Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma.

INTRODUCTION: Chimeric antigen receptor T (CAR T) cell therapy epitomizes the success of T cell engineering. Today, it is an integral component of the treatment algorithm for various types of B-cell non-Hodgkin lymphoma (NHL). Large B-cell lymphoma (LBCL) is the most common subtype of NHL accounting for 30-35% of cases. A lack of response to second-line therapy portends a poor prognosis as only 7-15% of patients attain complete remission (CR) with subsequent conventional chemoimmunotherapy. AREAS COVERED: Lisocabtagene maraleucel (liso-cel) is an autologous CD-19 directed CAR T-cell product with a 4-1BB co-stimulatory domain administered as a sequential infusion of 2 separately manufactured components: CD8+ and CD4+ CAR T-cells in equal doses. Liso-cel showed an impressive objective response rate of 73% (CR = 53%) in patients who had received a median of 3 prior therapies. Median time-to-first CR or partial response (PR) was 1 month. EXPERT OPINION: When evaluated in the second line setting in LBCL, liso-cel demonstrated superior event-free survival (EFS) versus standard of care. While acknowledging that choice of a particular CAR T-cell is based chiefly on familiarity of the treating physician with a specific product, liso-cel definitely represents an important addition to the treatment armamentarium of R/R LBCL whether in the second-line setting or beyond.

Clinical Utility of Azacitidine in the Management of Acute Myeloid Leukemia: Update on Patient Selection and Reported Outcomes.

Acute myeloid leukemia (AML) is predominantly a disease of the elderly, and a significant proportion of these patients are not candidates for intensive, curative-intent therapies. Epigenetic dysregulation resulting in abnormal DNA hypermethylation is one of the hallmarks of AML pathogenesis. For the past two decades, hypomethylating agents including azacitidine (AZA) have been the mainstay of treatment for AML patients who are ineligible to receive intensive chemotherapies. As our understanding of AML disease biology has improved, several novel treatment combinations have been developed to improve the outcome of AML patients, with remarkable success. A considerable proportion of these novel combinations have utilized AZA as the backbone of their treatment scheme. In this review, we have highlighted the evolution of AML treatment, focusing on novel AZA-based treatment combinations and their clinical efficacy.

Malignancy-induced lactic acidosis in adult lymphoma.

Malignancy-induced lactic acidosis (MILA), a rare paraneoplastic phenomenon, is mostly described with hematologic malignancies (lymphomas and leukemias) but has also been reported with solid tumors. It is a subset of type B lactic acidosis being mediated without evidence of tissue hypoperfusion. Lymphoma-induced lactic acidosis is often considered an oncologic emergency and is associated with an increased risk of mortality and poor prognosis. It has a complex pathophysiology centered in the "Warburg effect," i.e., the programming of cancer cells to depend on aerobic glycolysis for promotion of their proliferation and anabolic growth. The treatment of lymphoma-induced lactic acidosis is focused on prompt administration of chemotherapy. The role of alkali therapy in this setting is controversial and has limited proven benefit with a potential for worsening the lactic acidosis. If alkali therapy is used in the presence of severe acidemia to optimize cardiovascular status, it should be administered judiciously.

Multimodality therapy of endometrial glassy cell carcinoma: a rare type of cancer.

Glassy cell carcinoma (GCC) is a rare histologically aggressive cancer subtype of the cervix that is associated with poor prognosis. Only 16 cases of endometrial GCC (EGCC) have been described in the literature to date. The data on prognostic factors and management of EGCC are limited and no optimal treatment protocol has been established. We describe a case of a 67-year-old woman who presented with postmenopausal bleeding and was diagnosed with stage IA EGCC. The patient's risk factors included histology, age and lower uterine segment involvement. The patient was successfully treated with total hysterectomy and bilateral salpingo-oophorectomy with pelvic node dissection followed by adjuvant sandwich chemotherapy and radiotherapy. The patient has no evidence of disease recurrence for 18 months. This is the first case of EGCC management with adjuvant multimodality therapy.

Post-transplant erythrocytosis refractory to ACE inhibitors and angiotensin receptor blockers.

Post-transplant erythrocytosis (PTE) is a condition with elevated haematocrit (hct) in renal allograft recipients. The mainstay of treatment is ACE inhibitors (ACEi) or angiotensin II receptor blockers (ARB), but seldom phlebotomy. PTE must be recognised early to prevent major thromboembolic events. We present a case of PTE that was refractory to blockade of renin-angiotensin system (RAS) by ACEi and ARB and required phlebotomy for control of hct. Our review of medical literature about prevalence and pathophysiology of PTE suggests that approximately 22% of patients with PTE are refractory to ACEi/ARB treatment. There are four plausible pathways that appear to play a role in causing PTE: disruption of erythropoietin regulation, mitogenic effect of the RAS on erythroid lineage, insulin-like growth factor 1 and androgenic stimulation. Presently, there is no unifying hypothesis involving these factors, but refractoriness to ACEi/ARB may represent a distinct subcategory of PTE.