A Caucasian man in his 60s with a medical history significant for ruptured left middle cerebral artery aneurysm status post clipping 2005 with residual right eye blindness and right leg weakness with gait instability presented with loss of balance, weakness of his legs and fatigue for 3 days. No other antecedent event was identified other than receiving Moderna COVID-19 vaccine 4 weeks before the presentation and 3 days before symptom onset. CT head and CT angiogram of the head and neck were performed and demonstrated no acute intracranial bleeding and no vascular abnormalities. With the findings of diffuse hyporeflexia and cerebrospinal fluid showing albumino-cytological dissociation, Guillain-Barré syndrome was high on the differentials. Electromyogram showed evidence of demyelination. He was treated with intravenous immune globulin (IVIG) and was discharged to rehab with complete symptom resolution.
Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium’s evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19–63%, and VGPR in 21–65%. The common adverse events were cytokine release syndrome (17–82%), anemia (5–52%), neutropenia (12–75%), and thrombocytopenia (14–42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.
e19530 Background: Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape. Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system. This study summarises the efficacy and safety of allogeneic CAR-T therapy in B cell malignancies. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, using MeSH terms and keywords for B cell malignancies and CAR-T therapy. We also screened the data presented in various conferences and handpicked references from previous systematic reviews. Outcomes of interest were complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS). Proportional outcomes were pooled using a random effects model (Freeman-Tukey double arcsine transformation) in OpenMetaAnalyst software. Results: The initial search retrieved 1247 articles. After excluding reviews, duplicates and non-relevant articles, we included data from 9 clinical trials (n = 146 patients). The most common malignancy was acute lymphoblastic leukemia (125 patients, 86%). The median age of patients ranged from 19 to 49 years. All patients received CD19 targeting therapy and the cell dose administered ranged from 0.4×10^6 to 5×10^8 cells/kg. CR was reported in 93 of 146 patients, with a pooled rate of 63% (95% CI 47.4 - 78.6%; I2 78.5%). The pooled 1-year OS was 57.3% (95% CI 30.8 - 82%; I2 79.2%). The pooled proportion of GVHD was 9.4% (95% CI 3.1- 15.6%; I2 47.6%). The pooled CRS and ICANS rates were 59.3% (95% CI 30.5 - 88.1%; I2 95.2%) and 15.4% (95% CI 4.6 - 26.3%; I2 72.7%), respectively. Conclusions: Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up.[Table: see text]
Neuroendocrine tumors usually originate from the neuroendocrine cells of gastrointestinal tract and their presence in the liver is mostly in the form of metastases. A primary neuroendocrine tumor in the liver concomitantly with hepatocellular carcinoma is an infrequent phenomenon. We present a 66-year-old woman with a remote history of breast cancer coming with postprandial fullness, later found to have multiple liver masses. After a thorough investigation, she was found to have a combined type of hepatocellular and primary neuroendocrine tumor of liver with pulmonary metastases. She was not a surgical candidate due to distant metastases. She was treated with chemotherapy, immunotherapy, and targeted therapies but continued to deteriorate clinically, and finally succumbed to her illness. The presence of this combined type of tumor in our patient is unique in many different ways: It is extremely rare, she did not have any risk factors for liver cancer, no genetic mutation till date could tie all these cancers (breast cancer, neuroendocrine tumor, and hepatocellular carcinoma) together, and not a lot of literatures/studies performed on this illness.
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