Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: sPCL are found in relapsed/refractory MM (RRMM) with multiple lines of disease progression, The use of BCMA-CART in multiple myeloma has extended survival for many patients, but it is less commonly studied in sPCL. Aims: To assess the efficacy and safety of BCMA-CART in patients with secondary plasma cell leukemia(sPCL), as well as to investigate the consolidation regimen and timing of application in patients who achieved PR after CART. Methods: Patients with sPCL who met the entry criteria were enrolled and treated with BCMA-CART after lymphatic clearance pretreatment regimens, with some patients later receiving allogeneic transplantation(Allo-SCT) for consolidation, to assess the efficacy and safety of this treatment. Results: A total of 8 patients with sPCL were included in our study center from 2020.12 to 2022.11, with a male proportion of 6/8 (75%); 4/8 (50%) patients <45 years old, median age was 48.5 years; 8 patients had DS stage III, with 7/8 (87.5%) in group A; 3/8 (37.5%) were in ISS andR-ISS stage II,5/8 (62.5%) were in ISS and R-ISS stage III; mSMART3.0 stage were all in the high-Risk group, with Double Hit Myeloma accounting for 5/8 (62.5%); only 1 patient with extramedullary lesions; median CPC and range were 22% (6%-77%) respectively; proportion of previous treatment lines 5 (62.5%) and median line 3.5 (1-7); 8/8 (100%) patients were all resistant to lenalidomide, 4/8 (50%) were resistant to pomalidomide, 8/8 (100%) were all resistant to bortezomib, 2/8 (25%) were resistant to carfilzomib, and 8/8 (100%) were all resistant to daratumumab; only 3/8 (37.5%) patients had SCT history.The median and range of peak BCMA-CART amplification was 16 (11-28) days; the best outcome after BCMA-CART was PR in 6 patients, with ORR at 1 and 2 months after CART being 6/ 8 (75%) 4PR,2VGPR.Three of the six patients who achieved remission underwent Allo-SCT for consolidation therapy three months after CART, two patients are still alive with sCR, and one patient relapsed and died one month after consolidation therapy with Allo-SCT; the other three patients did not undergo Allo-SCT and consolidation therapy with CART for financial and medical reasons, and one relapsed and died 6 months after CART, one relapsed and died 1 year and 3 months after CART, and one is still alive. One case died after a one year and 3 months after CART relapse. and one case is still in the VGPR follow-up phase;The median follow-up time was 186.5 days, and the 6-month PFS and OS rates were 62.5% and 60%, respectively. BCMA-CART treated CRS Grade 1 ratio was 4/8(50%), Grade 2 was 2/8(25%), Grade 4 was 2/8(25%); all 8 patients had no ICANS; anemia Grade3 was 8/8(100%), neutropenia Grade2 was 1/8(12.5%), Grade3 was 7/8(87.5%), thrombocytopenia Grade3 was 1/8(12.5), Grade4 was 7/8(87.5%);nausea/vomiting Grade 1 was 4/8 (50%) and Grade 3 was 4/8 (50%); two patients died within one month of returning to CART due to severe pneumonia and gastrointestinal haemorrhage; two patients who died early had up to 70% abnormal peripheral blood plasma cells; and one patient developed pulmonary Aspergillus infection three months after returning to CART. Summary/Conclusion: BCMA-CART therapy can provide short-term relief for patients with sPCL, It is recommended that patients who achieve PR after CART undergo Allo-SCT for consolidation therapy as soon as possible to obtain deep remission and achieve long-term survival.Keywords: Multiple myeloma, Allo-SCT, CAR-T, B-cell maturation antigen
ABSTRACT Objective Currently, chimeric antigen receptor T‐cell (CART) therapy represents a highly effective approach for relapsed/refractory B‐cell lymphomas. However, it also carries treatment‐related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B‐cell lymphomas. Therefore, we conducted a retrospective cohort study to address this gap in knowledge. Methods During the period from May 2019 to August 2022, a total of 26 patients recurrent/refractory with recurrent/refractory B‐cell lymphoma involving the gastrointestinal tract enrolled. Pathology confirmed CD19 antigen expression in tumor tissues. The disease status of patients who failed multiple lines of therapy was progressive disease (PD). Before CART cell infusion, patients received an FC regimen (fludarabine and cyclophosphamide) lymphodepletion. Quantitative PCR and flow cytometry were adopted for monitoring CART cell kinetics and function, with a focus on gastrointestinal AEs during treatment. The overall response rate (ORR) of the 26 patients was 61.5% (16/26), while the complete response rate (CR) was 23.1% (6/26). Their median follow‐up time was 22.49 months, while the medians of overall survival (OS) and progression‐free survival (PFS) were 10.88 and 5.47 months, respectively. The 1‐year OS and PFS rates were 45% and 42.3%, respectively. The prevalence of gastrointestinal complications was 21/26 (80.7%), including gastrointestinal hemorrhage in 11/26 (42.3%), emesis and diarrhea in 9/26 (34.6%), as well as intestinal obstruction in 2/26 (7.7%). A total of three patients (3/26, 11.5%) died of gastrointestinal hemorrhage. The gastrointestinal hemorrhage group exhibited markedly lower ORR and inferior OS compared to the non‐hemorrhage group. Conclusion Generally, the CART cell therapy is valid in relapsed/refractory B‐cell lymphoma with gastrointestinal involvement, but gastrointestinal bleeding is a unique risk factor that requires special attention, particularly in patients with high gastrointestinal tumor burden, as it is associated with poor efficacy and survival.
Background and aims Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16–0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27–0.8; p=0.005). Conclusion CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.
Objective. The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. Methods. The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. Results. Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively ( ). The median progression-free survival was 16.3 (2.6–24.5) months, and the median overall survival was 19.3 (6–24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS ( ) and OS ( ). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. Conclusion. The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.
Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: The prognosis of refractory/relapsed B-cell lymphoma (r/r B-NHL) is extremely poor, especially for those patients who have failed therapy with CAR -T. Although the benefit was observed with Pola-based salvage therapy, long-term survival was unsatisfactory, particularly in patients who did not intend to bridge to subsequent therapy. Aims: Our objective was to evaluate the efficacy of Pola-based salvage therapy and as a bridge to CAR -T-cell therapy in r/r B-NHL patients, including response rates, progression-free survival (PFS), and overall survival (OS). Methods: We analyzed the use of Pola-based salvage therapy between June 2020 and January 2023.Ninety-four patients were included: 53/94 (56.4%) male; median age 49 (18-80). Diagnoses included DLBCL NOS (n=68), HGBL (n=7), PMBCL (n=5), TFL (n=5), BL (n=6), and other (n=3). 91/94 (96.8%) patients were at stage III-IV at the time of salvage therapy. The median IPI score was 3 (range 1-5). 80/94 (85.1%) patients had extranodal lesions. 34/94 (36.2%) patients had > 7 cm bulky disease. Patients had received a median of 3 (range 1-8) prior lines of treatment. 13/94 (13.8%) and 19/94 (20.2%) patients had failed prior autologous hematopoietic stem cell transplantation and prior anti-CD19 CAR -T cell therapy, respectively. 46/94 (48.9%) patients received Pola-based therapy (salvage cohort) and 48/94 (51.1%) patients were treated with Pola-based therapy as bridging CAR -T-cell therapy (bridging cohort), including 19 patients after failure of prior anti-CD19 CAR -T. The median number of pola-based cycles was 3 (1-8) for the salvage cohort and 3 (1-6) for the bridging cohort. 48/94 (51.1%), 11/94 (11.7%), and 35/94 (37.2%) of patients received PB/PBR, P-GMox/ ICE, and Pola in combination with other chemotherapy regimens, respectively. Prior to the study, the expression of CD19/CD20/CD22/CD79b antigens in tumour tissue was confirmed by pathology and the different CAR targets were selected for patients who failed anti-CD19 CART cell therapy. Results: The best ORR for the salvage and bridging cohorts was 58.54% and 41.46%, respectively (P=0.1164). In the bridging cohort, the ORR was 44.4% for patients who had failed prior chemotherapy and 26.3% for patients who had failed prior CD19 CAR -T (P=0.2098). CD79b antigen status was determined in 55/94 patients (58.5%), with 44/55 (80%) having antigen expression greater than 80%. The median follow-up time was 15.8 (range 8.8-18.3) months. In the salvage cohort, 6-month PFS and OS were 11.1% and 23.4%, respectively. In comparison, PFS and OS were significantly longer in the bridging cohort, resulting in 6-month PFS of 51.5%(P=0.0003) and OS of 61.3%(P=0.0008).In the bridging cohort, 6-month PFS (PFS 36.8% vs. 51.5%,P=0.2178)and OS (52.6% vs.61.3%,P=0.2176)were shorter in patients who had failed prior CD19 CAR -T cell therapy than in patients who had not been treated with CAR -T cell therapy.Although there was no statistical difference, the survival curves showed poor late survival in the group of patients in whom CAR -T had failed.(Figure 1).In each case, calculated from the start of Pola-based therapy.Significant factors for prolonged PFS on multivariate analysis were bridging CAR -T therapy (p< 0.0001), more cycles for Pola-based therapy (p =0.0001), and ORR achieved in the first two cycles (p=0.002). Summary/Conclusion: This study provides new insights into the timing of Pola-based salvage therapy in patients with refractory/relapsed B-cell lymphoma. In patients eligible for CAR -T cell therapy, early administration of Pola-based treatment as a bridge before CAR -T would significantly improve survival.Keywords: relapsed/refractory, CAR-T, B cell lymphoma, Salvage chemotherapy
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