Publications by authors named "Ho-Jin Shin"

166 Publications

Safety, Pharmacokinetics and Pharmacodynamics of a Next-Generation Subcutaneously Administered Coagulation Factor IX Variant, Dalcinonacog Alfa, in Previously Treated Hemophilia B Patients.

J Thromb Haemost 2021 Feb 4. Epub 2021 Feb 4.

Catalyst Biosciences, South San Francisco, CA, USA.

Background: Dalcinonacog alfa (DalcA), a next-generation, recombinant human factor IX (FIX) variant was developed using a rational design approach for increased procoagulant activity and longer duration of action to be administered subcutaneously (SQ) for prophylaxis of hemophilia B bleeding episodes.

Objectives: To investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of DalcA.

Methods: This multicenter, Phase1/2a study (NCT03186677) was conducted in 11 males aged 12-65 years with severe hemophilia B. In cohort 1, subjects received intravenous (IV) 75 IU/kg BeneFIX® and DalcA. Cohorts 2 and 3 had DalcA IV 75 IU/kg and SQ 75 IU/kg or 150 IU/kg. Cohort 4 was omitted. Cohort 5 received daily SQ 150 IU/kg DalcA for 6 days and Cohort 6 received IV 75 IU/kg and daily SQ 150 IU/kg DalcA for 9 days. Blood sampling was performed for chemistry, hematology, PK, PD and anti-drug antibody (ADA) measurement. Subjects were monitored for safety endpoints for 30 days post-dosing.

Results: DalcA demonstrated a 24-fold greater potency over BeneFIX® and longer mean residence time (33.8 hours). SQ bioavailability 8.2-20.3%, beta half-life 53.9-106.9 hours and T 24-48 hours. A median 15.7% FIX activity level [IQR 14.9-16.6%] was reached after 6 daily doses. Neutralizing antibodies to ISU304, but not wt-FIX, occurred in 2 cousins.

Conclusions: The data demonstrated that DalcA achieved protective FIX activity levels between 11-18%, corresponding to a reduced chance of spontaneous bleeds. Based on the results, a Phase 2b trial to assess the safety and efficacy of 28 daily SQ doses of DalcA was performed.
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http://dx.doi.org/10.1111/jth.15259DOI Listing
February 2021

Clinical features and outcomes of hypocellular acute myeloid leukemia in adults: A Korean AML registry data.

Medicine (Baltimore) 2021 Jan;100(1):e24185

Department of Hematology, Leukemia Research Institute, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, South Korea.

Abstract: The hypocellular variant of acute myeloid leukemia (AML) is defined as bone marrow cellularity of <20% in a biopsy specimen at presentation. We performed a retrospective analysis of the clinical features and survival outcomes of hypocellular AML in a Korean population. We reviewed the medical records of all patients diagnosed with AML at nine hospitals participating in the Korean AML registry from 2006 to 2012. Overall survival (OS) and event-free survival (EFS) rates were calculated from the time of diagnosis until death or an event, respectively. In total, 2110 patients were enrolled and 102 (4.8%) were identified as having hypocellular AML. Patients with hypocellular AML were older than those with non-hypocellular AML (median age: 59 vs 49 years; P < .001) and presented with leukopenia more frequently (mean white blood cell count: 5810/μL vs 40549/μL; P < .001). There was no difference between patients with and without hypocellular AML in terms of the presence of antecedent hematologic disorders (5.9% vs 5.3%; P  = .809). FLT3-ITD and NPM1 mutations were less common in hypocellular than non-hypocellular AML (FLT3-ITD mutations: 1.2% vs 14.3%, P < .001; NPM1 mutations: 0% vs 9.5%, P = .019). No differences were seen between the hypocellular and non-hypocellular AML groups in the complete remission rate (53.9% vs 61.3%, P = .139) or early death rate (defined as any death before 8 weeks; 14.7% vs 13.0%, P = .629). The OS and EFS did not differ between the hypocellular and non-hypocellular AML groups (median OS: 16 vs 23 months, P = .169; median EFS: 6 vs 9 months, P = .215). Hypocellular AML is more frequently observed in older-aged patients and have fewer FLT3-ITD and NPM1 mutation, but the clinical outcomes of hypocellular AML do not differ from those of non-hypocellular AML.
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http://dx.doi.org/10.1097/MD.0000000000024185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793401PMC
January 2021

Prognostic Impact of Peripheral Blood T-Cell Subsets at the Time of Diagnosis on Survival in Patients with Diffuse Large B-Cell Lymphoma.

Acta Haematol 2020 Dec 3:1-11. Epub 2020 Dec 3.

Clinical Trial Center, Pusan National University Hospital, Busan, Republic of Korea.

Introduction: The effects of lymphocyte subtypes, including helper (Th), natural killer (NK), and regulatory (Treg) cells, and other T-cell subtypes on treatment outcomes in diffuse large B-cell lymphoma (DLBCL) patients are not clearly established.

Methods: Among 151 consecutive patients diagnosed with DLBCL, we collected peripheral blood samples at diagnosis from 91 patients who received at least 1 cycle of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) chemotherapy and analyzed lymphocyte subsets by flow cytometry.

Results: DLBCL patients had a higher proportion of CD4+CD25+ Treg (p < 0.001) and lower absolute lymphocyte count than those of healthy controls. Lymphopenia at diagnosis was associated with advanced-stage disease (p = 0.001), a high-intermediate/high-risk International Prognostic Index (IPI) (p < 0.001), and older age (p = 0.060). High-intermediate/high-risk IPI, high proportion of CD3+CD4+ Th cells, and extranodal site ≥2 correlated with unfavorable prognostic factors for survival. High proportion of Th cells was associated with fewer cytotoxic T cells and NK cells at the time of diagnosis.

Conclusion: This study showed an association between circulating lymphocyte subsets including Th cells, Tregs, and NK cells and clinical outcomes in DLBCL; however, further confirmation is needed via prospective trials.
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http://dx.doi.org/10.1159/000510912DOI Listing
December 2020

The impact of smartphone use on gait in young adults: Cognitive load vs posture of texting.

PLoS One 2020 12;15(10):e0240118. Epub 2020 Oct 12.

Department of Physical Therapy, Gachon University, Incheon, Republic of Korea.

Many researches have reported that the use of smartphones has a negative impact on gait variability and speed of pedestrians by dispersion of cognition, but the influence of factors other than cognitive function on gait is still unclear. The purpose of this study was to investigate the impact of smartphone use on spatiotemporal gait parameters in healthy young people while walking. 42 healthy young adults were recruited and instructed to walk in four conditions (walking without using a smartphone, typing on a smartphone with both hands, typing on a smartphone with one hand, and texting posture with non-task). All spatiotemporal gait parameters were measured using the GAITRite walkway. Compared to walking without using a smartphone, the subjects walked with a slower cadence and velocity and changed stride length and gait cycle and spent more time in contact with the ground when using a smartphone (p < 0.05). In addition, even if a texting posture was taken without performing a task, a similar change was observed when using a smartphone (p < 0.05). This study found that a cautious gait pattern occurred due to smartphone use, and that a change in gait appeared just by taking a posture without using smartphone.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240118PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549775PMC
December 2020

A Comparison of the Transient Effect of Complex and Core Stability Exercises on Static Balance Ability and Muscle Activation during Static Standing in Healthy Male Adults.

Healthcare (Basel) 2020 Oct 1;8(4). Epub 2020 Oct 1.

Department of Physical Therapy, Gachon University, Incheon 21936, Korea.

Balance ability is a necessary exercise factor required for the activities of daily living. This study investigated the effects of short-term complex exercise (CE) and core stability exercise (CSE) on balance ability and trunk and lower-extremity muscle activation on healthy male adults. Twenty-nine healthy male adults were included. All performed CE and CSE for 1 min each; the exercise order was randomized. The primary and secondary outcomes were balance ability and muscle activation, respectively. In balance ability, CE showed a significant difference in all variables in both eye-opened and eye-closed conditions compared with the baseline ( < 0.05). In comparisons among exercises, the path length and average velocity variables showed a significant decrease in the eye-opened condition, and the path length variable showed a significant decrease in the eye-closed condition ( < 0.05). In muscle activation, CE showed a significant increase in the gluteus medius (Gmed) and decrease in the rectus femoris (RF), tibialis anterior (TA), and RF/biceps femoris (BF) ratio in the eye-opened condition compared to the baseline and a significant decrease in RF and RF/BF ratio in the eye-closed condition ( < 0.05). Both CE and CSE improved the static balance ability. Furthermore, muscle activation significantly increases in Gmed and decreases in the RF, TA, and RF/BF ratio. Therefore, we recommend including CE in an exercise program that has the purpose of improving static balance ability.
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http://dx.doi.org/10.3390/healthcare8040375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711515PMC
October 2020

Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone.

Int J Hematol 2021 Jan 5;113(1):81-91. Epub 2020 Sep 5.

Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea.

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival.
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http://dx.doi.org/10.1007/s12185-020-02988-6DOI Listing
January 2021

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk.

J Hematol Oncol 2020 08 20;13(1):115. Epub 2020 Aug 20.

University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain.

Background: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM).

Methods: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk.

Results: After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR.

Conclusion: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status.

Trial Registration: ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.
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http://dx.doi.org/10.1186/s13045-020-00948-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439722PMC
August 2020

Thermotherapy Plus Neck Stabilization Exercise for Chronic Nonspecific Neck Pain in Elderly: A Single-Blinded Randomized Controlled Trial.

Int J Environ Res Public Health 2020 08 1;17(15). Epub 2020 Aug 1.

Department of Health Science, Gachon University Graduate School, Incheon 21936, Korea.

Neck pain is a serious problem for public health. This study aimed to compare the effects of thermotherapy plus neck stabilization exercise versus neck stabilization exercise alone on pain, neck disability, muscle properties, and alignment of the neck and shoulder in the elderly with chronic nonspecific neck pain. This study is a single-blinded randomized controlled trial. Thirty-five individuals with chronic nonspecific neck pain were randomly allocated to intervention ( = 18) or control ( = 17) groups. The intervention group received thermotherapy with a salt-pack for 30 min and performed a neck stabilization exercise for 40 min twice a day for 5 days (10 sessions). The control group performed a neck stabilization exercise at the same time points. Pain intensity, pain pressure threshold (PPT), neck disability index, muscle properties, and alignment of the neck and shoulder were evaluated before and after the intervention. Significant time and group interactions were observed for pain at rest ( < 0.001) and during movement ( < 0.001), and for PPT at the upper-trapezius ( < 0.001), levator-scapula ( = 0.003), and splenius-capitis ( = 0.001). The disability caused by neck pain also significantly changed between groups over time ( = 0.005). In comparison with the control group, the intervention group showed significant improvements in muscle properties for the upper-trapezius (tone, = 0.021; stiffness, = 0.017), levator-scapula (stiffness, = 0.025; elasticity, = 0.035), and splenius-capitis (stiffness, = 0.012), and alignment of the neck ( = 0.016) and shoulder ( < 0.001) over time. These results recommend the clinical use of salt pack thermotherapy in addition to neck stabilization exercise as a complementary intervention for chronic nonspecific neck pain control.
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http://dx.doi.org/10.3390/ijerph17155572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432917PMC
August 2020

Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era.

Sci Rep 2020 07 15;10(1):11649. Epub 2020 Jul 15.

Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2-3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1-2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1-2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071-4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.
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http://dx.doi.org/10.1038/s41598-020-68310-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363857PMC
July 2020

Manipulative Therapy Plus Ankle Therapeutic Exercises for Adolescent Baseball Players with Chronic Ankle Instability: A Single-Blinded Randomized Controlled Trial.

Int J Environ Res Public Health 2020 07 11;17(14). Epub 2020 Jul 11.

Graduate School of Integrative Medicine, CHA University, Seongnam 13488, Korea.

Manipulative therapies and exercises are commonly used for the management of chronic ankle instability (CAI), but there is no evidence regarding the efficacy of high-velocity low-amplitude manipulation (HVLA) in addition to ankle therapeutic exercise to improve CAI in adolescent baseball players (ABP). To compare the effects of HVLA plus ankle therapeutic exercise and ankle therapeutic exercise alone on ankle status, pain intensity, pain pressure threshold (PPT), range of motion (ROM) of the ankle joint, and balance ability in ABP with CAI, a single-blinded randomized controlled trial was conducted. A total of 31 ABP with CAI were randomly allocated to the intervention (n = 16) or control (n = 15) groups. The intervention group received HVLA plus resistance exercise twice a week for 4 weeks, while the control group received resistance exercise alone. Ankle status, pain intensity, PPT, ROM, and balance ability were assessed before and after the intervention. The American Orthopedic Foot and Ankle Society scores showed significant group and time interactions (total, = 0.002; pain, < 0.001; alignment, = 0.001). There were significant group and time interactions in pain intensity (resting pain, = 0.008; movement pain, < 0.001). For ROM, there were significant group and time interactions on dorsiflexion ( = 0.006) and eversion ( = 0.026). The unipedal stance of the balance ability showed significant group and time interactions in path length ( = 0.006) and velocity ( = 0.006). Adding HVLA to resistance exercises may be synergistically effective in improving the ankle status, pain intensity, ROM, and balance ability in ABP with CAI.
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http://dx.doi.org/10.3390/ijerph17144997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399978PMC
July 2020

Intravenous busulfan and melphalan versus high-dose melphalan as a conditioning regimen for early autologous stem cell transplantation in patients with multiple myeloma: a propensity score-matched analysis.

Leuk Lymphoma 2020 11 25;61(11):2714-2721. Epub 2020 Jun 25.

Seoul National University Hospital, Seoul, Republic of Korea.

We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months ( = 0.995). With respect to non-hematologic toxicities, infections were more frequently reported in the BUMEL group ( < 0.001). Three patients who received BUMEL developed veno-occlusive disease (VOD), and all of them recovered without administration of defibrotide. In conclusion, BUMEL is an effective alternative conditioning regimen in terms of efficacy, but attention should be paid to toxicities.
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http://dx.doi.org/10.1080/10428194.2020.1783448DOI Listing
November 2020

Autologous stem cell transplantation in elderly patients with multiple myeloma in Korea: the KMM1807 study.

Int J Hematol 2020 Jul 25;112(1):84-95. Epub 2020 May 25.

Center for Hematologic Malignancy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Geyonggi, 410-769, Republic of Korea.

Autologous stem cell transplantation (ASCT) is not frequently performed for elderly patients multiple myeloma (MM) in Korea, despite its being a standardized approach for young patients. Medical records of 150 patients from 15 Korean institutions who received ASCT at age ≥ 64 years were analyzed retrospectively. Patients included had symptomatic MM, and had received their first ASCT at age ≥ 64 following induction chemotherapy. The main outcome was the response after ASCT. Overall survival (OS) and progression-free survival (PFS) were also analyzed. Median time to ASCT was 6.3 months. Complete response plus stringent complete response rate increased from 36 (24.0%) to 105 (70.0%) after ASCT, and high-quality response (≥ very good partial response) increased from 96 (64.0%) to 125 (83.3%). With a median follow-up of 32.6 months after ASCT, 5-year OS and PFS were 59.7% and 22.8%, respectively. Febrile neutropenia occurred in 43.5%, and nausea (21.3%) and stomatitis (13.2%) were common grade 3-4 non-hematologic adverse events. Of 44 deaths, disease progression (n = 23) was the most common cause of mortality, followed by infection (n = 13). Treatment-related death occurred in four cases (2.7%). ASCT is an effective and safe option for elderly MM patients and is associated with superior clinical outcomes.
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http://dx.doi.org/10.1007/s12185-020-02869-yDOI Listing
July 2020

Mud Therapy Combined with Core Exercise for Chronic Nonspecific Low Back Pain: A Pilot, Single-Blind, Randomized Controlled Trial.

Evid Based Complement Alternat Med 2020 3;2020:7547452. Epub 2020 Apr 3.

Department of Physical Therapy, Gachon University, Incheon, Republic of Korea.

Background: Low back pain (LBP) is common in the elderly and an appropriate intervention for LBP management should be investigated. The aim of this study is to investigate the potential of mud-heat intervention combined with core exercise as an alternative intervention for relieving pain and improving motor function in individuals with nonspecific chronic LBP.

Methods: Thirty-one individuals with chronic nonspecific LBP were randomly allocated to either the intervention group ( = 16) or the control group ( = 15). The intervention group used a mud pack for 30 min and performed a core-exercise program for 50 min twice a day for 4 days (8 sessions). The control group performed the core-exercise program only, at the same time point as the intervention group. Pain intensity was assessed using a 100 mm visual analog scale and a pain pressure threshold (PPT) as the primary outcomes. The secondary outcome measures included functional disability by LBP (Oswestry Disability Index), muscle properties, and static/dynamic balance.

Results: There was a significant group difference in pain intensity at rest (=0.048) and in the PPT at the two sites assessed (2 cm lateral to L3 spinous process, =0.045; 2 cm lateral to L5 spinous process, =0.015). No group differences were found in terms of muscle properties. Compared to core exercise only, moor-heat therapy and core exercise showed a significant improvement in static balance (=0.026) and dynamic balance (=0.019).

Conclusion: Mud therapy combined with core exercise is effective in relieving pain and improving motor function in patients with chronic nonspecific LBP. Further research is needed to underpin these preliminary results.
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http://dx.doi.org/10.1155/2020/7547452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157804PMC
April 2020

Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study.

Leukemia 2021 01 16;35(1):62-74. Epub 2020 Mar 16.

Department of Haematology, The Alfred Hospital and Monash University, Melbourne, VIC, Australia.

Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6-3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27-7.95) months for combination therapy versus 7.26 (6.47-8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79-1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee's recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment.
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http://dx.doi.org/10.1038/s41375-020-0773-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787975PMC
January 2021

Phase II study of safety and efficacy of BEB (bendamustine, etoposide, and busulfan) conditioning regimen for autologous stem cell transplantation in non-Hodgkin lymphoma.

Ann Hematol 2020 Apr 5;99(4):819-828. Epub 2020 Feb 5.

Division of Hematology-Oncology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, South Korea.

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 10/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.
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http://dx.doi.org/10.1007/s00277-020-03942-6DOI Listing
April 2020

Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE).

Br J Haematol 2020 04 3;189(2):303-312. Epub 2020 Feb 3.

Seoul St. Mary's Hematology Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, South Korea.

In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice-daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once-daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months' follow-up, MMR was higher with radotinib 300 mg (86%) or 400 mg (83%) than with imatinib (75%). Among patients with BCR-ABL1 ≤ 10% at three months, MMR and molecular response 4·5 (MR ) were achieved within 48 months by more radotinib-treated patients (300 mg: 84% and 52%, respectively; 400 mg: 74% and 44%, respectively) than imatinib-treated patients (71% and 44%, respectively). Estimated overall and progression-free survival rates at 48 months were not significantly different between imatinib (94% and 94%, respectively) and radotinib 300 mg (99% and 97%, respectively) or 400 mg (95% and 93%, respectively). The treatment failure rate was significantly higher with imatinib (19%) than with radotinib 300 mg (6%; P = 0·0197) or 400 mg (5%; P = 0·0072). Safety profiles were consistent with previous reports; most adverse events occurred within 12 months. Radotinib continues to demonstrate robust, deep molecular responses, suggesting that treatment-free remission may be attainable.
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http://dx.doi.org/10.1111/bjh.16381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187446PMC
April 2020

Pomalidomide, cyclophosphamide, and dexamethasone for elderly patients with relapsed and refractory multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP-164 study).

Am J Hematol 2020 Jan 9. Epub 2020 Jan 9.

Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, South Korea.

Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality.
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http://dx.doi.org/10.1002/ajh.25726DOI Listing
January 2020

Clinical impacts of inflammatory markers and clinical factors in patients with relapsed or refractory diffuse large B-cell lymphoma.

Blood Res 2019 Dec 20;54(4):244-252. Epub 2019 Dec 20.

Department of Hematology, Dong-A University Hospital, Busan, Korea.

Background: Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL.

Methods: In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors.

Results: In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, =0.002; OS, HR=2.542, =0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, =0.002; OS, HR=2.621, =0.002), and high NCCN-IPI (PFS, HR=2.836, =0.003; OS, HR=2.928, =0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, <0.001; OS, <0.001).

Conclusion: In conclusion, dNLR, GPS, and NCCN-IPI appear to be excellent prognostic parameters for survival in relapsed/refractory DLBCL.
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http://dx.doi.org/10.5045/br.2019.54.4.244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942137PMC
December 2019

Poor prognostic impact of high serum ferritin levels in patients with a lower risk of diffuse large B cell lymphoma.

Int J Hematol 2020 Apr 6;111(4):559-566. Epub 2020 Jan 6.

Division of Hematology/Oncology, Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, 262 Gamcheon-ro, Seo-gu, Busan, 49267, South Korea.

The International Prognostic Index (IPI) and other prognostic models cannot accurately classify risks in patients with lower-risk diffuse large B cell lymphoma (DLBCL). This study retrospectively analyzed serum levels of ferritin (500 and ≥ 500 ng/mL) and other reported risk factors for survival in 312 patients. High and high-intermediate risk IPI scores (hazard ratio (HR) [95% confidence interval (CI)] 2.22 [1.33, 3.72], P = 0.002 and 2.29 [1.33, 3.93], P = 0.003, respectively) and ferritin concentration ≥ 500 ng/mL (HR [95% CI] 2.22 [1.37, 3.60], P = 0.001 and 2.18 [1.31, 3.63], P = 0.003, respectively) were independent poor prognostic factors for 5-year progression-free survival (PFS) and overall survival (OS) rates in all patients. Additionally, high ferritin level (≥ 500 ng/mL) was an independent poor prognostic factor for PFS and OS in patients with lower-risk IPI (HR [95% CI] 3.37 [1.36, 8.33], P = 0.009 and 3.29 [1.23, 8.83], P = 0.0018, respectively). In conclusion, serum ferritin levels may be helpful in predicting survival in patients with DLBCL, especially in those with lower-risk IPI scores.
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http://dx.doi.org/10.1007/s12185-019-02816-6DOI Listing
April 2020

Neutropenia following intravenous immunoglobulin therapy in adult patients with immune thrombocytopenic purpura: A single center experience and literature review.

Medicine (Baltimore) 2020 Jan;99(1):e18624

Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

The purpose of this study was to evaluate neutropenia following intravenous immunoglobulin (IVIG) therapy in adults with immune thrombocytopenic purpura (ITP).Our analysis included 88 patients with ITP, who received IVIG from January 2006 to March 2016, at Pusan National University Hospital in Korea. Their white blood cell (WBC) count and absolute neutrophil count (ANC) before and after IVIG treatment were analyzed.Of 88 patients, 24 patients (27.3%) were male, and 64 patients (72.7%) were female. Neutropenia developed in 8 patients (18.7%) after IVIG treatment. In patients with a decrease in WBC count and ANC compared to baseline, median WBC count decreased from 6280/μL to 4530/μL after IVIG therapy, and median ANC decreased from 3840/μL to 2840/μL after IVIG therapy. The neutropenia induced by IVIG had resolved spontaneously after several days, and the mean recovery time was 8.72 days after the completion of the IVIG treatment. During the neutropenic episodes, only one patient developed neutropenic fever, which subsided soon without any treatment.The results of this study suggest that IVIG may cause neutropenia commonly in adults with ITP, and it seems to be transient and self-limited. This study is meaningful as the first report that not only pediatric ITP patients may develop neutropenia post IVIG administration, but also adult patients suffering ITP.
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http://dx.doi.org/10.1097/MD.0000000000018624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946410PMC
January 2020

The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study).

Ann Hematol 2020 Feb 23;99(2):309-319. Epub 2019 Dec 23.

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea.

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.
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http://dx.doi.org/10.1007/s00277-019-03904-7DOI Listing
February 2020

Clinical features and treatment outcomes of limited-stage mantle cell lymphoma: Consortium for Improving Survival of Lymphoma report.

Ann Hematol 2020 Feb 18;99(2):223-228. Epub 2019 Dec 18.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.

Limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL) is an extremely rare disease. Thus, there is little data on the clinical features and treatment outcomes of patients with early-stage MCL. We examined consecutive stage I or II MCL 41 cases diagnosed between 2000 and 2016 in 16 institutions of the Consortium for Improving Survival of Lymphoma group. All cases were pathologically confirmed and systemic evaluation was performed for staging. The clinical features were reviewed, and the treatment outcomes were analyzed. The median age of patients was 66 years (range 19-85 years); there were more men (n = 31, 75.6%) than women. Most patients (n = 28, 68.3%) had stage 2 disease, and 29 (70.7%) were symptomatic. The elevation of lactate dehydrogenase (n = 2, 4.9%) was not common; thus, 39 patients (95.1%) had a low-risk score (0 or 1) for the International Prognostic Index, and 28 (68.3%) had a low-risk score (1-3) for the MCL International Prognostic Index. Most patients (n = 37, 90.1%) received chemotherapy as the first therapeutic strategy, while some received radiotherapy (n = 2), surgical resection (n = 1), or no treatment (n = 1). Of the patients who received chemotherapy, 23 (56.9%) received a rituximab-containing regimen, and R-CHOP (n = 17) and R-bendamustine (n = 5) were commonly used. The best response was noted in 97.4% (n = 38) of patients, including 32 who showed a complete response (78%). With a median follow-up duration of 40.6 months, the 42 months relapse-free survival was 59.1%, and the 5-year overall survival rate was 80.4%. Limited-state MCL showed indolent clinical and low-risk prognostic features. Chemotherapy could be effective for controlling localized MCL lesions, with high complete response rates.
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http://dx.doi.org/10.1007/s00277-019-03803-xDOI Listing
February 2020

Analysis of the Efficacy of Thalidomide Plus Dexamethasone-Based Regimens in Patients With Relapsed/Refractory Multiple Myeloma Who Received Prior Chemotherapy, Including Bortezomib and Lenalidomide: KMM-166 Study.

Clin Lymphoma Myeloma Leuk 2020 02 31;20(2):e97-e104. Epub 2019 Oct 31.

Division of Hematology-Oncology, Department of Internal Medicine, Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea. Electronic address:

Background: For patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM).

Patients And Methods: We conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide.

Results: In 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities.

Conclusion: Thalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.
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http://dx.doi.org/10.1016/j.clml.2019.10.017DOI Listing
February 2020

expression is a potential prognostic marker for patients with clear cell renal cell carcinoma.

Oncol Lett 2019 Dec 4;18(6):5731-5738. Epub 2019 Oct 4.

Department of Anatomy, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Novel biomarkers of ccRCC may provide crucial information on tumor features and prognosis. The present study aimed to determine whether the expression of γ-aminobutyric acid (GABA) A receptor subunit θ () could serve as a novel prognostic marker of ccRCC. GABA is the main inhibitory neurotransmitter in the brain that activates the receptor GABA, which is comprised of three subunit isoforms: GABRA3, GABRB3 and GABRQ. A recent study reported that GABRQ is involved in the initiation and progression of hepatocellular carcinoma; however, the role of GABRQ in ccRCC remains unknown. In the present study, clinical and transcriptomic data were obtained from cohorts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential expression levels among early (TI and II), late (TIII and IV), nonmetastatic (M0) and metastatic (M1, primary tumor) stages of ccRCC samples were then identified. Furthermore, the use of as a prognostic gene was analyzed using Uno's C-index based on the time-dependent area under the curve (AUC), the AUC of the receiver operating characteristic curve at 5 years, the Kaplan-Meier survival curve and multivariate analysis. The survival curve analysis revealed that low mRNA expression was significantly associated with a poor prognosis of ccRCC (P<0.001 and P=0.0012 for TCGA and ICGC data, respectively). In addition, analyses of the C-index and AUC values further supported this discriminatory power. Furthermore, the prognostic value of mRNA expression was confirmed by multivariate Cox regression analysis. Taken together, these results suggested that mRNA expression may be considered as a novel prognostic biomarker of ccRCC.
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http://dx.doi.org/10.3892/ol.2019.10960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865077PMC
December 2019

Subgroup analysis of a phase 2/3 study of rurioctocog alfa pegol in patients with severe hemophilia A: efficacy and safety in previously treated Korean patients.

Blood Res 2019 Sep 25;54(3):198-203. Epub 2019 Sep 25.

Baxalta US Inc., a Takeda Company, Cambridge, MA, USA.

Background: The efficacy and safety of extended half-life, full-length, pegylated recombinant factor VIII rurioctocog alfa pegol [BAX 855, ADYNOVATE (USA)/ADYNOVI (Europe); Baxalta US Inc., a Takeda company, Lexington, MA, USA] was investigated in previously treated Korean patients with severe hemophilia A (HA).

Methods: A post hoc data analysis from the international, multicenter, phase 2/3 PROLONG-ATE study of rurioctocog alfa pegol in patients with severe HA (NCT01736475) determined annualized bleeding rates (ABRs) and rates of adverse events (AEs) in Korean patients treated in this study.

Results: All 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-demand) completed the study [median (range) age, 28.0 (12-50) yr; weight, 64.8 (45-90) kg; 8 patients had ≥1 target joint at screening]. Median (range) ABR was 1.9 (0.0-14.5) for patients on prophylaxis and 62.2 for the patient receiving on-demand treatment. The hemostatic efficacy of rurioctocog alfa pegol was rated "excellent" or "good" and only single infusions were required per bleeding episode. ABRs improved in most patients compared with prestudy values. No dose adjustments were required for prophylaxis, and the dosing frequency was reduced in 8 patients, compared with their previous prophylaxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment.

Conclusion: This post hoc analysis of a small group of Korean patients with severe HA indicated that rurioctocog alfa pegol was effective, and no serious AEs were observed. For most patients, the dosing frequency was also reduced compared with their previous regimen.
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http://dx.doi.org/10.5045/br.2019.54.3.198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779944PMC
September 2019

Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma.

BMC Cancer 2019 Nov 10;19(1):1080. Epub 2019 Nov 10.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Background: The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib.

Methods: Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD).

Results: We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable.

Conclusions: Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification.

Trial Registration: The study population was patients who had relapsed or refractory HL or PMBCL, and patients were registered for our pilot study after providing written informed consent between November 2013 and November 2015 (CilinicalTrials.gov: NCT01965119).
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http://dx.doi.org/10.1186/s12885-019-6303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842512PMC
November 2019

BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results.

Haemophilia 2019 Nov 17;25(6):1011-1019. Epub 2019 Oct 17.

Bayer, Wuppertal, Germany.

Introduction: BAY 94-9027 is an extended-half-life, site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks.

Aim: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years.

Methods: Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension. Patients received on-demand treatment or prophylaxis (30-40 IU/kg twice weekly, 45-60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed.

Results: Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297-1965 days) and 223 (23-563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twice-weekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 44.5% were bleed-free during the last 6 months. No patients developed FVIII inhibitors.

Conclusions: BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years).
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http://dx.doi.org/10.1111/hae.13853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900134PMC
November 2019

Phase II study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study.

Cancer Commun (Lond) 2019 10 16;39(1):58. Epub 2019 Oct 16.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation.

Methods: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m), cyclophosphamide (750 mg/m), and vincristine (1.4 mg/m; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety.

Results: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%).

Conclusion: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.
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http://dx.doi.org/10.1186/s40880-019-0403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796378PMC
October 2019

Effect of Stem Cell Source and Dose on Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Idiopathic Aplastic Anemia: Data from the Korean Aplastic Anemia Trials.

Acta Haematol 2020 7;143(3):232-243. Epub 2019 Aug 7.

Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objective: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA).

Methods: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA.

Results: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors.

Conclusion: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.
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http://dx.doi.org/10.1159/000501496DOI Listing
August 2020

Benefits of additional cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy compared to four cycles of VTD for newly diagnosed multiple myeloma.

Bone Marrow Transplant 2019 12 29;54(12):2051-2059. Epub 2019 Jul 29.

Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n = 129 (67.9%); VTD6, n = 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P < 0.001), but, the pre- and post-ASCT ≥ very good partial response (VGPR), and 2-year PFS were similar. Multivariate analysis revealed age, β-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P = 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P = 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.
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http://dx.doi.org/10.1038/s41409-019-0629-7DOI Listing
December 2019