Efficacy and Safety of Daratumumab-based Regimens in Pretreated Light Chain (AL) Amyloidosis: A Systematic Review.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review.

Carfilzomib (CFZ) is a proteasome inhibitor currently approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Multiple trials are ongoing to evaluate its efficacy and safety in newly diagnosed multiple myeloma (NDMM). The use of CFZ-based two- or three-drug combination regimens as induction for the management of NDMM is an emerging approach. CFZ-based regimens include combinations of immunomodulators, alkylating agents, and monoclonal antibodies along with dexamethasone. In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response rates (ORR) ranging between 80% and 100%. Studies evaluating the combination of CFZ with daratumumab reported an ORR of approximately 100%. Achievement of minimal residual disease (MRD) negativity, measured by multi-parameter flow cytometry (MPFC), ranged between 60% and 95% in 4 (n=251) out of 6 studies that measured MRD-negativity. The interim results of the ENDURANCE trial failed to show superior efficacy and progression-free survival (PFS) of carfilzomib-lenalidomide when compared to bortezomib-lenalidomide combination, albeit with a lower incidence of neuropathy. Hematological toxicity was the most common adverse event observed with these regimens, and the most common non-hematological adverse events were related to cardiovascular and electrolyte disturbances. We need to further evaluate the role of CFZ in NDMM by conducting more Phase III trials with different combinations.

Advances in viral oncolytics for treatment of multiple myeloma - a focused review.

INTRODUCTION: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction. AREAS COVERED: This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM. EXPERT OPINION: Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue.

Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies.

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70-90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD.

Disseminated Hydatid Disease in a Child Involving Multiple Organ Systems: A Case Report.

Hydatid disease is a parasitic infestation by Echinococcus granulosus, which involves the liver and lungs primarily. The authors report a case of disseminated hydatid disease involving multiple organs simultaneously in a 7-year-old child from Kabul, Afghanistan. The patient under examination had been having a complaint of cough and low-grade fever for the last one year. Computed tomography (CT) and ultrasonography (USG) demonstrated cystic lesions in his liver, lungs, spleen, and suprarenal region. The literature review showed that it was very rare for hydatid disease to involve multiple organs simultaneously, even in endemic areas, and the management of disseminated disease was very challenging, especially in the pediatric population.

Report of a Fatal Case of Hemophagocytic Lymphohistiocytosis Syndrome and a Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in children, with a high mortality rate of 41.99%. Often, due to the atypical presentation of HLH, the syndrome is difficult to diagnose. We report a case of an atypical presentation of HLH and the diagnostic dilemma that we faced. An 11-year-old boy was hospitalized with recurrent fever, hepatosplenomegaly, and worsening jaundice. Initial laboratory workup revealed an elevated prothrombin time (PT), high bilirubin, increased alanine transaminase (ALT), and positive Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) and EBV immunoglobulin G (IgG). Based on our patient's presentation and initial laboratory findings, further extensive workup was done, which revealed cytopenias, hypofibrinogenemia, hemophagocytosis on biopsy, absent natural killer (NK) cell activity, high serum ferritin level, and high soluble CD25 (sIL-2 receptor); a diagnosis of HLH was made. He was started on broad-spectrum antibiotics, antivirals, antifungals, and cyclosporine. He became hypoxic and hypotensive and hence was intubated and started on vasopressors. However, his coagulation profile continued to deteriorate. He started bleeding from multiple sites and became unresponsive to ventilatory support, eventually dying as a result of complications of HLH. The ambiguous clinical presentation makes the diagnosis of this syndrome difficult. However, due to the high fatality rate, early recognition and prompt treatment are of utmost importance.