Long-term efficacy and safety of tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: final analysis of phase IIb results.

Not available.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Trends in multiple myeloma incidence, prevalence, mortality, and survival rate in South Korea: a nationwide population-based study.

This is the first study presenting the overall descriptive epidemiology of multiple myeloma (MM), including incidence, mortality rate, and prevalence, in South Korea between 2010 and 2018 based on nationwide medical insurance coverage and mortality statistics data. The incidence of MM between 2010 and 2018 was obtained from nationwide medical claims data, and mortality data were obtained from the Korea National Statistical Office. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) and one- and five-year survival rates of patients with MM each year were estimated. There were 10,835 patients with MM aged ≥ 20 years in South Korea between 2010 and 2018. The ASIR was 2.42/100,000 in 2010 and increased to 2.71/100,000 in 2018, with an annual percent change (APC) of 1.86% (95% CI = 0.74-2.99%, P = 0.005). While this trend was significant in women, it was not statistically significant in men. The ASMR did not significantly change over time. Furthermore, the median survival time of patients with MM diagnosed between 2010 and 2018 was 3.36 years. Notably, the one-year survival rate of patients was increased from 65.3% in 2010 to 76.2% in 2017. Finally, the proportion of patients with MM who received novel therapeutic agents, such as proteasome inhibitors or immunomodulatory drugs, as first-line treatment increased from 37.7% in 2010 to 97.8% in 2018. The ASIR and prevalence of MM in South Korea increased between 2010 and 2018, especially in women and the survival rate of patients with MM has increased.

Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.

Real-world outcome of patients with extensively pretreated multiple myeloma who were treated with selinexor and dexamethasone: a Korean multicenter retrospective analysis.

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

Secondary Malignancies in Multiple Myeloma in Korean Patients: A Nationwide Population-Based Study.

PURPOSE: This study investigated the incidence of secondary malignancy in multiple myeloma (MM) patients compared with that in the general population using a population-based database covering all residents in Korea. MATERIALS AND METHODS: Based on the national health insurance system in Korea, all people primarily diagnosed with MM between January 1, 2010 to December 31, 2018 were identified. A total of 9,985 MM patients aged ≥ 20 years in Korea were included. RESULTS: Among them, 237 (2.4%) developed secondary malignancies by 2018. The standardized incidence rates (SIRs) of all secondary malignancies in MM patients were 0.87 (95% confidence interval [CI], 0.76 to 0.98), with a higher incidence of hematologic malignancies than in the general population with an SIR of 3.80 (95% CI, 2.61 to 5.00). The incidence rates of both lymphoid malignancy (SIR, 3.56; 95% CI, 2.31 to 4.82) and myeloid malignancy (SIR, 3.78; 95% CI, 1.16 to 6.39) were higher in MM patients than in the general population. In contrast, a lower incidence of solid cancer was observed in MM patients than in the general population (SIR, 0.76, 95% CI, 0.65 to 0.86). There was no significant difference in survival in MM patients without secondary malignancies, with hematologic malignancy, and with solid cancer (p=0.413). CONCLUSION: MM patients had a greater risk of secondary malignancies, especially hematologic malignancies, than the general population. Future studies with a focus on analyzing patients' history, treatment details, and genetic information in various stages of MM patients are needed to better understand the mechanism behind this increased risk.

4-1BB immunotherapy: advances and hurdles.

Since its initial description 35 years ago as an inducible molecule expressed in cytotoxic and helper T cells, 4-1BB has emerged as a crucial receptor in T-cell-mediated immune functions. Numerous studies have demonstrated the involvement of 4-1BB in infection and tumor immunity. However, the clinical development of 4-1BB agonist antibodies has been impeded by the occurrence of strong adverse events, notably hepatotoxicity, even though these antibodies have exhibited tremendous promise in in vivo tumor models. Efforts are currently underway to develop a new generation of agonist antibodies and recombinant proteins with modified effector functions that can harness the potent T-cell modulation properties of 4-1BB while mitigating adverse effects. In this review, we briefly examine the role of 4-1BB in T-cell biology, explore its clinical applications, and discuss future prospects in the field of 4-1BB agonist immunotherapy.

Outcomes of hematopoietic stem cell transplantation in patients with SARS-CoV-2 infection during the Omicron era.

Here, we present the outcomes of four patients with COVID-19 who underwent hematopoietic stem cell transplantation (HSCT) at the National Cancer Center in South Korea. Despite concerns of unfavorable course of COVID-19 in HSCT recipients, none of our patients experienced severe COVID-19. Moreover, extended viral shedding in Case 1, lasting over 100 days, resolved after successful engraftment. Contracting the virus when host could not mount an enough immune reaction might result in paradoxically favorable course. Vaccination, monoclonal antibodies, and antiviral agent usage against COVID-19 might also be effective. We suggest, if necessary, HSCT should not be deferred in COVID-19 patients.

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Patients and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen (44.8%) of the 29 patients achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.