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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.
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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 plus complete response (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.
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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.
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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.
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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.
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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.
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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 (β=-0.08; p=0.011), viral anxiety (β=0.40; p<0.001), depression (β=0.26; p<0.001), and catastrophizing coping strategies (β=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.
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Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
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Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
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Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.
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Background@#Although survival outcomes of multiple myeloma (MM) have improved with the development of new and effective agents, infection remains the major cause of morbidity and mortality. Here, we evaluated the efficacy of levofloxacin prophylaxis (in a real-world setting) during bortezomib, melphalan, and prednisone (VMP) therapy in elderly patients with newly diagnosed MM. @*Methods@#This study retrospectively analyzed the records of patients with newly diagnosed MM treated with the VMP regimen between February 2011 and September 2020 at three institutes of the Republic of Korea. @*Results@#Of a total of 258 patients, 204 (79.1%) received levofloxacin prophylaxis during VMP therapy. The median number of levofloxacin prophylaxis cycles was 4 (range, 1‒9), but 10 patients did not complete the planned prophylaxis because of side effects. Sixty-six patients (25.5%) experienced severe infections during VMP therapy, most of which (74.7%) occurred within the first four cycles of VMP therapy regardless of levofloxacin prophylaxis status. Early severe infection was significantly associated with poor survival.In multivariate analysis, levofloxacin prophylaxis was significantly associated with a lower risk in early severe infection. @*Conclusion@#Our findings suggest that levofloxacin prophylaxis should be considered at least during the first four cycles of VMP therapy in elderly patients with newly diagnosed MM.
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Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
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Background/Aims@#For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. @*Methods@#This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. @*Results@#Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). @*Conclusions@#All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.
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Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.
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No abstract available.
Subject(s)
Bone Marrow , Diagnosis , Korea , Neoplasm Metastasis , Small Cell Lung Carcinoma , Tumor Lysis SyndromeABSTRACT
No abstract available.
Subject(s)
Bone Marrow , Lymphoma, Follicular , Lymphoma, Mantle-CellABSTRACT
The management of advanced prostate cancer has evolved rapidly. Androgen deprivation therapy, via surgical or medical castration, is the first-line therapy for hormone-naïve metastatic prostate cancer. For approximately a decade, docetaxel-based chemotherapy was the only approved agent to show a survival benefit for castration-resistant prostate cancer. However, over the last 5 years, significant advances in the field have led to the approval of several new agents with different mechanisms of action, such as the new androgen pathway inhibitors abiraterone and enzalutamide, a new cytotoxic agent, cabazitaxel, and new bone-seeking agents such as radium-223, which have all been associated with improved quality of life and pain palliation and an increase in survival. However, there has been no Korean treatment guideline for metastatic prostate cancer which is developed based on thorough search for relevant articles, including recently developed agents, and adequate review and assessment of evidences, and thus, a guideline adequate for domestic circumstance is eagerly needed. Experts from the Genitourinary Oncology Committee of the Korea Cancer Study Group developed clinical recommendations for the treatment of metastatic prostate cancer based on 19 key questions. The Korean Association for Clinical Oncology, the Korean Prostate Society, the Korean Urological Oncology Society, and the Korean Society of Pathologists reviewed and endorsed the guidelines. These are the first Korean treatment guidelines developed specifically for metastatic prostate cancer.
Subject(s)
Castration , Drug Therapy , Korea , Medical Oncology , Neoplasm Metastasis , Prostate , Prostatic Neoplasms , Quality of LifeABSTRACT
BACKGROUND: Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) is one of the effective chemotherapeutic regimens for patients with advanced stage marginal zone lymphoma (MZL). However, prognostic factors that affect the outcome of treatment for MZL are not well understood. METHODS: Between August 2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated with R-CVP as a first-line therapy from 15 institutions were retrospectively analyzed. Patients' clinical and laboratory data at diagnosis were collected by review of medical records. RESULTS: A total of 80 patients were analyzed. Bone marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue sites. Overall response rate was 91.3%, including 73.8% achieving complete response. Advanced MZL patients treated with R-CVP showed a 3-year progression-free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS in univariate analysis were platelet to lymphocyte ratio (PLR, 3.9 g/dL, P=0.008), and the International Prognostic Index (IPI) score (1 vs. 2–4, P=0.032). In multivariate analysis, only PLR (<95 vs. ≥95, HR 0.367, 95% CI, 0.139–0.971, P=0.043) was an independent risk factor for PFS. CONCLUSION: PLR ≥95 at diagnosis is an independent prognostic marker for PFS in advanced stage MZL patients treated with R-CVP. This marker may aid clinicians in predicting the response to R-CVP chemotherapy in stage III and IV MZL patients.
Subject(s)
Humans , Blood Platelets , Bone Marrow , Cyclophosphamide , Diagnosis , Disease-Free Survival , Drug Therapy , Drug Therapy, Combination , Lymphocytes , Lymphoma , Medical Records , Multivariate Analysis , Prednisone , Prognosis , Retrospective Studies , Risk Factors , Rituximab , Serum Albumin , VincristineABSTRACT
In Korea, scrub typhus usually occurs in October and November. Hemophagocytic lymphohistiocytosis (HLH) is a distinct clinical entity characterized by a high fever, pancytopenia, hepatosplenomegaly, histiocyte proliferation, and hemophagocytosis. We encountered a summertime case of severe scrub typhus presenting as HLH. A 49-year-old female complained of abdominal pain and fever 3 days in duration. On hospital day 3 she was transferred to the intensive care unit because of clinical deterioration accompanied by severe sepsis. As an eschar was evident on the right shoulder, we commenced doxycycline. Her condition improved dramatically and she was discharged on day 14. Although the indirect immunofluorescence antibody test (IFA) for Orientia tsutsugamushi was negative on admission, a repeat IFA test was positive; the antibody titer was 1:5,120 on hospital day 10. Scrub typhus should be considered during differential diagnosis in a patient with severe sepsis in any season except the fall.