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Potential synergism between Bruton’s tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142) Potential synergism between BTK inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab in patients with aggressive Relapsed/Refractory aggressive B-cell non-Hodgkin lymphoma.

Background/Aim: The combination of bendamustine and rituximab (BR) is highly effective in both treatment-naïve and relapsed or refractory mantle cell lymphoma (MCL). Due to the rarity of MCL and limited accessibility of BR, clinical outcome from BR in the routine clinical practice in Korean patients are limited. Patients and Methods: To evaluate the real-world outcomes of BR treatment for MCL in Korea, medical records from 37 patients were retrospectively analyzed. Results: Twenty-five patients received BR as first-line treatment, and ten, eight, and seven patients were classified as low-, intermediate-, and high-risk by MIPI-classification, respectively. With the follow-up duration of 24.3 months, the three-year progression-free survival (PFS) rate was 80.5%±11.8%. PFS significantly differed according to MIPI-classification (p=0.002) and TP53 status (p=0.042). The three-year overall survival (OS) rate was 92.0%±5.4%. In 12 patients who received BR as salvage treatment, the median age was 66. The median PFS was 12.8 months, and the three-year OS rate was 66.8%±16.2%. Conclusion: BR is an effective regimen for both newly-diagnosed and relapsed or refractory MCL patients in Korea, with favorable response rates and outcomes.

This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1–3 and 4–5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83–4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84–8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1–3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1–3 with high-intermediate/high IPI or Deauville scores 4–5 with low/low-intermediate IPI), and high-risk (Deauville scores 4–5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10–7.54] vs. 13.97 [95% CI 7.02–27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.

Background Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted. Methods We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes. Results B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival. Conclusions The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.

This observational study aimed to evaluate the prognostic significance of interim and final 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) responses to upfront autologous stem cell transplantation (ASCT) in patients with peripheral T cell lymphomas (PTCLs). A total of 118 patients, from two independent institutions, with newly diagnosed PTCLs were enrolled, and 96 of them were evaluated. PET/CT was assessed at diagnosis, and during and after the primary treatment. Clinical outcomes of interim and final PET/CT were compared between transplanted and non-transplanted patients. The responses of PET/CT were assessed based on visual analysis using the Deauville five-point scale (5-PS). Clinicopathological features of transplanted patients (n = 37) were similar to those of non-transplanted patients (n = 59). After a median follow-up of 60.8 months, only final PET/CT response based on 5-PS was the independent prognostic factor of survival outcome (P < 0.001; HR 8.215; 95% C.I. 2.97–22.72) in multivariate analysis. Interim PET/CT response did not have a differential potential for predicting progression-free survival (PFS). In 59 patients, with score 1 or 2 in final PET/CT, the PFS rate was not significantly different between transplanted and non-transplanted patients (P = 0.970). Moreover, among the 37 patients with final PET/CT response score of 3–4, the PFS rate was equally poor in both transplanted and non-transplanted patients (P = 0.178). Final PET/CT assessment, based on 5-PS, was an important prognostic parameter for primary treatment of PTCLs, regardless of upfront ASCT. Interim PET/CT response could not be an indicator to determine the requirement for upfront ASCT.

PurposeThe aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs.MethodsWe retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients.ResultsPosttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47–3.18) vs. 7.86 (5.66–10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20–4.41) vs. 4.42 (2.36–8.26) vs. 7.09 (3.57–14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort.ConclusionThe risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0–122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3–4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.