Rituximab-containing Regimens Research Articles

Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study

ObjectiveTo evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). MethodsThis retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. ResultsTwenty patients (8 females and 12 males; age range 1–26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3–8) versus 14 (5–25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2–101) and 22 (4–41) months, respectively. Two patients in conventional group died of disease progression and infection. ConclusionsRTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.

The impact of marginalization on diffuse large B-cell lymphoma overall survival: a retrospective cohort study

The aim of this study was to describe the impact of marginalization on DLBCL overall survival (OS) within the Canadian setting. We conducted a population-based retrospective cohort study of adult patients with newly diagnosed DLBCL in Ontario between 1 January 2005 and 31 December 2017 receiving a rituximab-containing chemotherapy regimen with curative intent followed until 1 March 2020. Our primary exposure of interest was the Ontario Marginalization Index (ON-Marg). The primary outcome was 2-year OS, accounting for patient age, sex, cancer characteristics, comorbidity burden, and rural dwelling status. While two-year overall survival was inferior for individuals in the most deprived marginalization quintile (70.4% Q5 vs. 76.0% Q1), after adjustment for relevant covariates neither the composite ON-Marg nor any of its dimensions had a significant effect. Within the Canadian context, among patients who receive chemotherapy, marginalization may not have a significant association with overall survival when accounting for key patient covariates, lending support for preserved outcomes.

Drug-induced pneumonitis risk in diffuse large B-cell/follicular lymphoma patients treated with R-CHOP-like regimen is associated with the use of granulocyte colony-stimulating growth factors.

Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.

Impact of debulking therapy on the clinical outcomes of axicabtagene ciloleucel in the treatment of relapsed or refractory large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2. Among the 50 patients in Cohort 5 who received axi-cel, 40% received ≥3 prior lines of chemotherapy, and 40% had disease that progressed while on the most recent chemotherapy. Forty-eight patients (96%) received debulking therapy, 14 (28%) radiotherapy only, and 34 (71%) systemic immunochemotherapy. Median decrease in tumor burden (per sum of product of diameters of target lesions) relative to screening was 17.4% with R-ICE/R-GDP, 4.3% with other debulking chemotherapies, and 6.3% with radiotherapy only. All patients were followed for ≥8 months. CRS was reported in 43 patients (86%), with 1 patient (2%) experiencing grade ≥3. NEs were reported in 28 patients (56%), with 6 (12%) experiencing grade ≥3. Cytopenias were the most frequent grade ≥3 adverse event (AE); 19 (38%) and 18 (36%) treated patients had any and grade ≥3 prolonged thrombocytopenia, respectively, and 25 (50%) and 24 (48%) patients had any and grade ≥3 prolonged neutropenia, respectively. Overall, patients who received debulking chemotherapy had higher incidences of serious treatment-emergent AEs than those who received radiotherapy only. At the 24-month analysis, objective response rate was 72%, and complete response rate was 56%. Median duration of response, progression-free survival, and overall survival were 25.8, 3.1, and 20.6 months, respectively. These results from exploratory Cohort 5 demonstrate the feasibility of debulking prior to axi-cel, and together with current real-world evidence, suggest that debulking regimens may help minimize the frequency and severity of CRS and NEs in patients with R/R LBCL. The incidence of other AEs observed in Cohort 5 suggest the risk/benefit profile was not improved via the debulking regimens studied here.

Safety and Efficacy Results from the Phase I Study of a Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory Mantle Cell Lymphoma

Background: Relapsed/Refractory (R/R) mantle cell Lymphoma (MCL) has poor long-term survival compared with other B-cell malignancies. As a result, there is an urgent need for safe and effective treatments, particularly for patients who have progressed on covalent (c) Bruton tyrosine kinase inhibitors (BTKis) therapy. LP-168 is a highly selective, next-generation BTKi with a unique dual binding mode: covalent binding to wild-type BTK and reversible binding to mutated BTK. Pre-clinical data has demonstrated that LP-168 is highly potent in inhibiting C481 mutated BTK. Here, we report the safety and efficacy of LP-168 monotherapy in the R/R MCL patients as part of an ongoing phase 1 study (NCT04993690) in B-cell malignancies. Methods: This is a Phase 1 first-in-human multicenter open-label study of LP-168 enrolling Chinese patients with B cell Non-Hodgkin Lymphoma (NHL) who have progressed after at least 1 or 2 prior treatments. The study has two parts: Phase 1a: “3+3” dose escalation and Phase 1b: dose expansion in disease-specific cohorts (e.g. R/R MCL, R/R MZL, etc.). Results: Between 10 August 2021 and 31 May 2023, 33 R/R MCL patients who received at least one dose were enrolled and received LP-168 100mg (n=8), 150mg (n=24), and 200mg (n=1) QD, respectively. Baseline characteristics are summarized in Table 1. The median age was 58 (range, 32-79) years old; 27 (81.8%) were male. 15 (45.5%) subjects had intermediate to high risk disease per MCL International Prognostic Index (MIPI). Median lines of prior therapies were 2 (range, 1-11) with 24.2% refractory to the last prior treatment. All patients have received rituximab or a rituximab-containing regimen. 19 (57.6%) subjects have received at least a cBTKi or cBTKi-containing regimen. The most common treatment emergent adverse events (TEAEs) (occurring in ≥20% subjects) were platelet count decreased (30.3%), neutropenia and anemia (27.3% each) and COVID-19 (24.2%), most of which were Grade 1. Grade 3 or more TEAEs were seen in 9 (27.3%) subjects. Serious AE (SAE) (lung infection, oral cavity infection and lymphocytosis, all Grade 3) occurred in 3 (9.1%) subjects. Dose interruptions due to AE occurred in 7 patients (21.2%)，but no AE has led to dose adjustment, drug discontinuation or death. Of 31 efficacy evaluable subjects with median follow up of 5.5 months (range: 2.0-22.5), 24 (77.4%) achieved response including 12 (38.7%) complete metabolic response or complete response (CMR/CR). In addition, 5 (71.4%) out of 7 subjects with blastoid/ pleomorphic variant MCL achieved response (2 CMR/CR, 3 PMR/PR). More importantly, of 17 subjects who had prior cBTKi exposure, 12 (70.6%) responded to LP-168 and 6 (35.3%) achieved CMR. LP-168 also showed efficacy in 2 subjects who have received ≥ 2 cBTKi treatments. Another 2 subjects responded to LP-168 even after disease progression on a cBTKi and a BTK degrader. 5 subjects have achieved progression-free survival (PFS) more than 1 year and are still on treatment (Figure 1). Conclusion: In this Phase 1 trial, the novel BTK inhibitor LP-168 demonstrated a high CR rate and durable response in heavily pre-treated R/R MCL including blastoid/pleomorphic variant with favorable safety. Moreover, LP-168 could effectively overcome the acquired resistance to prior cBTKi. Based on the safety, PK and preliminary efficacy data from the Phase 1 study so far, we have determined the recommended phase 2 dose (RP2D) for MCL as 150 mg QD. A phase 2 trial of LP-168 in R/R MCL is currently ongoing (NCT05716087).

Pembrolizumab with Rituximab in Relapsed/Refractory Follicular Lymphoma and Diffuse Large B Cell Lymphoma

Background: The tumor microenvironment (TME) plays a role in follicular lymphoma (FL) pathogenesis and survival. PD-1/PDL-1 inhibitors have been effective in non-Hodgkin lymphoma subtypes, such as primary mediastinal B-cell lymphoma, and pembrolizumab + rituximab (P-R) produced a complete response (CR) in 50% of patients with rituximab-sensitive, relapsed/refractory (R/R) FL (Nastoupil ASH 2017, Blood Adv 2022). In 2018, we conducted a phase 2 study to assess the efficacy and safety of P-R in R/R FL and diffuse large B cell lymphoma (DLBCL) including rituximab-resistant patients. Methods: This phase 2, single-center, open-label, non-randomized trial aimed to determine the objective response rate (ORR) of P-R in R/R FL (Arm A) and R/R DLBCL (Arm B). A 3 rd arm with P + Obinutuzumab (O) for R/R FL was added later (Arm C). Eligible patients had R/R disease; for FL, patients must have received prior anti-CD20 therapy and have an indication for treatment; for DLBCL, patients must have relapsed after or be ineligible for autologous stem cell transplantation. Arm A sought to include > 9 patients with rituximab-refractory disease. Weekly R 375 mg/m2 x 4 and 4 doses of P (200 mg in q21 day cycles) were given as induction; responders could receive extended P monotherapy for up to 2 years. In Arm C, patients received weekly O x 4; those with at least SD and clinical benefit could receive P for up to 2 years and 6 more doses of O given every 3 months. CT was used for on-treatment tumor assessments after cycles 4 and 8, then every 12 weeks. A 2-stage design required response at cycle 4 among at least 3 of the first 7 patients in Arm A, and among 3 of the first 9 patients in Arm B, to permit accrual to 20 (Arm A) and 17 patients (Arm B). In Arm C, at least 6 responses in the first 12 patients would be needed to proceed to total accrual of 25 patients. Additional stopping rules were included for excess deaths (>10%) and serious adverse events (SAEs) (>50%). Results: Between 4/2018 and 11/2021, 18 patients were treated on study (Table 1). All were previously treated with rituximab, with 9 refractory to their last rituximab-containing regimen. Median age was 56, 78, and 45 and median prior lines of therapy was 4, 3, and 2 in Arms A, B, and C respectively. In Arm A, 2/7 patients had rituximab-refractory disease, and int- or high-risk FLIPI. All patients in Arm B were refractory to their most recent line of therapy, and 75% had IPI > 3. In Arm A, ORR was 29% (1 CR, 1 PR). In Arm B, no patients responded (6 PD, 1 SD, 1 unevaluable). In Arm C, 3 were accrued and achieved SD as best response. Figure 1 shows outcomes of all accrued patients. Treatment-related adverse events (AE) occurred in 83% of patients, with 9 grade 3/4 AEs occurring in 5 (28%) patients (1 acute kidney injury, 2 diarrhea, 1 hypokalemia, 1 arthralgia, 1 infusion reaction, 1 back pain, 1 generalized muscle weakness, 1 heart failure). There were 5 possible grade 3/4 immune-related AEs, including 2 suspected colitis treated with steroids. With a median follow up of 4.2 years, there were 8 deaths, 6 from progressive lymphoma, 1 from AML likely related to prior therapy, and 1 from a combination of progressive lymphoma and therapy-related AML. Arms A and B closed due to futility, having failed to exceed minimum efficacy for further accrual. Arm C was closed after demonstration of no responses and discussion with the study sponsor following accrual of 3 patients. Conclusion: P-R has modest, expected toxicity but low efficacy in R/R FL and DLBCL patients previously treated with R. Our data align with CHECKMATE-140 in FL (4% ORR, Armand Blood 2021) and data from post-transplant DLBCL (10% ORR post-ASCT, Ansell JCO 2019). Despite similarities in age and FLIPI distribution with data from Nastoupil et al, we failed to confirm those efficacy findings, a finding partly attributable to inclusion of rituximab-resistant patients. Our data suggest limited utility of combined anti-CD20 and anti-PD-1 therapy in R/R FL and DLBCL, and support exploration of alternative strategies to target the TME in these diseases.

A Novel Nomogram Predicting Rituximab-Associated Interstitial Pneumonia in Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Analysis of Single-Center

Background: The incidence rate of rituximab-induced interstitial lung disease (RILD) was reported to be 3.7%-16.7%. The onset of RILD was insidious, and the clinical symptoms were atypical. The course of the RILD progressed rapidly without timely treatment. However, there were no models reported to predict the risk of RILD. Herein, we investigated the incidence of RILD in consecutive patients with diffuse large B-cell lymphoma (DLBCL) and its correlation with clinicopathological features, and a novel nomogram was constructed to successfully predict the risk of RILD. Methods: The clinicopathological data of 110 consecutive patients with DLBCL who were treated in the Department of Hematology of Beijing Tongren Hospital from January 2020 to December 2022 were retrospectively collected, and all patients received first-line treatment regimens containing rituximab. The occurrence of interstitial pneumonia was assessed by chest CT or interim PET-CT. Efficacy was assessed according to Lugano criteria, and chi-square test was used to assess the difference in RILD in different characteristic groups. Results: The complete remission rate of 110 patients with DLBCL after treatment was 84.2%. Twenty-one patients (19.1%) developed RILD during treatment, and the median time of occurrence was the 4th cycle（range: 2~8). The median duration of treatment for RILD was 10 days (range: 5~60). Except for 5 patients with no obvious symptoms, all 16 patients received glucocorticoid-containing regimens, and all patients improved after treatment. The incidence of RILD was significantly higher in patients who received liposomal doxorubicin-containing regimens than those treated with adriamycin regimens (29.7% versus 13.7%, P=0.043). Smoking ( P=0.298) and advanced age ( P=0.156) were associated with a high incidence of RILD. Then we developed a RILD risk prediction model according to the risk factors, and the patients were divided into high-risk and low-risk groups, and the incidence of RILD was significantly different between the two groups ( P=0.027). Finally, a novel nomogram related to the occurrence of RILD in DLBCL patients was developed to scientifically and accurately predict the incidence of RILD. Conclusion: Patients with DLBCL should be alert to the occurrence of RILD after chemotherapy with rituximab-containing regimen, especially in smoking and elderly patients, and the prevention and monitoring of RILD should be strengthened after the application of liposomal doxorubicin.

Clinical Characteristics, Treatment Trends, and Outcomes of Patients with HHV-8-Negative/Idiopathic Multicentric Castleman Disease Treated with Siltuximab in a Machine Learning-Selected Real-World Cohort

Background HHV-8-negative/Idiopathic Multicentric Castleman Disease (iMCD) is a rare lymphoproliferative disorder with limited treatment options and poor outcomes. Siltuximab remains the only FDA approved treatment for the disease (April 2014), but its uptake and associated outcomes outside of clinical trials remain unclear. Further, constructing a large enough cohort of patients with iMCD to better understand siltuximab use in real-world practice is a challenge due to its low incidence, lack of a Castleman Disease (CD)-specific ICD code until 2017, and effort required for manual chart abstraction. We built a natural language processing-based machine learning (ML) model to select patients with iMCD from a nationwide electronic health record (EHR)-derived database and described their clinical characteristics, treatment trends, and real-world overall survival (rwOS). Methods Across a cohort of over 3.5 million patients in the EHR-derived, Flatiron Health database (which comprises de-identified patient-level structured and unstructured data from ~280 US cancer clinics and ~800 sites of care), patients with ML-extracted diagnoses and dates of diagnoses for iMCD and a visit on or after 2011 were selected. Precision (positive predictive value) of the ML-selected cohort was measured on 50 human abstracted charts. Descriptive statistics summarized patient characteristics and treatment trends. Treatment patterns were assessed among patients diagnosed on or before January 31, 2023 to allow a minimum of 3 months for treatment initiation. Changes over time in first-line (1L) treatment status were measured by diagnosis year category (<2014, 2014-2018, 2019-2023), and were chosen based on siltuximab approval date (2014) and publication of treatment guidelines for iMCD (2018). 1L regimens were grouped into one of the following mutually exclusive categories in hierarchical order: siltuximab-containing regimen, rituximab-containing regimen, and primary chemotherapy-containing regimen. 5-year rwOS rates for the entire iMCD cohort (indexed to diagnosis date), as well as patients with 1L-siltuximab or non-siltuximab regimens (indexed to treatment start date) were estimated using the Kaplan-Meier estimator. Patients with a diagnosis date before 2011 were excluded from survival analyses to avoid immortal time bias. Results The ML model selected 267 patients as having iMCD across the Flatiron network. The precision of the model was 90% for a CD diagnosis (including unicentric, HHV-8-associated multicentric, or unclassified CD) and 76% for the iMCD cohort. Patients with iMCD were predominantly male (55%), white (53%), and had a median age at diagnosis of 52. Compared to patients treated with non-siltuximab 1L therapy (N=122), patients treated with siltuximab-based regimens in 1L (N=67) were more likely to have been diagnosed more recently, seen in the community setting, and have a documented ECOG performance status (p<0.05) but were otherwise similar (Table 1). Among patients with evidence of treatment, use of 1L siltuximab-based regimens increased from 35% of patients diagnosed 2014-2018 to 46% diagnosed 2019-2023 while 1L rituximab-based regimen use dropped from 46% to 35%. 1L primary chemotherapy-based regimen use dropped from 41% prior to 2014 to 19% post 2014 (Figure 1). Among patients diagnosed after 2014 and who had evidence of treatment, 51% (77/151) received siltuximab at any point. Unadjusted 5-year rwOS rate for the entire iMCD cohort, including patients without evidence of treatment, was 84% [95% CI: 78-90%]. For patients treated with a 1L siltuximab-containing regimen, unadjusted 5-year rwOS was 86% [95% CI: 78%-96%], whereas for patients treated with non-siltuximab based 1L therapy, unadjusted 5-year rwOS was 81% [95% CI: 72%-90%]. Conclusion ML extraction allowed for the largest analysis of real-world patients with iMCD to date. While use of siltuximab in the 1L setting is increasing over time, only half of patients with evidence of treatment receive it at any point. Unadjusted 5-year rwOS rates for those treated with both siltuximab and non-siltuximab based 1L therapy was higher than previously reported. This may be due to the inclusion of other CD subtypes in the cohort or sicker patients not being seen in an outpatient oncology setting. Future work should explore the drivers of poor outcomes for patients as well as the factors associated with lack of receipt of siltuximab.

Baseline 18f-Fluorodeoxyglucose PET/CT Radiomics Predicts Outcome in Newly Diagnosed Intravascular Large B-Cell Lymphoma

[Introduction] Treatment outcomes of intravascular large B-cell lymphoma (IVLBCL), a rare subtype of extra-nodal diffuse large B-cell lymphoma (DLBCL), have dramatically improved in recent years. However, prognostic factors for IVLBCL are largely unknown. Several studies have explored the potential of the baseline 18F-fluorodeoxyglucose (FDG) PET/CT radiomics features to identify patients with poor prognosis. For example, metabolic tumor volume (MTV) reflects the FDG-avid tumor burden, and the maximum distance between the largest lesion and any other lesion quantifies the dissemination of the tumor, and both factors are inversely related to overall survival (OS) and progression-survival (PFS) in DLBCL. In this study, we explored prognostic impact of FDG PET/CT radiomics features in newly diagnosed IVLBCL. [Methods] We retrospectively evaluated patients with histopathologically proven newly diagnosed IVLBCL according to the 2008 World Health Organization criteria between January 2010 through February 2022 from hospitals participating in the North Japan Hematology Study Group (NJHSG). Quantitative analysis of all FDG PET/CT was performed using Metavol (Hokkaido University, Sapporo, Japan), with exclusion of physiological accumulation. MTV was defined as the volume of lymphoma lesions visualized on PET/CT scans with standardized uptake value (SUV) peaks greater than or equal to hepatic SUV peak. To quantify the dissemination of the tumor, we calculated the number of the body areas (head-neck, chest, abdomen, upper-extremities, lower-extremities) having BM lesions with a higher SUV peak than liver SUV peak. Patients with BM lesions spread across 4-5 areas were defined as cases having widely disseminated lesions (WDL). Progression-free survival (PFS) was defined as the time from the start of treatment to the first of progression, relapse, or death from any cause. Patients undergoing upfront autologous stem-cell transplantation (auto-SCT) were censored at the time of transplantation. [Results] We identified fifty-two IVLBCL patients (age 30-89 years, median 65 years; 57.7% male) who performed FDG PET/CT at diagnosis. Twenty-eight patients (54.9%) had poor performance status (ECOG PS ≥2), and 49 patients (94.2%) showed stage III-IV. Forty-nine patients (94.2%) had 2 or more extranodal involvement. Elevated serum LDH level was observed in 49 cases (94.2%) (median, 623.5 IU/L; range, 147-4907 IU/L). The median serum levels of soluble IL-2 receptor (sIL-2R), ferritin, and C-reactive protein (CRP) were 4496.5 IU/mL (range, 321-19900 IU/mL), 655.15 ng/mL (range, 50-6657 ng/mL), and 6.905 mg/dL (range, 0.11-25.86 mg/dL), respectively. The median MTV was 415.527 cm 3 (range, 0-3000 cm 3). ROC analysis revealed that the cutoff value of the MTV > 388 cm 3 could predict progression events within 2 years. Area under curve was 0.71 (95% CI: 0.564-0.857). Twenty-nine patients (55.8%) were classified as having MTV > 388 cm 3 (high MTV). Twenty-three patients (44.2%) had WDL. Fifty-one (98.1%) patients received chemotherapy, all of which was rituximab-containing regimen. Three patients (5.8%) received upfront auto-SCT. Median follow-up duration was 48.8 months (range, 5.8-140.5 months) in survivors. Age, LDH level, number of extranodal lesions, clinical stage, and PS did not affect OS and PFS. Although the high MTV and WDL did not significantly affect OS ( P = 0.095, P = 0.173, respectively; Log-rank), these findings did correlate significantly with poor PFS ( P = 0.011, P = 0.042, respectively; Log-rank). Thus, we defined a high MTV or a WDL as poor PET findings. Thirty-two patients had poor PET findings. Importantly, patients with poor PET findings showed significantly poor OS and PFS compared to patients without (2-year OS: 71.2% vs. 93.3%, P = 0.015, 2-year PFS: 45.5% vs. 93.8%, P = 0.001; Log-rank, Fig. 1, 2). [Conclusion] This is the largest study to assess prognostic impact of FDG PET/CT radiomics features on newly diagnosed IVLBCL. Poor PET findings were significantly correlated with worse OS and PFS.

Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study.

Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20mg once daily for 8weeks, followed by 20mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.

RITUXIMAB‐CONTAINING COMBINED MODALITY THERAPY IN LIMITED STAGE FOLLICULAR LYMPHOMA: MATURE FOLLOW UP AND DERIVATION OF A NOVEL PROGNOSTIC SCORE FROM THE TROG99.03 TRIAL

Introduction: The TROG99.03 represents the only randomised phase III trial of combined modality therapy (CMT) in limited-stage follicular lymphoma ‘LSFL’, reporting a prolonged progression-free survival (PFS) in the CMT arm (MacManus, JCO, 2018). Here, we report extended follow up of this study providing mature data of patients treated with a rituximab-containing CMT regimen and the development of a new gene-expression based prognostic score. Methods: Patients with LSFL, grade 1–3a were randomised (1:1) to either involved-field radiotherapy alone (IFRT) (30–36Gy) or to CMT consisting of identical IFRT followed by 6 cycles of CVP. Reflecting evolving clinical practice, from 2006 onwards (i.e., ‘modern-era’), PET staging was increasingly utilised, and rituximab added to the CMT arm. Digital multiplex gene expression by Nanostring was performed on diagnostic biopsies based on genes previously identified to differentiate LSFL from advanced stage FL ‘ASFL’ (AM Staiger, Blood, 2020). Results: 150 patients were recruited between 2000 and 2012 with 31/75 patients in each arm recruited in the ‘modern-era’. At median follow-up 11.3 years, PFS remained superior for CMT compared to RT (HR 0.6; p = 0.043). Although no significant difference in OS was observed (HR 0.45, p = 0.11), compared with IFRT, patients in the CMT arm experienced fewer composite (deaths and histological transformation ‘HT’) events (HR 0.25; p = 0.045). With additional follow up no new non-malignant late toxicities were observed and incidence of secondary malignancies were similar between both arms (11 IFRT vs. 10 CMT, p = 0.99). Patients treated with a rituximab regimen (i.e., IFRT+R-CVP) had a markedly superior PFS compared to those treated without rituximab (i.e., IFRT, or IFRT+CVP), 8 year PFS rates 81% versus 52%, HR 0.42 p = 0.013 (Figure 1). Amongst PET staged patients the difference between R-CVP/IFRT versus IFRT increased (HR 0.35 p =0.027) suggesting this effect was not due to stage migration. No clinical factors were significantly associated with PFS on multivariate analysis. Nor were prognostic associations found for expression level of any individual genes. However, by penalised Cox regression an 8-gene Lasso-weighted prognosticator was identified, termed the ‘Bio-LSFL-score’. Genes (CACNA2D2, CD69, GZMB, IL7R, MYCT1, SLP1, TNFRSF14, TNFRSF25) reflected both B-cells and the microenvironment. The Bio-LSFL-score was highly significant for PFS (HR 0.25, p < 0.0001) with 100% patients in the high-risk group relapsing before 8 years. Conclusions: Particularly when incorporating rituximab, LSFL patients demonstrated significant increases in PFS and reduction in the rates of death and/or HT when treated with CMT compared with IFRT alone. A novel gene expression prognosticator was identified which in this trial cohort showed ‘ASFL-like’ behaviour by identifying LSFL patients unlikely to experience durable remissions. Keywords: diagnostic and prognostic biomarkers, indolent non-Hodgkin lymphoma, radiation therapy Conflicts of interests pertinent to the abstract C. Cheah Consultant or advisory role: Roche, Janssen, Gilead, Astra Zeneca, Lilly, TG Therapeutics, Beigene, Novartis, Menarini, Daizai, Abbvie, Genmab, BMS Research funding: BMS, Roche, Abbvie, MSD, Lilly J. F. Seymour Consultant or advisory role: Abbvie, Astra Zeneca, Celgene/BMS, Genentech, Genor Bio, Gilead, Janssen, Morphosys, Roche, Sunesis, TG Therapeutics Research funding: Celgene/BMS M. K. Gandhi Research funding: Beigene, Janssen

Glomerular filtration rate is an independent prognostic factor in patients with B-large cell lymphoma.

Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0-1, intermediate risk = 2-3 and high risk = 4-5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder.

Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count<.5×109 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p=.014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p<.001). PJP was associated with mortality within 90days of diagnosis (p<.001), but not after 90days (p=.317). PJP was also associated with 90-day death-censored renal allograft loss (p=.026). PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90days. PJP prophylaxis should be considered in SOT recipients with PTLD.

Use of obinutuzumab in therapy of patients with newly diagnosed follicular lymphoma. Experience of the Oncohematology Division of the Clinical Hospital “Lapino”

Follicular lymphoma (FL) is the most common indolent form of lymphoma and characterized by recurrent course and heterogenous clinical signs. Selection of treatment program for patients with newly diagnosed or recurrent FL is based primarily on the size of the tumor. While use of rituximab-containing regimens led to increased progression-free survival, in some cases tumors are refractory to rituximab. Understanding of molecular mechanisms of FL pathogenesis and action of anti-CD20 monoclonal antibodies allowed to develop new drugs with several advantages compared to rituximab. According to the data of large randomized trials, use of glycoengineered monoclonal anti-CD20 type II antibody obinutuzumab in combination with chemotherapy in patients with FL has manageable toxicity profile and longer progression-free survival and event-free survival compared to use of rituximab.

Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Introduction: Currently, the standard of care for patients (pts) with relapsed/refractory (RR) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment is salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) in appropriately selected, chemosensitive pts. Following first-line therapy (tx) with a rituximab-containing anthracycline-based regimen in the modern era, response rates to platinum-based chemoimmunotherapy are suboptimal. More effective salvage regimens for RR DLBCL remain an unmet need. Polatuzumab vedotin (Pola) is an antibody-drug conjugate directed against CD79b that is safe and effective when combined with chemotherapy in frontline and relapsed, transplant-ineligible DLBCL pts [Tilly NEJM 2022, Sehn, JCO 2020]. We evaluated the safety and efficacy of Pola combined with rituximab, ifosfamide, carboplatin, and etoposide (RICE) as second-line tx in RR DLBCL in a multicenter phase 2 study. Methods: Adult transplant-eligible pts with ECOG ≤ 2 who had biopsy-proven RR DLBCL following frontline CD20-directed anthracycline-based chemoimmunotherapy were eligible. Pts with DLBCL not otherwise specified (NOS), transformed indolent lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma (HGBCL) NOS, and HGBCL with MYC and BCL2 rearrangements were eligible. Pts with central nervous system lymphoma, peripheral neuropathy (PN) ≥ grade (gr) 2 or prior tx of RR DLBCL were excluded. Participants received PolaR-ICE: 1.8mg/kg Pola day (d) 1, rituximab 375mg/m2 d1, etoposide 100 mg/m2 IV d1-3, carboplatin AUC 5 (750 mg max) IV d2, ifosfamide IV 5000 mg/m2 d2 (inpatient) or divided between d1-3 (outpatient) every 21d for 2 cycles followed by PET-CT. G-CSF prophylaxis was mandatory. Pts in CR were eligible to proceed directly to ASCT or could receive a 3rd cycle of PolaR-ICE at investigator's discretion. Pts with partial response (PR) [or stable disease, MD discretion] received a 3rd cycle of PolaR-ICE. After ASCT, pts in ongoing response who had recovered from ASCT toxicities were eligible to receive Pola consolidation (1.8mg/kg) in 21d cycles starting d+30-60 to complete a cumulative 6 doses of Pola. A safety lead-in of up to 8 pts were enrolled according to the IQ rolling 6 design, with a de-escalation dose available (Pola 1.4mg/kg). Following the lead-in, a 2-stage design was employed with 20 pts enrolled (including lead-in) and since 8+ CRs were observed, the study proceeded to enroll a total of 40 pts. The co-primary endpoints were safety and CR rate according to 2014 Lugano classification. ORR, PFS and overall survival were secondary endpoints. Results: 41 pts were enrolled; baseline characteristics are shown in Table 1. 37 pts were evaluable for response: 1 pt died prior to response assessment, 1 pt was inevaluable for response and replaced, 1 pt had clinical progressive disease (PD) and counted in ORR evaluation as PD, and 1 pt is pending response evaluation. 40 pts have toxicity data available, including 22 pts who received 3 cycles of PolaR-ICE, 16 treated with 2 cycles to date, and 2 pts who received 1 cycle to date. Of 38 pts (37 evaluable + 1 clinical PD), 35 had an objective response after 2 cycles of PolaR-ICE for an ORR of 92%, 21 (55%) had a CR, 14 (37%) had a PR, 1 had stable disease and 2 had PD. The end of salvage (PolaR-ICE x 2 or 3) ORR was 89% and CR rate 61% (1 PR became PD and 2 PR converted to CR with a 3rd cycle). To date, 21 pts proceeded to ASCT and 13 pts received consolidation Pola. The most common treatment-emergent adverse events (TEAE, all gr) related to PolaR-ICE were anemia (78%), nausea (70%), thrombocytopenia (70%), leukopenia (50%), fatigue (48%), neutropenia (48%), lymphopenia (38%), constipation (35%), hypertension (30%), and hypophosphatemia (28%). The most common gr ≥ 3 TEAEs were anemia (43%), thrombocytopenia (43%), neutropenia (43%), and no other non-hematologic TEAE occurred in more than 2 (5%) pts. 1 pt underwent Pola dose reduction due to gr 4 cytopenias, gr 2 nausea. Gr ≥ 3 infection/febrile neutropenia/sepsis occurred in 3 (8%) pts. 1 pt had a study treatment-related gr 5 AE due to sepsis. PN occurred in 10 (25%) pts, all gr 1 except one gr 2 event. Conclusion: PolaR-ICE produced a high ORR with CR in a majority of pts and the safety profile was similar to RICE, without added toxicity due to Pola. Longer follow-up is needed to assess the durability of responses and outcomes following ASCT/Pola consolidation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Type II Glycoengineered Humanized Anti-CD20 Monoclonal Antibody MIL62 Combined with Orelabrutinib in Chinese Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma: Updated Results of a Multicenter, Phase I/IIa Trial

Background: A novel glycoengineered type II anti-CD20 antibody, MIL62 with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Orelabrutinib (ICP-022) is a novel and highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor that does not affect IL2-associated tyrosine kinase (ITK) or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combined therapy with anti-CD20 antibodies. Methods: This was a phase I/IIa dose escalation and dose expansion study (NCT 04304040), which investigated MIL62 combination with orelabrutinib for the treatment of patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) with received at least one prior systemic regimen. The dose escalation was conducted with a standard 3+3 dose scheme in different dose combinations of MIL62 injection 800 mg or 1000 mg plus orelabrutinib 100 mg or 150 mg oral daily up to 120 weeks or until disease progression, or intolerable toxicity, respectively. The primary endpoint was objective response rate (ORR), defined as a complete response (CR) or partial response (PR) assessed by investigator per Lugano 2014 criteria. The secondary endpoints were duration of response, pharmacokinetics, and safety. Adverse events (AEs) were graded by CTCAE version 5.0. Results: From July 28th, 2020 to January 26th, 2022, 43 patients enrolled from 10 centers in China received at least one dose of either MIL62 or orelabrutinib. Diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) accounted for 72.1% (31), 16.3% (7), 9.3% (4) and 2.3% (1), respectively. Median age was 66.0 (range: 31 to 77) years and 29 (67.5%) patients had ECOG PS score of 1-2. The median number of prior therapies was 2.0 (range: 1 to 7) and 22 (51.2%) patients were primary resistant to rituximab-containing regimens. The median treatment time of MIL62 and orelabrutinib was 4.7 (range: 0.2, 17.5) months and 3.9 (range: 0.2, 14.1) months, respectively. At the cut-off date (July 15th, 2022), the median OS follow-up time was 13.0 (95% confidence interval [95% CI]: 12.2, 15.0) months. Overall, 27 (64.3%) of 42 assessable patients had an objective response, including 13 (31%) with CR and 14 (33.3%) with PR. In addition, among 30 assessable patients with DLBCL, 17 (56.7%) patients had an objective response, including 7 (23.3%) with CR and 10 (33.3%) with PR. The median progression-free survival (PFS), 9-month remission rate and 12-month overall survival rate were 5.8 ([95%CI]: 3.9, Not reached) months, 71.4%, 73.0%, respectively. Especially, in 20 patients with resistance to rituximab, 10 (50%) patients had an objective response, and median PFS was 5.6 months (Table 1). Among 43 safety-evaluable patients, treatment emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) occurred in 39 (90.7%) patients, 38 (88.4%) patients respectively. Grade 3 or above TEAE were observed in 20 (46.5%) patients, among which TRAEs in 16 (37.2%) patients, with neutropenia (20.9%), thrombocytopenia (16.3%). Severe adverse events (SAEs) occurred in 14 (32.6%) patients, among which 11 (25.6%) were TRAEs. 4 (9.3%) patients were permanently stopped the study due to TEAEs. The incidence of MIL62 infusion-related reactions was 11.6%, all of which were grade 1-2. Conclusion: MIL62 combined with orelabrutinib showed promising efficacy in previously treated patients with r/r DLBCL, including those with resistance to rituximab, and has a manageable safety profile. Keywords: MIL62; type II anti-CD20 monoclonal antibody; r/r B-NHL; DLBCL; Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination

Vaccines having aided in escaping the majority of the population from immunological naïvety, our strategies are now shifting towards an increased focus on identifying and protecting the extremely vulnerable. We here describe the results of testing 12 patients, those with lymphoid malignancies having been targeted their B-cells for therapy with rituximab-containing regimens or a Bruton tyrosine kinase inhibitor, for anti-SARS-CoV-2 spike antibodies after receiving the BNT162b2 mRNA vaccine doses. The interval from last dosing of B-cell depletion therapy to SARS-CoV-2 vaccination was at median 5.3 (range 3.1–6.6) months. Using the ‘seroprotection’ threshold of 775 [BAU/mL] for the anti-spike antibody titer, our finding points out the crucial unresponsiveness of the targeted population with 0/12 (0%) achieving ‘seroprotection’. Although IgG seroconversion was observed in 4/12 (33%), supporting the overall benefit of vaccination, the figures still point out a potential need for optimization of practice. IgA was further less responsive (unsuccessful ‘seroconversion’ in 11/12 (92%)), implicating an underlying class switch defect. Those with depletion on B-cells are caught at a dilemma between, being too early and too late on receiving SARS-CoV-2 vaccines. They wish to get over their immunological naïvety at the earliest, while, in order to assure quality immune memory, are also required to hold the patience for their B-cells to repopulate. Although it remains an issue whether intensified vaccine schedules and/or regimens will lead to stronger immunogenicity or more effective boosters for non-responders, we shall take advantage of every increasing evidence in order to optimize current options.

Rituximab Treatment of Primary Cutaneous Follicle Center Lymphoma: A Retrospective Review.

Primary cutaneous B-cell lymphoma (PCBCL) presents only in the skin at the time of diagnosis with no evidence of extracutaneous disease, and primary cutaneous follicle center lymphoma (PCFCL) is the most common subtype. There is currently a lack of prospective randomized control trials and large retrospective studies investigating the efficacy of different treatment options for PCFCL. This retrospective study was conducted to describe our local clinical experience and outcomes of patients treated with rituximab-containing regimens. To describe our local clinical experience and treatment outcomes of patients treated with rituximab-containing regimens. A retrospective study consisting of 25 PCFCL patients treated with different modalities. Patient records were reviewed and analyzed using a Kaplan-Meier estimation and SAS 9.4 software. After the initial treatment, all patients had CR except for 1 patient in the observation group. Further, 60% of patients in surgery, 20% in chemoimmunotherapy, 67% in rituximab monotherapy, 33% in steroid injection/systemic prednisone, and 33% in observation experienced a relapse. Although no significant difference was found between treatment groups due to the small sample size, time to relapse trends provides insight into treatment responses. Chemoimmunotherapy had the lowest relapse rate in the first 5 years post-treatment, whereas surgery had a higher tendency to relapse. Despite the potential for rituximab-containing chemoimmunotherapy to yield adverse effects, it is effective in achieving a prolonged clinical remission in patients with PCFCL. It remains a reasonable treatment option for diffuse, extensive, or treatment-resistant disease.

High baseline total lesion glycolysis predicts early progression of disease within 24months in patients with high-tumor-burden follicular lymphoma.

Despite the introduction of rituximab-containing regimens, approximately 20% of patients with follicular lymphoma (FL) still experience progression of disease within 24months (POD24) and have poor overall survival. Therefore, a more accurate risk assessment tool is required. We investigated the predictive value of two new volume-based parameters determined from baseline 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), baseline total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), in 45 patients with high-tumor-burden FL who underwent baseline PET/CT. We observed that high TMTV, high TLG, and poor initial treatment response (less than complete [metabolic] response [non-CR/CMR] at the end of induction therapy) independently predicted poor PFS. Notably, POD24-positive patients were more common in the high-TLG group than in the high-TMTV group, which suggests that TLG is a stronger predictor of outcomes than TMTV. Combining baseline TLG and initial treatment response showed that patients with both high TLG and non-CR/CMR experienced significantly poorer outcomes, with a 2year PFS of 0% (hazard ratio 60.39, P = 0.000002). This combination had 56% sensitivity and 100% specificity for detecting patients who would experience POD24. Baseline TLG and initial treatment response can precisely identify patients at high risk of POD24.

Population-wide patterns of care in mantle cell lymphoma in Australia: An analysis of the pharmaceutical benefits scheme dataset.

e19587 Background: The treatment landscape in patients with mantle cell lymphoma (MCL) is changing with the introduction of Bruton’s tyrosine kinase inhibitors (BTKis) and bendamustine in Australia. We sought to analyze the practice impact of the introduction of publicly funded novel agents in MCL. The objective of this study was to describe the evolving treatment patterns of Australian patients with MCL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for MCL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, which includes the dispensing records for 10% of the Australian population. This dataset captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for MCL. First-line (1L) therapy was defined as the first treatments prescribed for MCL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess the changes in the treatment patterns. Results: Overall, 241 patients with MCL were identified over the study period. The majority of patients were male (68.4%), age &gt; 60 years (84.9%), and most being aged 70-79 years (42.1% of total). Many patients were receiving comedications at baseline, including antihypertensives (44.1%), anticoagulants (14.5%), and/or antipsychotics or antidepressants (12.5%). In the overall population (2011-2021), the majority of patients had received 1L treatment with bendamustine-rituximab (BR, 53.9%), rituximab plus other regimens (27.6%), or rituximab monotherapy (11.2%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included BTKi (66.3%), rituximab monotherapy (52.8%) or rituximab plus other regimens (31.5%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 for 1L therapy, the use of BR increased from 0% to 50% and use of rituximab-containing regimen except BR decreased from 100% to 16.7%; use of BTKi increased in R/R patients from 0% to 74.7%. Conclusions: MCL treatment patterns have significantly changed in Australia since the introduction of BTKis and bendamustine-containing regimens. The use of rituximab-containing regimens except BR in 1L MCL has decreased and use of BTKis in R/R patients has increased.