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.

Immunophenotypic classification regarding prognosis in peripheral T cell lymphoma, NOS, and nodal T follicular helper T cell lymphoma, angioimmunoblastic-type.

This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.

Tixagevimab/cilgavimab (AZD7442/Evusheld) prevent from COVID19 in patients with hematologic malignancies under active chemotherapy.

Despite the efficacy of COVID-19 vaccines, patients with hematologic malignancy may still be fatal from COVID19. Therefore, we prospectively performed the analysis of administration of tixagevimab/cilgavimab in the real-world. In August 2022, 94 patients under active chemotherapy for lymphoma, multiple myeloma, or acute leukemia received a single dose AZD7442/Evusheld (two consecutive intramuscular injections of tixagevimab and cilgavimab, 300 mg each). Quantitative measurement of anti-SARS-CoV-2 spike protein (anti-S) and viral nucleocapsid (anti-N) titers were conducted before administration of tixagevimab/cilgavimab and at 1, 3, and 6 months after administration. Twenty-five patients (26.6%) had previously confirmed COVID-19 infection. Fifty-eight patients (61.7%) had previously received COVID-19 vaccinations, with a median of two doses (range, 1-5). The median anti-S Ab level increased from baseline (997.05 AU/mL) to 1 month (20,967.25 AU/mL), then decreased at 3 months (13,145.0 AU/mL), and 6 months (7123.0 AU/mL) (p < 0.001). There was no significant safety issue with tixagevimab/cilgavimab. With a median follow-up time of 6 months, thirteen patients (13.8%) had documented SARS-Cov-2 infection. A 20.2% rate of anti-N positivity was observed six months after the administration of tixagevimab/cilgavimab. The results of this study support the potential role of tixagevimab/cilgavimab for the prevention of symptomatic and severe COVID-19.Trial registration: KCT0007617; August 16, 2022.

Nation-Wide Retrospective Analysis of Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma: A Study from Korean Multiple Myeloma Working Party (KMM1913).

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response (sCR) plus CR rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3 and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0, 88.9, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion: AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea.

PURPOSE: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. MATERIALS AND METHODS: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. RESULTS: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. CONCLUSION: In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Catastrophizing Maladaptive Coping Affects the Association Between Viral Anxiety and Fear of Progression in Cancer Patients During COVID-19 Pandemic.

OBJECTIVE: The aim of the present study was to explore whether or not cancer patients' viral anxiety and depression during the coronavirus-2019 (COVID-19) pandemic were associated with a fear of cancer progression. We also assessed whether coping strategies affected the relationship. METHODS: The present cross-sectional survey included cancer patients who visited Ulsan University Hospital in Ulsan, Korea. The participants' demographic information and responses to the following symptoms rating scales were collected: Stress and Anxiety to Viral Epidemic-6; Patient Health Questionnaire-9; Cognitive Emotion Regulation Questionnaire-short version; or Fear of Progression Questionnaire-short version. RESULTS: Of the 558 cancer patients surveyed, 25 (4.5%) reported that their treatment schedule was delayed during the COVID-19 pandemic. The patients' fear of progression was found to be related to age (ß=-0.08; p=0.011), viral anxiety (ß=0.40; p<0.001), depression (ß=0.26; p<0.001), and catastrophizing coping strategies (ß=0.15; p=0.004), for an overall adjusted R2 of 0.46 (F=66.8; p<0.001). Mediation analysis showed that viral anxiety and depression were directly associated with fear of progression, while catastrophizing mediated this relationship. CONCLUSION: Fear of progression in cancer patients was associated with viral anxiety, depression, and maladaptive coping techniques, such as catastrophizing, during the COVID-19 pandemic.

A multi-center and non-interventional registry of brentuximab vedotin in patients with relapsed or refractory CD30-positive lymphoma: the CISL1803/BRAVO study.

Background: Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. In Korea, BV has been approved for the treatment of relapsed or refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL), and cutaneous T-cell lymphomas, including mycosis fungoides (MF). However, there are limited data reflecting real-world experiences with BV treatment for HL, ALCL, and MF. Methods: This was a multicenter, non-interventional registry study of the efficacy and safety of BV in patients with relapsed or refractory CD30-positive lymphoma (CISL1803/BRAVO). Outcomes were determined based on the occurrence of relapse or progression and overall survival after BV treatment. Results: A total of 85 patients were enrolled in this study. The median number of BV cycles was 10 (range, 2‒16) in the patients with HL. The objective response rate (ORR) of patients with HL to BV was 85.4% (41/48), comprising 27 complete responses (CRs) and 14 partial responses (PRs). The ORR of ALCL was 88% (22/25), consisting of 17 CRs and five PRs, whereas the ORR of MF was 92% (11/12). At the median follow-up of 44.6 months after BV treatment, the median post-BV progression-free survival of HL, ALCL, and MF patients was 23.6 months, 29.0 months, and 16.7 months, respectively (P=0.641). The most common side effect of BV was peripheral neuropathy; 22 patients (25.9%, 22/85) experienced peripheral neuropathy (all grades). Conclusion: The treatment outcomes of patients with relapsed or refractory CD30-positive lymphoma improved with BV treatment, and the safety profile was manageable.

Comparison of first-line treatment with CHOP versus ICED in patients with peripheral T-cell lymphoma eligible for upfront autologous stem cell transplantation.

Introduction: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods: We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results: Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion: In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.

LIGHT (TNFSF14) promotes the differentiation of human bone marrow-derived mesenchymal stem cells into functional hepatocyte-like cells.

Liver transplantation is the most effective treatment option for patients with acute or chronic liver failure. However, the applicability and effectiveness of this modality are often limited by a shortage of donors, surgical complications, high medical costs, and the need for continuing immunosuppressive therapy. An alternative approach is liver cell transplantation. LIGHT (a member of the tumor necrosis factor superfamily) could be a promising candidate for promoting the differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) into hepatocyte-like cells. In this study, we investigated the effect of LIGHT on hBM-MSC differentiation into hepatocyte-like cells. Our previous results showed that LIGHT receptor lymphotoxin-ß receptor (LTßR) is constitutively expressed on the surface of hBM-MSCs. Upon treatment with recombinant human LIGHT (rhLIGHT), the phenotype of hBM-MSCs changed to round or polygonal cells. In addition, the cells exhibited high levels of hepatocyte-specific markers, including albumin, cytokeratin-18 (CK-18), CK-19, cytochrome P450 family 1 subfamily A member 1 (CYP1A1), CYP1A2, CYP3A4, SRY-box transcription factor 17 (SOX17), and forkhead box A2 (FOXA2). These results indicate that rhLIGHT enhances the differentiation of hBM-MSCs into functional hepatocyte-like cells. Furthermore, rhLIGHT-induced hepatocyte-like cells showed a higher ability to store glycogen and uptake indocyanine green compared with control cells, indicating functional progression. Additionally, treatment with rhLIGHT increased the number, viability, and proliferation of cells by inducing the S/G2/M phase and upregulating the expression of various cyclin and cyclin dependent kinase (CDK) proteins. We also found that the hepatogenic differentiation of hBM-MSCs induced by rhLIGHT was mediated by the activation of signal transducer and activator of transcription 3 (STAT3) and STAT5 pathways. Overall, our findings suggest that LIGHT plays an essential role in promoting the hepatogenic differentiation of hBM-MSCs. Hence, LIGHT may be a valuable factor for stem cell therapy.

Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015).

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.

Risk factors of menopause after allogeneic hematopoietic cell transplantation in premenopausal adult women.

OBJECTIVES: Allogeneic hematopoietic stem-cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT. METHODS: We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT. RESULTS: The median age at HCT was 41.6 years (range, 22-53). Post-HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced-intensity conditioning (RIC) HCT (p = .101). In the multivariate analysis, the post-HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p = .016) and 9.3 times higher in RIC regimens containing 2-3 days of busulfan (p = .033) than that of non-busulfan-based conditioning regimens. CONCLUSIONS: Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post-HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

Real-world data of long-term survival in patients with T-cell lymphoma who underwent stem cell transplantation.

This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.

T-large granular lymphocytic leukemia.

T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway. Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

Plasmacytoid dendritic cell neoplasms.

Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN). MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

Performance Validation of Three Scoring Systems for the Prediction of Thrombotic Microangiopathy Due to Severe ADAMTS13 Deficiency and the Response to Therapeutic Plasma Exchange: First Study in Korea.

Background: The BENTLEY score (B-S), French thrombotic microangiopathy (TMA) Reference Center score (FTMA-S), and PLASMIC score (PLASMIC-S) have been developed for TMA diagnostic prediction. We retrospectively validated their predictive performances in patients with severe (<10%) disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in terms of the risk of TMA and response to therapeutic plasma exchange (TPE). Methods: The predictive performances of the three scoring systems were compared in 145 patients with suspected TMA who underwent ADAMTS13 activity tests between January 2014 and September 2022. The response to TPE and mortality in TMA-positive patients were compared after risk stratification, using the Mann-Whitney U and Fisher's exact tests. Results: The PLASMIC-S, FTMA-S, and B-S showed area under the curve values of 0.820, 0.636, and 0.513, respectively, for predicting TMA positivity in high-risk patients. The PLASMIC-S showed higher sensitivity (81.8%), negative predictive value (91.2%), positive predictive value (PPV; 66.7%), and accuracy (82.1%) than the FTMA-S (72.7%, 82.1%, 41.0%, and 60.0%, respectively) and B-S (4.6%, 70.2%, 50.0%, and 69.7%, respectively). The PLASMIC-S also showed higher specificity than the FTMA-S (82.2% vs. 54.5%). The modified PLASMIC-S, including lactate dehydrogenase/upper limit of normal ratios, increased the specificity, PPV, and accuracy to 97.0%, 92.3%, and 92.4%, respectively. In TMA-positive patients, high risk assessed by the PLASMIC-S predicted higher platelet recovery rates and less TPE sessions required for recovery than for those assessed at low-to-intermediate risk. Conclusions: PLASMIC-S is the preferred scoring system for detecting patients with TMA positivity and for prognosis before confirmation of ADAMTS13 activity.

Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122).

BACKGROUND: Current guidelines recommend using filgrastim or tbo-filgrastim to mobilize hematopoietic progenitor cells in an autologous setting. However, previous studies have suggested other forms of granulocyte colony-stimulating factor (G-CSF) are equally efficacious, possibly with fewer leukaphereses required. Thus, we prospectively studied the efficacy of lenograstim, a glycosylated recombinant form of G-CSF, in multiple myeloma (MM) patients. METHODS: From November 2011 to January 2020, 98 MM patients undergoing autologous stem cell transplant (ASCT) from five academic centers in Korea were enrolled. Patients were mobilized with subcutaneous lenograstim (Neutrogin®) with fixed doses of 10 µg/kg for 4 days. RESULTS: Most of the patients ( N  = 90, 91.8%) achieved at least the targets of 2 × 106 CD34+ cells/kg body weight, and more than half of MM patients ( N  = 57, 58.2%) reached a target of 5 × 106 CD34+ cells/kg body weight. The mobilization failure rate was 8.2% ( N  = 8). The median number of CD34 + cell/kg using G-CSF only was 5.25 × 106 /kg (range 0.49-13.47). Adverse events included transfusion (TF, N  = 53, 54.1%), bone pain ( N  = 6, 6.1%), fever ( N  = 2, 2.0%), and gastrointestinal troubles ( N  = 2, 2.0%). There were no grade 3 or 4 adverse events during mobilization. Body surface area (BSA) at mobilization and platelet TF were factors associated with CD34+ collection. Most patients achieved neutrophil ( N  = 93, 98.9%) and platelet ( N  = 89, 95.7%) engraftment. CONCLUSION: Lenograstim can safely and effectively mobilize stem cells in MM autologous settings.

A non-interventional, post-marketing surveillance study evaluating the safety and effectiveness of biosimilar rituximab (CT-P10) during routine clinical practice in the Republic of Korea.

BACKGROUND: CT-P10 was the first licensed rituximab biosimilar. This Korean post-marketing surveillance study evaluated CT-P10 safety and effectiveness in approved indications. RESEARCH DESIGN AND METHODS: This prospective, open-label, observational, phase 4 study collected routine clinical practice data across 27 centers in the Republic of Korea. Patients received their first CT-P10 treatment, per prescribing information, for non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) during the surveillance period (16 November 2016-15 November 2020). Safety (including adverse events [AEs] and adverse drug reactions [ADRs]) and disease-specific clinical response (by best overall response [NHL/CLL], Disease Activity Score in 28-joints [RA], or Birmingham Vasculitis Activity Score for Wegener's Granulomatosis [GPA/MPA]) were assessed for ≤1 year (NHL/CLL) or ≤24 weeks (RA/GPA/MPA). RESULTS: The safety population comprised 677 patients (604 NHL, 16 CLL, 42 RA, 7 GPA, 8 MPA). AEs/ADRs were reported for 68.4%/27.7% (NHL/CLL), 31.0%/14.3% (RA), and 86.7%/13.3% (GPA/MPA) of patients. Serious AEs and unexpected ADRs did not raise new safety signals. Pneumonia was the most frequent serious ADR overall. Positive effectiveness outcomes were observed. CONCLUSIONS: Findings were consistent with the known CT-P10/reference rituximab safety profile, with high effectiveness observed in NHL/CLL and RA.