Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical features associated with these complications, and how to prevent and treat them. We included four original studies for this focused review. All four agents (idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, belantamab mafodotin) have received FDA approval for adult RRMM patients. We went through the FDA access data packages of the approved agents to outline stepwise management of the complications for better patient outcomes.

Renal Cell Carcinoma Presenting With Combined Cervical Lymphadenopathy and Cardiac Metastasis Without Inferior Vena Cava Involvement.

Renal cell cancer is the third most common urological malignancy following prostate and bladder malignancies. Cardiac metastases to the right side of the heart without inferior vena cava (IVC) involvement are exceedingly rare, with only a handful of cases described in the literature. Metastasis to the head and neck region is also rare, occurring in an estimated 1% of cases. Here we present a case of a patient with recurrent syncopal events secondary to renal cell carcinoma without IVC involvement, with metastases both to the right ventricle and cervical lymph nodes. To our knowledge, this is the first case that presents with both of these rare findings together and that highlights cancer screening in patients with high risk factors and new exam findings in patients with syncopal events having negative initial workup.

Incidence and Management of Carfilzomib-induced Cardiovascular Toxicity; A Systematic Review and Meta-analysis.

BACKGROUND: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta- analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib. METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%. RESULTS: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and highgrade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively). CONCLUSION: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hypertension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib to recognize and treat baseline cardiovascular risk factors in such patients.

Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance.

A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Cardiac Surgery: Meta-Analysis and Systematic Review of the Literature.

The number of patients with severe aortic stenosis (AS) and a history of prior cardiac surgery has increased. Prior cardiac surgery increases the risk of adverse outcomes in patients undergoing aortic valve replacement. To evaluate the impact of prior cardiac surgery on clinical endpoints in patients undergoing transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR), we performed a literature search using PubMed, Embase, Google Scholar, and Scopus databases. The clinical endpoints included in our study were 30-day mortality, 1-2-year mortality, acute kidney injury (AKI), bleeding, stroke, procedural time, and duration of hospital stay. Seven studies, which included a total of 8221 patients, were selected. Our study found that TAVR was associated with a lower incidence of stroke and bleeding complications. There was no significant difference in terms of AKI, 30-day all-cause mortality, and 1-2-year all-cause mortality between the two groups. The average procedure time and duration of hospital stay were 170 min less (p ≤ 0.01) and 3.6 days shorter (p < 0.01) in patients with TAVR, respectively. In patients with prior coronary artery bypass graft and severe AS, both TAVR and SAVR are reasonable options. However, TAVR may be associated with a lower incidence of complications like stroke and perioperative bleeding, in addition to a shorter length of stay.

Usefulness of patient-reported outcomes to assess the effectiveness of topical hormonal therapy for gynecologic symptoms after antihormonal treatment for breast cancer.

The aim of this retrospective study was to assess the efficacy of topical hormonal therapy (THT) to relieve vaginal symptoms resulting from antihormonal therapy in women with hormone receptor-positive breast cancer. A total of 74 breast cancer patients who received THT for vaginal complaints were retrospectively identified and statistically matched with 74 control breast cancer patients with vaginal complaints with no documented use of THT. Symptom scores were recorded from the center's proprietary patient-reported outcomes database, Patient Care Monitor (ConcertoHealthAI, Boston). A baseline score was noted at the initiation of antihormonal therapy and was followed at 6 and 12 months. The median differences between baseline, 6-month, and 12-month scores were analyzed. Repeated measures analysis of variance assessed the impact of topical hormonal replacement. There was no statistically significant difference in score change between the two groups at 6 and 12 months. In the active THT group, there were no statistically significant differences in vaginal complaints or sexual problems over time: {F (2, 146) = 0.99, P = 0.369; and F (2, 146) = 1.56, P = 0.217}, respectively. In this study, the use of topical hormonal replacement was not effective in alleviating vaginal symptoms.

Recurrent Esophageal Stricture Secondary to Pemphigus Vulgaris: A Rare Diagnostic and Therapeutic Challenge.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of skin and mucous membranes, characterized by acantholysis, can be life threatening, and carries significant morbidity. Esophageal involvement is uncommon, and the diagnosis can often be delayed. Esophageal stricture secondary to PV is extremely rare, and there are no guidelines on the management of this complication. We present a case of recalcitrant esophageal stricture, secondary to PV, successfully treated with topical and intralesional steroids. Moreover, we review the literature pertaining to esophageal PV and the management of esophageal strictures.