bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline treatment with zanubrutinib plus rituximab (ZR) followed by short course R-DHAOx in patients with mantle cell lymphoma (MCL): Results of the phase II CHESS clinical trial.
Authors: Cai Qingqing , Xia Yi , Huang Huiqiang , Li Zhiming , Huang He , Li Guowei , Zhang Yuchen , Cao Yi , Gao Yan , Liu PanPan , Fang Xiaojie , Mie Man , Tian Xiaopeng , Sun Xiuhua , Pan Xueyi 
Published: June 2024

7062 Background: Combining Bruton’s tyrosine kinase (BTK) inhibitor and rituximab showed favourable efficacy as first-line therapy for mantle cell lymphoma (MCL). Zanubrutinib, a next-generation, highly-selective BTK inhibitor, achieved promising antitumor activity in MCL. In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination, followed by short course cytarabine-based chemotherapy, then zanubrutinib maintenance as frontline therapy for MCL (NCT04624958). Methods: Previously untreated MCL patients enrolled and received induction therapy of ZR until complete response (CR) or to a maximum of 12 cycles, and followed by 4 cycles of R-DHAOx regimen (rituximab, dexamethasone, cytarabine and oxaliplatin). Patients achieving CR after chemotherapy would receive maintenance therapy with zanubrutinib for a maximum of 1 year. The primary endpoint was CR rate after induction therapy with ZR regimen. Minimal residual disease (MRD) of bone marrow and peripheral blood were evaluated by flow cytometry. Results: From Oct 2020 to Nov 2023, a total of 42 patients were enrolled and the enrollment was finished. The median age was 57 years (IQR, 51-64). Stage III-IV accounted for 92.8%, and 42.8% were intermediate or high risk simplified MIPI. Thirty-four patients (81.0%) were classic histological subtype. The median cycle of ZR was 4 (range, 2-6). As of Jan 2024, among 37/42 patients with post-treatment PET evaluation, the best CR rate of ZR regimen was 91.9% (34/37), and 94.1% (32/34) obtained CR after 2-4 cycles. The bone marrow MRD negative CR rate was 92.0% (23/25). The other 5/42 patients were still receiving ZR treatment, and PET evaluation would be performed subsequently. Among 27 patients who finished chemotherapy and were evaluable for response, only one patient experienced disease progression. With a median follow up of 11.6 months, the 1-year progression-free survival and overall survival was 90.1% and 96.7%, respectively. Two patients died due to lymphoma (n=1) and COVID-19 (n=1). Grade 3-4 adverse events on ZR regimen were neutropenia (n=3), fatigue (n=2), and aminotransferase (n=1). During chemotherapy, grade 3-4 thrombocytopenia was observed in 75.8% of patients. Conclusions: Induction treatment with ZR followed by short-course R-DHAOx chemotherapy yielded promising antitumor efficacy. This strategy might reduce the toxicity of cytarabine-based chemotherapy without weakening the therapeutic efficacy. Clinical trial information: NCT04624958 . [Table: see text]
A phase 1 study of SHR-A1912, a CD79b targeted antibody-drug conjugate (ADC), in patients (pts) with B-cell non-Hodgkin lymphoma (B-NHL).
Authors: Li Zengjun , Xie Yang , Ni Shuqin , Zhou Hui , Chen Junmin , Huang Pinfang , Yang Wei , Zheng Li , Zou Liqun , Wang Yike , Liu Yiming , Ma Dahua , Mao Wenjun , Zhu Jun , Song Yuqin 
Published: June 2024

7064 Background: CD79b is an attractive therapeutic target for B-NHL. SHR-A1912 is a novel ADC containing an anti-CD79b monoclonal antibody conjugated to the DNA topoisomerase I inhibitor. Here, we present results of the dose-escalation (D-ESC) and dose-expansion (D-EXP) parts of a first-in-human phase 1 study of SHR-A1912 in B-NHL. Methods: Pts with histologically confirmed B-NHL that had failed to respond to or had progressed after ≥1 prior anti-cancer therapy were enrolled. The D-ESC part commenced with accelerated titration at 0.1 and 0.3 mg/kg and then switched to an i3+3 scheme at escalated doses starting from 0.6 mg/kg (Q3W, IV). In the D-EXP part, additional pts were enrolled to selected doses (approximately 10–12 pts in total per dose level). Primary objectives were to assess the safety and tolerability of SHR-A1912 and determine the RP2D. Results: As of Nov 7, 2023, 49 pts were enrolled (n=1, 1, 7, 3, 13, 13, and 11 in the 0.1, 0.3, 0.6, 1.2, 1.8, 2.7, and 3.6 mg/kg dose cohorts), including 33 pts with diffuse large B-cell lymphoma (DLBCL), 12 with follicular lymphoma (FL), and 4 with marginal zone lymphoma (MZL). Pts had received a median of 2 lines of prior treatment (range, 1–9). DLTs occurred in 3 pts during D-ESC (grade 4 decreased neutrophil count lasting ≥3 days in 0.6 and 3.6 mg/kg cohorts, 1 pt for each; grade 3 pneumonia in 2.7 mg/kg cohort, 1 pt). The 1.8, 2.7, and 3.6 mg/kg cohorts were expanded. Overall, grade ≥3 treatment-related adverse events occurred in 20 (40.8%) pts, with the most common (≥20%) being decreased neutrophil count. 41 pts with baseline target lesions had at least one post-baseline assessment; ORR was 56.1% (95% CI, 39.8–71.5), and 6-mo DoR rate was 62.7% (95% CI, 26.7–84.8). As for subtypes, ORR was 51.9% in pts with DLBCL (57.1% and 77.8% in the 2.7 and 3.6 mg/kg cohorts, respectively), 63.6% in pts with FL, and 66.7% in pts with MZL (Table). The mean half-life of conjugated antibody ranged from 4.7 to 5.3 days for pts in the 1.8–3.6 mg/kg cohorts, with volume of distribution close to human plasma volume. The plasma exposure of free toxin was low, with the molar ratio of toxin/conjugated-antibody <1%, and no accumulation was observed. Conclusions: SHR-A1912 was tolerable up to 3.6 mg/kg and had promising anti-tumor activity in pts with previously treated B-NHL, supporting further investigations of SHR-A1912. Clinical trial information: NCT05113069 . [Table: see text]
Incidence of central nervous system relapse in primary mediastinal B-cell lymphoma: Implications for central nervous system prophylaxis.
Authors: Okcu Izel , Zhou Jihao , Wang Yucai , Bock Allison Marie , Alhaj Moustafa Muhamad , Baidoun Firas , Tun Han W. , Rosenthal Allison Claire , Johnston Patrick B. , Kabat Brian , Rimsza Lisa M. , Habermann Thomas Matthew , Nowakowski Grzegorz S. 
Published: June 2024

7080 Background: Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of aggressive B-cell non-Hodgkin lymphoma. PMBCL has distinct clinicopathologic features compared to diffuse large B-cell lymphoma but shares some clinical and biologic features with nodular sclerosis classic Hodgkin lymphoma (cHL). Central nervous system (CNS) relapse is exceedingly rare in cHL, therefore one may expect that CNS relapse in PMBCL is also uncommon. Herein, we examined the incidence of CNS relapse in patients with PMBCL. Methods: Patients with newly diagnosed PMBCL seen at Mayo Clinic between 1/2002 and 4/2023 were identified from the Mayo Clinic Lymphoma Database. Clinical features, treatment details and outcomes were abstracted from medical records. The CNS relapse rate was calculated using a competing risk model, with death considered as a competing risk. Results: A total of 154 PMBCL cases were identified. The median age at diagnosis was 38 years (range 18-77) and 60.4% were female. The distribution of CNS-IPI was low-risk in 80 (51.9%) patients, intermediate-risk in 43 (27.9%), and high-risk in 3 (1.9%), and data were missing for 28 patients (18.2%). 78 patients (50.6%) received R-CHOP and 76 patients (49.4%) received R-DA-EPOCH as frontline therapy. High-dose methotrexate (HD-MTX) for CNS prophylaxis was administered to 5 patients (all treated with R-CHOP). 20 patients received intrathecal (IT) chemotherapy (methotrexate and/or cytarabine) for CNS prophylaxis (4 with R-CHOP [1 received HD-MTX too],16 with R-DA-EPOCH). The median follow-up was 39 months (95% CI 28.2-49.8). Only 3 patients had CNS relapse, all associated with systemic relapse (1 concurrent, 1 had CNS relapse 8.8 months after systemic relapse, 1 had CNS relapse 2 months before systemic relapse). The cumulative incidence of CNS relapse for the entire cohort was 1.43% (95% CI 0.3%-4.6%) at 1 year and 2.21% (95% CI 0.6%-5.8%) at both 2 and 5 years. For those who did not receive CNS prophylaxis (n=130), the incidence was 0.86% (95% CI 0.1%-4.3%) at 1 year and 1.82% (95% CI 0.4%-5.8%) at both 2 and 5 years. All 3 patients who experienced CNS relapse had R-CHOP as frontline therapy; two patients did not receive any CNS prophylaxis, while 1 patient received IT CNS prophylaxis. Conclusions: The risk of isolated CNS relapse in PMBCL appears to be very low, even in patients who did not receive CNS prophylaxis. While some patients may experience CNS relapse associated with systemic relapse, the overall incidence was low (1.43% at 1 year and 2.21% at 2 and 5 years). The rarity of isolated CNS relapse in PMBCL suggests that routine CNS prophylaxis may not be necessary as part of initial therapy.
Outcomes and prognostic factors of patients diagnosed with relapsed/refractory primary B-cell lymphoma: A retrospective study.
Authors: Dumke Henry , Phillips Tycel Jovelle , Kaminski Mark S , Carty Shannon , Wilcox Ryan A. , Sano Dahlia , Kandarpa Malathi , Polk Avery , Karimi Yasmin 
Published: June 2024

7081 Background: PMBCL is an aggressive form of large B-cell lymphoma (LBCL) but has a unique gene expression profiling signature that more closely resembles Hodgkin’s lymphoma. Treatment of R/R PMBCL is largely extrapolated from trials in LBCL with few PMBCL patients included. Randomized trials leading to use of CART as second line treatment for patients with primary refractory or early relapsed LBCL enrolled ≤ 10% PMBCL patients (ZUMA-7 and TRANSFORM). In the rituximab era, there is a paucity of data on the efficacy and outcomes of salvage therapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT/ASCT) in PMBCL. Methods: We conducted a retrospective study of patients with PMBCL, histologically confirmed at the University of Michigan, diagnosed between 2001 and 2023. Results: 70 patients were included with a median age of diagnosis of 31.5 years and 57% female. R-DA-EPOCH was the most commonly used first line therapy (FLT) in 58 patients (83%). 10 patients (14%) were treated with R-CHOP with or without consolidative radiation. 65 patients had end of treatment (EOT) PET/CT: 45 (69%) patients achieved a Deauville (D) 1-3 response, 15 (23%) had D4 response, 5 (8%) had D5 response. 4 (26%) of patients with D4 response and all patients with D5 response ultimately developed R/R disease. 5 had EOT response assessed by CT and all deemed to have complete response. 16 patients (23%) developed R/R disease with a median time to relapse of 8.3 months. All relapses occurred within 2 years: 5 patients with primary refractory disease, 10 patients with relapse <12 months and only 1 patient with relapse >12 months. Platinum based chemotherapy with RICE, RDHAP or RGemOx were the most common salvage regimens (N=11) with ORR 60% among evaluable patients. 5 patients received HDT/ASCT with ORR of 80% and CR rate of 80%. Only 1 patient progressed following ASCT, who had relapsed >12 months after FLT. 9 patients (13%) had high-risk extranodal disease (EN) such as renal, adrenal or breast sites with 2 patients (11%) developing CNS relapse. At a median follow up time of 6.5 years, 5-year PFS and OS for the entire cohort was 76% and 96%, respectively. For patients with R/R disease, 5-year PFS and OS was 49% and 84%, respectively. Conclusions: We report high response rates to platinum-based salvage chemotherapy in the rituximab era, even with primary refractory or early relapsed disease. Higher PFS and OS suggests improved outcomes with HDT/ASCT compared to historical outcomes in R/R LBCL (SCHOLAR-1). Larger prospective studies are needed to determine whether HDT/ASCT or CART is the optimal approach in R/R PMBCL. [Table: see text]
Outcomes of patients who received CAR T cell therapy and developed IEC-HS treated with cytokine directed therapy.
Authors: Leung Nelson , Alkhateeb Hassan B. , Atallah-Yunes Suheil Albert , Durani Urshila , Gallo De Moraes Alice , Gupta Supriya , Hayman Suzanne R. , Herrmann Joerg , Johnston Patrick B. , Kenderian Saad , Khurana Arushi , Puttkammer Jenna R , Rees Matthew J. , Sandahl Tyler B , Vergidis Paschalis , Warsame Rahma M. , Wolf Robert C. , Lin Yi 
Published: June 2024

7516 Background: Immune effector cell hemophagocytic lymphohistiocytosis IEC-HS is a complication of CAR T cell therapy (CART). This study aims to look at the outcomes of CART patients who develop IEC-HS. Methods: Patients who developed IEC-HS after receiving CART and patients who developed IEC-HS without (nonCART) between December 2020 and March 2022 were included. Results: The 20 CART patients were older than the 25 nonCART patients. Peak ferritin, fibrinogen, CRP, serum creatinine and transaminases were similar between the 2 group. CART patients had lower white blood cell count and platelets and bilirubin than the nonCART patients. CART patients were more like to have markedly elevated IL-6 levels (> 315 mg/ml), higher IL-18, higher MCP-1, and suppressed IL-1β and GMCSF than nonCART patients (Table). Treatment of IEC-HS included tocilizumab (n = 19), anakinra (n = 18) siltuximab (n = 4) and basiliximab (n = 4), dexamethasone (n = 18) methylprednisolone (n = 6), etoposide (n = 1) and ruxolitinib (n = 1). A significant response defined by a 90% reduction or normalization of the cytokine was observed with IL-10 and IFN-ϒ in 92.3% and 84.6% of the CART patients respectively. An intermediate response was noted with TNF, IL-6, MCP-1 and MIP-1 in 38.4%, 30.8% and 61.6% and 38.5% of the patients respectively. No patient had a significant response in IL-2Rα or IL-1β and only 7.7% had a significant response in IL-18. Of the 5 patients who had a MIP-1 response, 4 were on basiliximab +/- high flow continuous venovenous hemofiltration and the only patient that had an IL-18 response was on both modalities. The 100-day mortality after IEC-HS in the CART patients was 40% and was associated with higher peak and lower best ferritin but not the percentage reduction (Table). Higher TNF (90.3 pg/ml vs 37.2 pg/ml, p = 0.05), markedly elevated levels of IL-6 (92% vs 50%, p = 0.03) and IL-10 (33% vs 0%) and an IL-6 response (44.4% vs 0%) were associated with survival at day 100. IL-6 responders had lower peak ferritin vs IL-6 nonresponders (14066 mcg/L vs 45051 mcg/L, p = 0.08). Enterococcus faecium bacteremia developed in 75% of the nonsurvivors vs 16.6% of the 100-day survivors (p = 0.009). Survivors cleared the enterococcus bacteremia within days while nonsurvivors had protracted bacteremia. Conclusions: IEC-HS is devastating complication of CART. Anti-cytokine therapy can reduce some cytokines and ferritin but overimmunosuppression may lead infectious complication, in particular with E. faecium. Better biomarkers are needed to finetune immunosuppressive therapy in order to avoid over-immunosuppression. [Table: see text]
Real world outcome of patients with multiple myeloma who received bispecific antibodies after CAR-T therapy.
Authors: Bansal Radhika , De Menezes Silva Corraes Andre , Brunaldi Larissa , Sandahl Tyler B , Rees Matthew J. , Hayman Suzanne R. , Binder Moritz , Abdallah Nadine , Dingli David , Cook Joselle , Gertz Morie A. , Kapoor Prashant , Kourelis Taxiarchis , Warsame Rahma M. , Kumar Shaji , Lin Yi 
Published: June 2024

7520 Background: There are 2 CAR-T products and 3 bispecific antibodies (BsAbs) that are FDA-approved for patients (pts) with relapsed, refractory multiple myeloma (MM). Clinical trials experience to date suggests that clinical response of BsAb is less impacted after CAR-T therapy. We examined the outcome of pts who received BsAb in standard-of-care (SOC) practice at Mayo Clinic Rochester. Methods: Retrospective analysis of MM patients who received FDA-approved BsAb at Mayo Clinic, Rochester between 12/2022- 1/2024. IMWG criteria was used for clinical response. Results: Sixty-two patients received BsAbs: 77% (48/62) received teclistamab, and 23% (14/62) received talquetamab. Median age was 62 years (range: 33-81), 60% (37/62) were males, and 45% (28/62) received prior CAR-T. Patients who had prior CAR-T therapy had more prior lines of therapy compared to those who did not. Overall, ORR to teclistamab was 61%, which is comparable to previous studies and other real-world reports. ORR and ≥CR rates were comparable between patients with and without prior CAR-T (Table). Of the 28 pts who received CAR-T before BsAbs, 61% (17/28) received idecabtagene vicleucel, 10% (3/28) were ciltacabtagene autoleucel, and 29% (8/28) on clinical trial. We then compared outcome of BsAb between pts who had relapsed from CAR-T within 1 year (n=21, median PFS: 8.84 months (range, 1.12, 10.84)) or after 1 year (n=7, median PFS: 16.62 months (range, 13.30, 36.20)). At the time of BsAb infusion, pts with who relapsed < 1 year vs ≥1 year post CAR-T had comparable blood counts, ALC, M-protein and involved FLC levels, CRP, ferritin and LDH. BsAb CR/sCR rate was significantly higher in pts with disease relapse ≥1 year compared to <1 year post CAR-T (57% vs 14%, p=0.02). Conclusions: Irrespective of prior CAR-T exposure, BsAb have clinical activity in SOC practice in pts with MM. Our preliminary data suggest that responses to BsAbs are better in pts with late compared to early relapse post CAR-T. Longer follow-up is needed to understand the duration of response. Larger, multi-center studies with longer follow-up will help identify factors that impact BsAb response post CAR-T.[Table: see text]
Post-ASCT consolidation with EPD or ERD in patients with high-risk multiple myeloma.
Authors: Zolotov Eli , Kabat Maciej , Parmar Harsh , Anand Palka , Zenreich Josh , Aleman Adolfo , Phull Pooja , Vesole David H. , Siegel David Samuel DiCapua , Biran Noa 
Published: June 2024

7534 Background: Patients (pts) with high-risk (HR) Multiple Myeloma (MM), characterized by at least two cytogenetic abnormalities often experience rapid disease progression and early relapse post-autologous stem cell transplant (ASCT) with median Progression-Free Survival (PFS) of 24 or 12 months with or without lenalidomide maintenance (Panopoulou et al, Blood 2023). This study assesses the efficacy and safety of EPD (Elotuzumab, Pomalidomide, Dexamethasone) or ERD (Elotuzumab, lenalidomide , Dexamethasone) as consolidation therapy post-ASCT in HR MM pts. Methods: In this single-center retrospective study, we reviewed records of MM pts treated with consolidative ERD or EPD from September 2016 to March 2023. We collected baseline MM characteristics, treatment history, adverse events (AEs), and survival outcomes. HR MM pts were defined by 2 or more cytogenetic abnormalities (del 17p, 1q21 gain or amplification, t(14;16), t(14;20), complex karyotype) and/or high-risk gene expression profiling scores (GEP, SKY92). All patients, aged ≥21, underwent ≥1 full cycle of EPD or ERD post-ASCT, administered for a total of four 28-day cycles, following the standard dosing regimen with a rapid dexamethasone taper over the last two cycles. Results: A total of 78 HR MM pts, median age 64 years with 51.2% males and 71.7% caucasians were included. Of them, 62 pts received ERD and 16 received EPD. FISH revealed 62.7% of pts had 2 or more high risk cytogenetic abnormalities. Other pts expressed a combination of cytogenetic abnormalities and/or high-risk GEP or SKY92 scores. The table shows improvement in MRD negativity rates from 21.7% to 26.9% pre and post consolidation, and in VGPR or better from 78.2% to 85.8%. Median PFS for all pts, defined from the time of ASCT to disease progression, was 26.9 months. Most common adverse effects were anemia (71.7%), fatigue (55.1%) and thrombocytopenia (51.2%). Five patients experienced grade 3 adverse events, including 3 with infectious etiology (3.8%) and 2 with immune-mediated toxicity (2.5%). No treatment-related serious adverse events were reported. Conclusions: Four cycles of EPD or ERD consolidation therapy post-ASCT, demonstrated promising efficacy in HR MM pts. The observed median PFS of 26.9 months was comparable to that seen with chronic lenalidomide maintenance and superior to patients who do not receive lenalidomide maintenance. The improvement in PFS was achieved with a fixed duration rather than continuous therapy and without lenalidomide-associated toxicities such as secondary malignancies, chronic diarrhea, and financial toxicity. Further prospective confirmatory studies are needed. [Table: see text]
Real-world schedule de-escalation of teclistamab in patients with relapsed/refractory multiple myeloma.
Authors: Tan Carlyn Rose Co , Derkach Andriy , Maclachlan Kylee , Hultcrantz Malin , Hassoun Hani , Mailankody Sham , Shah Urvi A , Rajeeve Sridevi , Shah Gunjan L. , Scordo Michael , Chung David J. , Landau Heather Jolie , Giralt Sergio , Lesokhin Alexander M. , Korde Neha , Lin Dee , Wu Bingcao , Fowler Jessica , Fernandez Mariana , Usmani Saad Zafar 
Published: June 2024

7536 Background: Teclistamab (Tec) is the first BCMAxCD3 bispecific antibody approved for triple-class-exposed relapsed/refractory multiple myeloma (RRMM). The MajesTEC-1 study demonstrated an overall response rate (ORR) of 63% and a median progression-free survival (mPFS) of 11.3 months (mos). Herein, we examined real-world pt characteristics and outcomes associated with Tec in (1) pts treated within the first 4 mos of Tec approval (early initiators who were expected to have high disease burden) as compared to recent initiators, and (2) any pts who switched to de-escalated dosing schedules. Methods: This is a retrospective study of pts with RRMM treated with Tec at Memorial Sloan Kettering Cancer Center from 11/29/22 to 11/30/23 (analysis cut-off: 12/31/23). Responses were evaluated per IMWG Response Criteria. Pt characteristics were summarized by frequency (%) or median (interquartile range [IQR]). PFS was evaluated using the Kaplan-Meier method. Results: In 77 pts who received ≥1 Tec dose, the median age was 70 (IQR 63-77); 55% male; 14% Black; and 42% had high-risk cytogenetic abnormalities (HRCA). The ORR was 62% for 69 response-evaluable pts, including 42% with ≥very good partial response (VGPR). The median time to first response was 1.9 mos (IQR 1.0-2.4). After a median follow-up (mFU) of 7.6 mos, 6-mo PFS rate was 52.3% (95%CI 41.5-66%). The median duration of response has not been reached. In the cohort of early initiators (n=34), pts had more prior lines of therapy (LOT; median 8 vs 5, P=0.002) and higher proportion of prior BCMA therapy use (62% vs 23%; P=0.002) as compared to recent initiators treated after 3/31/23 (n=43). ORR was 67% and 59%, respectively (P=0.80; Table). Among all pts at data cut-off, 25 (32%) switched from weekly to every-other-week or monthly Tec after a median time of 3.1 mos from Tec initiation (95%CI 1.8-4.6) and based on achieving ≥PR and/or toxicity. At mFU of 5.3 mos since switching, 6-mo PFS rate was 94.1% (95%CI 83.6-100%). Conclusions: In this real-world study, Tec demonstrated comparable ORR to MajesTEC-1. Both early and recent Tec initiators had high baseline risk features. A higher proportion of early initiators had prior BCMA therapy and more LOTs, but both cohorts yielded consistently high treatment response rates. In pts who responded, schedule de-escalation was feasible with a high subsequent 6-mo PFS. Updated multicenter findings will be presented at the meeting. [Table: see text]