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Background: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second‐line versus later‐line. Here, we present an updated pooled analysis with a longer follow‐up of 35.2 months. Methods: Data were pooled from two studies—BGB‐3111‐AU‐003 (NCT02343120) and BGB‐3111‐206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second‐line and the later‐line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. Results: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second‐line and 71 (63.4%) patients as later‐line therapy. After weighting, OS was significantly improved in the second‐line versus later‐line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second‐line versus later‐line group (27.8 vs. 22.1 months). ORR was numerically higher in the second‐line versus later‐line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. Conclusion: Zanubrutinib in second‐line treatment was associated with significantly improved OS compared with later‐line treatment of R/R MCL. This pooled analysis of two studies of zanubrutinib examined its efficacy and safety in the treatment of patients with recurrent/relapsed mantle cell lymphoma (MCL) in two different settings—second‐line and later‐line with long‐term follow‐up.This analysis showed that patients receiving zanubrutinib in the second‐line had significantly better overall survival than those who received it in the later‐line.The finding suggests that earlier use of zanubrutinib in the treatment line may lead to better outcomes in patients with recurrent/relapsed MCL. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is the standard treatment strategy for refractory or relapsed classical Hodgkin lymphoma (R/R cHL). However, a single transplantation is insufficient to cure the disease because of unfavorable risk factors. Herein, we evaluated the outcomes of single or tandem ASCT in patients with R/R cHL, especially in high‐risk patients. Methods: We retrospectively analyzed R/R cHL patients who underwent single or tandem ASCT between April 2000 and June 2021 at the Beijing Cancer Hospital and Peking University International Hospital. Results: A total of 134 patients were enrolled. Patients were allocated to a favorable‐risk group (group A, n = 33), an unfavorable‐risk group (group B, n = 81) that underwent single ASCT, and an unfavorable‐risk group that underwent tandem ASCT (group C, n = 20). The median follow‐up time was 99 months (range, 91–107 months), and no treatment‐related deaths occurred after single or tandem ASCT. However, 27 patients (2 in group C) died during the follow‐up period. The groups A, B, and C had 5‐year progression‐free survival (PFS) rates of 77.05%, 45%, and 74.67%, respectively (p = 0.0014), and 5‐year overall survival (OS) rates of 89.85%, 76.06%, and 95%, respectively (p = 0.18). Neither the median PFS rates of groups A and C nor the OS rates of all groups were reached. Conclusions: Our study discusses the advantages of tandem transplantation for high‐risk patients with R/R cHL. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, the different situations of identifying second primary malignant tumors (SPMTs) in lymphoma patients with synchronous solid tumors remain to be comprehensively investigated. Methods: We retrospectively collected information pertaining to lymphoma patients with synchronous solid tumors (diagnosed within 6 months) at Peking University Cancer Hospital & Institute between 2009 and 2019. The non‐parametric Aalen–Johansen estimator was applied to calculate cumulative incidence function in the competing risk model. Furthermore, propensity score‐matched analysis was performed to compare survival differences in lymphoma patients with or without synchronous solid tumors. Results: Thirty‐eight patients were enrolled. There were three situations of identifying SPMTs. First, in 15 patients (39.5%), SPMTs were identified before the initiation of any treatment. Among them, priority was given to anti‐lymphoma treatment in case of only three patients. Second, in 17 patients (44.7%), SPMTs were unexpectedly detected on surgical specimen assessment; of them, 13 received anti‐lymphoma treatment after surgery. Third, in six patients (15.8%), SPMTs were identified after the outset of treatment for the primary tumor; in this population, three of four patients with lymphoma switched toward the treatment plan for SPMTs. The 5‐year overall survival was 58.7%. The cumulative incidence function within 5 years was 26.6% for lymphoma and 14.7% for other solid tumors. The early identification of SPMTs was associated with better outcomes (p = 0.048). After balancing the baseline characteristics, no differences in survival were observed between lymphoma patients with and without synchronous solid tumors (p = 0.664). Conclusions: This is the first study to present the different situations of identifying SPMTs in lymphoma patients with synchronous solid tumors. In only <50% patients, SPMTs were identifiable at baseline. SPMT identification at different situations may make it difficult to choose the optimal therapeutic option, which may consequently impact patient survival. [ABSTRACT FROM AUTHOR]

Background: Despite numerous chimeric antigen receptor T‐cell (CAR‐T) trials conducted in China, no CAR‐T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR‐T manufacture abroad. Relma‐cel (JWCAR029), an anti‐CD19 product produced with a commercial‐ready process in China, was evaluated in the first prospective, single‐arm, multicenter, pivotal study of CAR‐T therapy conducted under Chinese IND to support an NMPA‐accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215). Methods: Patients were randomized to receive either 100 × 106 (low dose, n = 27) or 150 × 106 (high dose, n = 32) CAR+ T‐cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 daily × 3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3 months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics. Results: As of the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy‐evaluable patients, the primary endpoint of 3 month ORR was 60.3% (95% CI, 46.6–73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%. Conclusions: Relma‐cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR‐T‐associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China. [ABSTRACT FROM AUTHOR]

Background: The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods: A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results: The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P <.001). The 5‐year OS of patients with cHL, mature BCL, and PTCL changed from 55%, 49%, and 41% in 1996‐2000 to 79%, 65%, and 51% in 2011‐2015, respectively (P values were.014,.002, and.592, respectively). Conclusion: The survival of most types of lymphoma such as cHL and mature BCL, rather than PTCL, was improved significantly during the past two decades. [ABSTRACT FROM AUTHOR]

Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB‐DLBCL patients. We retrospectively reviewed data on 108 PB‐DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow‐up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5‐year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5‐year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10‐year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB‐DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB‐DLBCL patients. Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) has a continuous pattern of relapse, especially with frequent late relapses in the central nervous system (CNS) and contralateral breast. Rituximab and radiotherapy confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB‐DLBCL patients. [ABSTRACT FROM AUTHOR]

Aim The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. Methods GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China. The treatment period was 24 weeks; patients received obinutuzumab 1000 mg i.v. on Days (D)1, 8 and 15 of Cycle (C)1 (CLL patients: first infusion split over 2 days) and on D1 of C2-8 (all cycles: 21 days). PK parameters were estimated using non-compartmental analysis (NCA), and a population PK analysis was used to determine whether observed GERSHWIN PK data were in accordance with previous obinutuzumab PK studies in non-Chinese patients. Results The PK analysis population included 48 patients: 28 patients completed all treatment cycles. NCA showed a similar PK profile in Chinese patients with FL, DLBCL and CLL. Steady-state concentrations of obinutuzumab appeared to be reached at the start of C2 irrespective of histology. There was no apparent relationship between body weight and systemic exposure. Most PK profiles observed in GERSHWIN lay within the 90% prediction interval of simulated profiles. Conclusions Obinutuzumab exposure was comparable in CLL, DLBCL and FL patients. NCA and population PK analysis indicate that PK characteristics of Chinese patients with B-cell lymphomas are similar to those in non-Chinese patients. [ABSTRACT FROM AUTHOR]

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL., (© 2023 Wiley Periodicals LLC.)