Anaplastic extramedullary plasmacytoma resistant to novel therapies: A case report

The treatment of choice for extramedullary plasmacytoma (EMP) is radiotherapy (RT). It is under discussion whether the management of an anaplastic form of EMP requires the addition of systemic therapy. We present a case of a 66-year-old male who was diagnosed with anaplastic plasmacytoma of the maxillary sinus. After the exclusion of multiple myeloma, Dara-VMP (daratumumab, bortezomib, melphalan, and prednisolone) regimen was initiated. During the third cycle of Dara-VMP, a progression of the tumor was observed. RT and BRd (bendamustine, dexamethasone, and lenalidomide) regimen were initiated. After 4 cycles of BRd, disease progression was established. KRd (carfilzomib, lenalidomide, and dexamethasone) regimen was initiated. The first cycle of KRd was not completed, as the patient was diagnosed with COVID-19. After the infection, the progression of EMP was observed. In this case, the anaplastic EMP was resistant to RT and chemotherapy regimens with novel agents, including a monoclonal antibody, an immunomodulatory drug, and proteasome inhibitors. Copyright © 2023 the author(s), published by De Gruyter, Berlin/Boston.

Outcomes of pregnant patients treated with REGEN-COV during the COVID-19 pandemic.

BACKGROUND: Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19-related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV. OBJECTIVE: This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics. STUDY DESIGN: This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19-positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection. RESULTS: From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath >24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups. CONCLUSION: Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19-related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics.

The decreasing effectiveness of conventional drugs due to multidrug-resistance is a major challenge for the scientific community, necessitating development of novel antimicrobial agents. In the present era of coronavirus 2 (COVID-19) pandemic, patients are being widely exposed to antimicrobial drugs and hence the problem of multidrug-resistance shall be aggravated in the days to come. Consequently, revisiting the phenomena of multidrug resistance leading to formulation of effective antimicrobial agents is the need of the hour. As a result, this review sheds light on the looming crisis of multidrug resistance in wake of the COVID-19 pandemic. It highlights the problem, significance and approaches for tackling microbial resistance with special emphasis on anti-microbial peptides as next-generation therapeutics against multidrug resistance associated diseases. Antimicrobial peptides exhibit exceptional mechanism of action enabling rapid killing of microbes at low concentration, antibiofilm activity, immunomodulatory properties along with a low tendency for resistance development providing them an edge over conventional antibiotics. The review is unique as it discusses the mode of action, pharmacodynamic properties and application of antimicrobial peptides in areas ranging from therapeutics to agriculture.

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond.

Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody-drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue on "Advances in the Treatment of Relapsed and Refractory Multiple Myeloma: Novel Agents, Immunotherapies and Beyond" summarizes the most recent registration trials and emerging immunotherapies in RRMM, gives an overview on latest insights on MM genomics and on tumor-induced changes within the MM microenvironment, and presents some of the most promising rationally derived future therapeutic strategies.

COVID-19: A Perspective from Clinical Neurology and Neuroscience.

Despite the increasing large population of COVID-19+ infected patients, knowledge of the disease remains limited. Understanding the effects and long-term implications of COVID-19 will be paramount to implementing the right public health measures and developing future preventive and effective treatments. In this article, we discuss currently available information with COVID-19-related neurological complications, possible routes of virus infection into the central nervous system, and hypothesis about virus-induced cytokine storm syndrome, long-term outcomes, as well as ongoing clinical studies of novel therapies and biomarkers for COVID-19. Understanding the effects of COVID-19 on neurological systems is crucial for properly diagnosing and caring for the disease. We need to be prepared that COVID-19 could cause long-lasting debilitations after the infection has cleared. Investigating long-term effects of the disease will yield insight for providing comprehensive care to the survivors. Understanding these risks will also lead to better treatments as well as inform policies to create a system capable of caring for those affected by COVID-19 long after the pandemic has subsided.