Immune checkpoint inhibitor therapies and allogeneic hematopoietic cell transplant (alloHCT) represent two distinct modalities that offer a chance for long-term cure in a diverse array of ...malignancies and have experienced many breakthroughs in recent years. Herein, we review the CD27-CD70 co-stimulatory pathway and its therapeutic potential in 1) combination with checkpoint inhibitor and other immune therapies and 2) its potential ability to serve as a novel approach in graft-
-host disease (GVHD) prevention. We further review recent advances in the understanding of GVHD as a complex immune phenomenon between donor and host immune systems, particularly in the early stages with mixed chimerism, and potential novel therapeutic approaches to prevent the development of GVHD.
Aspirin is often stopped prior to percutaneous nephrolithotomy due to concern about the surgical bleeding risk. There is evidence that discontinuing aspirin perioperatively increases thromboembolic ...events and continuing it may be safe. We assessed the effect of continuing low dose aspirin through percutaneous nephrolithotomy and its effect on surgical and safety outcomes.
We retrospectively reviewed the records of 285 consecutive percutaneous nephrolithotomies performed between 2012 and 2015 at our institution. We compared outcomes and complications in patients who continued 81 mg aspirin daily to those in patients not receiving aspirin.
A total of 67 patients (24.5%) were maintained on low dose aspirin and 207 (75.5%) were not on aspirin. The aspirin group was older (66 vs 52 years), included more tobacco users (58.2% vs 31.4%) and had a higher ASA® (American Society of Anesthesiologists®) score (2.9 vs 2.5, all p <0.001). There was no difference in mean S.T.O.N.E. (size, topography stone location, obstruction, number of stones and evaluation of HU) score (7.6 vs 7.7, p = 0.71) or blood loss (44 vs 54 ml, p = 0.151). There was no difference in residual stone fragment size, including 0 to 2 mm in 65.3% vs 61.4% of aspirin vs no aspirin cases, 3 to 4 mm in 19.4% vs 16.2% and greater than 4 mm in 15.3% vs 22.4% (p = 0.407). Length of stay and the change in hemoglobin, hematocrit and creatinine were similar. There was no difference in the readmission rate (14.9% vs 12.6%, p = 0.618) or the total complication rate (34.4% vs 26.6%, p = 0.221). There was also no difference in the number of major complications (10.4% vs 5.8%, p = 0.193), bleeding complications (3.0% vs 2.9%, p = 0.971) and the transfusion rate (1.5% vs 1.0%, p = 0.57).
Percutaneous nephrolithotomy appears effective and safe in patients who continue low dose aspirin perioperatively.
We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).
We performed ...a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I
=65%) and 65.2% (95% CI 0.36-0.91, I
=57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I
=77%), 3.9% (95% CI 0.00-0.19, I
=22%), and 1.6% (95%CI 0.00-0.21, I
=33%), respectively.
CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
In light of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants potentially undermining humoral immunity, it is important to understand the fine specificity of the antiviral ...antibodies. We screened 20 COVID-19 patients for antibodies against 9 different SARS-CoV-2 proteins observing responses against the spike (S) proteins, the receptor-binding domain (RBD), and the nucleocapsid (N) protein which were of the IgG1 and IgG3 subtypes. Importantly, mutations which typically occur in the B.1.351 "South African" variant, significantly reduced the binding of anti-RBD antibodies. Nine of 20 patients were critically ill and were considered high-risk (HR). These patients showed significantly higher levels of transforming growth factor beta (TGF-β) and myeloid-derived suppressor cells (MDSC), and lower levels of CD4
T cells expressing LAG-3 compared to standard-risk (SR) patients. HR patients evidenced significantly higher anti-S1/RBD IgG antibody levels and an increased neutralizing activity. Importantly, a large proportion of S protein-specific antibodies were glycosylation-dependent and we identified a number of immunodominant linear epitopes within the S1 and N proteins. Findings derived from this study will not only help us to identify the most relevant component of the anti-SARS-CoV-2 humoral immune response but will also enable us to design more meaningful immunomonitoring methods for anti-COVID-19 vaccines.
Physicians recognize the importance of clinical documentation for accuracy of coding and billing, but it is emphasized little in residency curricula, with an even smaller emphasis on ...oncology-specific documentation. We developed an educational curriculum to teach residents about clinical documentation for cancer patients. Our tool kit includes didactics, simulated history and physical (H&P) documentation, and personal feedback.
A preintervention survey was first administered to gauge baseline knowledge. A simulated H&P was developed that required participants to complete their own assessment and plan. We delivered a 25-minute lecture regarding billing and coding along with documentation tips and tricks specific to hematology/oncology. Thereafter, we handed out a second H&P, and participants had to once again complete their own assessment and plan. These H&Ps were graded by three reviewers using a rubric. We then gave residents personalized feedback using the above data and administered a postintervention survey.
The postintervention survey revealed that 100% of the residents surveyed found this activity helpful, 83% noted that further knowledge of diagnosis codes was helpful to their learning, 100% noted that that this activity taught them to improve documentation, 91% said they were more likely to use cancer-specific diagnoses, and 91% said they would benefit from direct feedback-based education.
Didactic and formal education is more effective when combined with hands-on examples and direct personalized feedback.
Patients after autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) are at an increased risk of COVID-19-related morbidity and mortality, compounded by an immune system weakened by ...the underlying malignancy and prior treatments. Allogeneic transplantation, including stem cell and solid organ transplants, requires intensive immunosuppressive prophylaxis, which may further undermine the development of a protective vaccine-induced anti-viral immunity. Herein, we report on short- and long-term antiviral immune responses in two peri-stem cell transplant recipients and a third patient who received a COVID-19 vaccination after kidney transplantation. Our data indicate that: (1) patients post-alloSCT may be able to mount an anti-COVID-19 immune response; however, a sufficient time interval between transplant and exposure may be of critical importance; (2) alloSCT recipients with preexisting anti-SARS-CoV-2 immunity are at risk for losing protective humoral immunity following transplantation, particularly if the stem-cell donor lacks antiviral immunity, e.g., vaccine-derived immunity; and (3) some post-transplant patients are completely unable to build an immune response to a COVID-19 vaccine, perhaps based on the prophylactic suppression of T cell immunity.
A 51-year-old previously healthy woman presenting with two-weeks of fever, flu-like symptoms, jaundice, and abdominal pain was found to have pancytopenia, transaminitis, and significantly elevated ...ferritin in the setting of an Epstein-Barr Virus (EBV) infection. Bone marrow biopsy revealed phagocytic macrophages consistent with findings of hemophagocytic lymphohistiocytosis (HLH). Given bone marrow findings and that the patient had five of the eight clinical criteria supporting the diagnosis of HLH, chemotherapy was initiated as per the HLH-94 protocol with initial improvement in patient’s symptoms and overall functional status. This case demonstrates a classic presentation of HLH and displays the importance of correct diagnosis and prompt treatment.
Introduction:In recent years, many B-cell maturation antigen (BCMA) directed therapies (BDT) have demonstrated clinical response in heavily treated relapsed/refractory multiple myeloma (RRMM). These ...therapies include antibody-drug conjugates (ADC), chimeric antigen receptors (CAR-T), T-cell engaging bispecific antibodies (BsAb), and BCMA monoclonal antibodies (MoAb). BDT represents a breakthrough in the treatment of heavily treated RRMM. While these agents have led to deep responses and remissions, they have not been curative and many patients are exposed to more than one BDT. Optimal sequencing of BDT and outcomes in patients who received 2 or more BDT is not well understood. Our study aims to address these questions in this population. Methods: A retrospective review of 39 patients with RRMM that received 2 or more types of BDTs at the University of Kansas Medical Center, in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC), as of 7/10/2023 was completed. Responses to therapy including overall response rate (ORR), complete response or better (>CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. The Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS) assessments. OS was calculated from exposure of 1 st BDT till the last office visit/death. Regression models for univariate and multivariate analysis were performed. Results: Patients were previously treated with a median of 7 (4-12) prior lines of therapy before 2 nd BDT; 75% were Caucasians, 69% had IgG isotype, 74% had high-risk cytogenetics, and 51% had extramedullary disease (EMD). All patients were triple-class exposed, 95% were triple-class refractory, 82% were penta-class exposed and 74% were penta-class refractory, only 15% received 3 different types of BDTs. Median time between relapse after 1 st BDT to initiation of 2 nd BDT was 4 (0.5-33) months. Baseline characteristics are summarized in Table 1. Median follow-up was 19.4 (11.5-NR) months for the entire cohort. The most common first BDT were CAR-T and ADC (n=15, 38% and n=12, 31%), respectively. Whilethe most common second BDT were BsAb and CAR-T (n=17, 44% and n=13, 33%), respectively. The ORR after 1 st BDT and 2 nd BDT was 54% and 54%, respectively. The responses after 1 st BDT and 2 nd BDT were found to be deep (41% ≥VGPR, 36% ≥CR) and (44% ≥VGPR; 23% ≥CR), respectively. Detailed responses for the groups of interest are reported separately in Figure 1. The estimated median PFS for 1 st BDT was 5.8 months (95% CI 2.8-9.5) while for 2 nd BDT it was 5.2 months (95% CI 1.77-NA). Median OS from exposure to 1 st BDT was 19.5 months (95% CI 16.7-NA). At the time of data cut-off, 51% of patients had died with 90% of deaths were due to disease progression. Conclusions: This is one of the first reports on outcomes with second BDT in RRMM. Despite a heavily pre-treated patient population, 2 nd treatment with a BDT resulted in deep and durable responses, similar to treatment with 1 st BDT. Progression free survival was similar with 1 st and 2 nd BDT exposure. While our study is limited by a small population, our results support the use of a different type of BDT at progression even if previously exposed to a BCMA targeting agent. Further studies are needed to provide more guidance on appropriate sequencing of BDTs.
Background: The outcomes of patients with triple and penta-class relapsed refractory multiple myeloma (RRMM) are poor. B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-Cell ...(CAR-T) therapies in RRMM have been shown to improve outcomes since approval in 2021; however, relapses are common. We previously reported that patients lost BCMA expression after BCMA-directed therapy. Early re-emergence of surface BCMA on plasma cells (PC) in bone marrow (BM) may be a prognostic indicator for clinical relapse. Furthermore, there is limited published literature about clinical factors that increase risk of early BCMA re-emergence as well as clinical relapse post-CAR-T therapy. Methods: The study is a prospective cohort study that includes RRMM patients who underwent BCMA CAR-T at the University of Kansas Health System between May 2021 and May 2023 and were followed at regular intervals for the first-year post-infusion. All patients had standard procedure of BM evaluation at 1, 3, and 6 months, and 1 year. Eight-color MFC was performed on the BM specimens. BCMA antibody was purchased from R & D Systems (Minneapolis, MN). Data analysis was performed using FCS Express 5 software (De Novo Software, Los Angeles, CA). 500,000 to up to 2,000,000 events were acquired in all the cases. Responses were evaluated using the International Myeloma Working Group criteria. BCMA re-emergence was defined as BCMA greater than nadir on either polyclonal or monoclonal BM plasma cells. Results: 57 patients were evaluated and 44 patients (77 %) who lost their PC BCMA expression by multicolor flow cytometry (MFC) on bone marrow biopsy (BMBX) at Day 30 from baseline were included in the analysis. Demographic data of all 44 RRMM BCMA CAR-T recipients is shown Table 1. Median follow-up was 7 (4-14) months. Of the 44 patients, BCMA re-emergence was as follows: at 3-months (n=14, 32% of total sample), 6-months (n=5, 11%), 9-months (n=0, 0% of total sample), and 12-months (n=5, 11% of total sample). 14 (32%) of the 44 total patients had clinical relapse within 12 months. Of the 14 patients, 11 (79%) had BCMA re-emergence at any time point. 10 out of 11 (91%) of these patients had BCMA re-emergence before or at the same time as clinical relapse. The median time to BCMA re-emergence was 3 months and the median time to clinical relapse was 6 months. Only 1 patient had clinical relapse prior to BCMA re-emergence.Furthermore, at the 6-month mark, there were no significant clinical or demographic factors between those who relapsed vs. those who had a response to CAR-T therapy other than BCMA re-emergence (p-value 0.0445, Table 1). Conclusion: BCMA re-emergence on BM detected by MFC may be a prognostic indicator for clinical relapse in RRMM recipients of BCMA CAR-T therapies. It may be valuable to carry out close monitoring that includes evaluation of BCMA expression on BMBx at regular intervals post CAR-T therapy. Additional prospective studies with larger cohorts are needed to determine the risk factors for early BCMA re-emergence and clinical relapse in RRMM patients who receive BCMA CAR-T therapy.
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