimen used for this aggressive subtype of non-Hodgkin lymphoma (NHL) consists of a combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, Oncovin (vincristine), and prednisone (R-CHOP). The use of the anthracycline doxorubicin has been associated with arrhythmias and cardiomyopathy, making patients with cardiac dysfunction poor candidates for R-CHOP. As such, it is imperative to find alternative regimens that omit cardiac toxicity without compromising efficacy for this patient population. We report a case of composite NHL in a patient who received frontline bendamustine with rituximab with encouraging results. Our patient had a left ventricular ejection fraction of 20%, making her a poor candidate for anthracycline-based therapy. We opted to administer bendamustine with rituximab for a total of 6 cycles. She remains disease free 18 months after the completion of therapy.

Durable Response to Venetoclax Monotherapy in Richter's Syndrome: A Case Report and Review of Literature.

In 2017, 20,110 people in the United States were diagnosed with chronic lymphocytic leukemia (CLL). Of these patients, 5-15% will ultimately undergo Richter's syndrome (RS), a transformation to a more aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) type. Particularly when the transformation is clonally related, prognosis is poor in these individuals with a median survival of only 5 - 14 months. This is an area of unmet need, and as such, the benefits of novel approaches with targeted therapies should be explored. Our patient is a 70-year-old female who was diagnosed with CLL in 2010. In 2016, she presented to her general practitioner with new B symptoms and leukocytosis. Cytogenetics on peripheral blood was notable for known trisomy 12 (52.8% of cells) and new 17p deletion (93.4% of cells). She received five cycles of ofatumumab with complete resolution of systemic symptoms but mixed response on interim computed tomography (CT) scan with ensuing rise in her white blood cell (WBC) and lactic acid dehydrogenase (LDH). A positron emission tomography (PET) scan had disproportionate uptake in the porta hepatis lymph nodes and subsequent lymph node biopsy confirmed transformation. She was started on R-CHOP chemotherapy but tolerated it very poorly. She was transitioned to venetoclax monotherapy in April 2017 and achieved a partial response by CT and bone marrow biopsy. This has been maintained over the last 12 months allowing the patient to travel and maintain a high quality of life. While the pathogenesis to RS is poorly understood, there have been several studies to identify tumor genetic changes predisposing to transformation. Of the proposed factors, a review of the literature consistently suggests p53 tumor suppressor gene mutation and/or 17p deletion to be associated with RS. Venetoclax is a selective BCL-2 inhibitor that is now approved for CLL patients with 17p deletion. This case serves as an example encouraging the use and study of novel agents such as venetoclax alone or in combination with traditional regimens or other novel agents to mitigate the poor prognosis of 17p deletion associated RS. Further research, however, is required to clarify the pathogenesis of RS and identify optimal treatment strategies.

Breast implant-associated anaplastic large-cell lymphoma and the role of brentuximab vedotin (SGN-35) therapy: A case report and review of the literature.

Breast implant-associated (BIA) anaplastic large-cell lymphoma (ALCL) is a rare disease, comprising a small percentage of all non-Hodgkin lymphomas (NHLs), reportedly 2-3%. There is currently no established standard approach to the treatment of BIA ALCL. The first case on the development of ALCL in the presence of a breast implant was reported in 1997 and the association was first identified by the Food and Drug Administration in 2011. We herein describe a case of BIA ALCL in a patient with a previous history of breast cancer and breast reconstruction who presented with hardening of her breast implant. The patient underwent capsulectomy and the findings of the pathological examination were consistent with ALCL. The patient completed three cycles of combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP regimen) followed by radiation consolidation therapy, and has maintained a complete remission ever since. The aim of the present study was to review the treatment options for BIA ALCL and suggest an investigation of the CD30-directed antibody-drug conjugate, brentuximab vedotin, as a potential treatment option for BIA ALCL.

All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms.