Systemic immunoglobulin light chain (AL) amyloidosis is a rare but fatal disease. It results from clonal proliferation of plasma cells with excessive production of insoluble misfolded proteins that aggregate in the extracellular matrix, causing damage to the normal architecture and function of various organs. For decades, treatment for AL amyloidosis was based mainly on therapeutic agents previously studied for its more common counterpart, multiple myeloma. As the prevalence and incidence of AL amyloidosis have increased, ongoing research has been conducted with treatments typically used in myeloma with varying success. In this review, we focus on current treatment strategies and updates to clinical guidelines and therapeutics for AL amyloidosis.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin's lymphoma with a dismal prognosis. The pathogenesis almost invariably involves Epstein-Barr virus (EBV) infection, although EBV-negative ENKTLs are frequently reported in the western hemisphere. Treatment of these lymphomas consists of aggressive chemotherapy with dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE regimen). However, the SMILE regimen is poorly tolerated by elderly patients; therefore, treatment options are limited to palliative radiation and chemotherapy and/or hospice care. Recently, binding of programmed death (PD)-1 with its ligand (PD-L1) expressed on tumor cells was shown to downregulate effector T-cell function and may represent a potent mechanism of immune evasion in classical Hodgkin's lymphoma and aggressive B-cell lymphomas. Thus, targeting PD-L1/PD-1 to inhibit effector T-cell signaling may be a promising therapeutic strategy for these NK/T-cell lymphomas. We herein report the clinical efficacy and feasibility of the anti-PD-1 inhibitor pembrolizumab used concurrently with radiation therapy and as maintenance therapy in an elderly female patient. The findings demonstrated that pembrolizumab may be an effective and well-tolerated treatment for this type of lymphoma.

Background Hereditary hemochromatosis (HH) is an autosomal recessive disorder affecting iron metabolism, resulting in iron accumulation in tissue parenchymal cells. Missense mutations result in homozygosity or heterozygosity for substitutions in the HFE gene, with the most common being C282Y and H63D. Methods With an aim to evaluate an association between polycythemia and HH, retrospective chart review was performed for 152 patients with known HFE mutations. Parameters reviewed included individual HFE genotypes, gender distribution, hemoglobin (Hgb) and hematocrit (Hct) levels, median ferritin levels and whether or not phlebotomy was required. Results Of 152 patients, 96 (63.2%) were men and 56 (36.8%) were women. Median Hgb and Hct were noted to be higher in men compared to women irrespective of HFE status. Mean age was 60.5 years (range 22 - 93 years). Regarding HFE mutation, 44 (28.9%) patients were C282Y/C282Y, 10 (6.6%) were H63D/H63D and 27 (17.8%) had one copy of each mutation. One patient in the study group was H63D/S65C. Median Hgb and Hct were noted to be 15.5 g/dL and 44.9% respectively in C282Y/C282Y subjects, 16.0 g/dL and 47% in H63D/H63D subjects, 15.8 g/dL and 46% in C282Y/H63D subjects, 16g/dL and 47% in those with single C282Y mutation and 16.6g/dL and 48% in those with single H63D mutation. A total of 67.1% subjects received phlebotomy. A total of 21.7% patients in this cohort were active tobacco users and only 8.6% had an established pulmonary diagnosis, including obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Elevated Hgb levels were noted despite absence of an established reason for secondary polycythemia. Anemia was not encountered despite concurrent medical conditions that would usually be associated with anemia, including gastrointestinal bleeding or end-stage renal disease (ESRD). Conclusions Elevated Hgb and Hct levels in HH may be secondary to increased iron uptake by erythroid cell precursors in the bone marrow, in setting of increased availability of both transferrin-bound as well as non-transferrin-bound iron (NTBI). Additional studies need to be pursued to explore the association between HFE mutations and secondary polycythemia.

Ocular complications of antineoplastic agents can have a profound effect on the quality of life of cancer patients. New oncologic treatments like monoclonal antibodies, immunotherapies, antibody-drug conjugates, checkpoint inhibitors and growth factor receptors have resulted in increased ocular complications. These ocular complications differs in respect to distinct mechanisms of actions and lead to significant challenges in the management of cancer patients. In this review, we reviewed literature, clinical studies and cases detailing ocular complications due to administration of antineoplastic agents and emphasized the need for communication between oncologists and ophthalmologists toward early detection and management of ocular complications.

Introduction: Carfilzomib is a proteasome inhibitor that is known to be associated with cardiotoxicity. Current clinical data on Carfilzomib associated with cardiotoxicity is generated in clinical trials from which patients with severe cardiovascular comorbidities were excluded. In this study, we have reported real-word experience on outcome of cardiotoxicity in patients managed by physicians in a community setting. Methods: We performed a retrospective analysis evaluating for cardiac complications in MM patients who received Carfilzomib at our institution in the last 5 years. Pre- and post-therapy echocardiogram findings were compared. Chi-square tests were used to compare categorical variables with an α level set at 0.05 for statistical significance. Results: Among the 28 identified patients who had pre- and post- Carfilzomib therapy echocardiogram imaging, (18 patients, 64%) had at least one echocardiographic abnormality. The main changes were in heart functions (10/28), whereas systolic dysfunction is seen in 9 patients while only one patient had diastolic dysfunction, pulmonary artery pressure (6/28), and wall motion abnormalities (5/28). (11/28) patients had disease progression. We did not notice any correlation to variables such as; age, duration of therapy, dose differences, and number of lines of therapies. Furthermore, two patients were rechallenged with Carfilzomib after echocardiographic worsening; one of them tolerated the treatment well, while the other had further worsening that led to holding the therapy. Conclusion: Several echocardiographic changes could be related to Carfilzomib therapy. Our study was limited due to the sample size and the retrospective nature of the analysis. Larger studies are needed to detect and correlate more echocardiogram variables in this population. Rechallenging these patients with Carfilzomib, particularly during relapse stages, will remain a difficult decision especially if the therapy was effective. Disclosures Raza: Advisory board Incyte, Amgen, Celgene, Kite, Janseen, Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Moderna: Current equity holder in publicly-traded company; Drrx: Divested equity in a private or publicly-traded company in the past 24 months; Gilead, Sierra, Abbot, Acasti, Amicus: Current equity holder in private company; Received Honorarium/speaker bureu from Janseen, Celgene, Takeda: Ended employment in the past 24 months, Honoraria, Speakers Bureau.