scholarly journals Safety and Short-Term Efficacy of CART Cells in Treatment of Diffuse Large B-Cell Lymphoma with Follicular Transformation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4845-4845
Author(s):  
Kai Hu ◽  
Shaomei Feng
Keyword(s):  
B Cell ◽  
Disease Progression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Germinal Centers ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Short Term ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background：Tissue transformation to Diffuse large B-cell lymphoma(DLBCL) occurs in some patients with follicular cell lymphoma(FL), and these patients have a poor prognosis, and some patients do not respond well to chemotherapy, relapse or disease progression. In recent years, many clinical trials have found that CART cells are have a relatively good effect on relapsed and refractory DLBCL, but what about the effect on DLBCL transformed by FL? Methods：A total of 13 patients with diffuse large B-cell lymphoma transformed from follicular cell lymphoma who received CART cell therapy in our hospital from January 2020 to January 2021 were observed. All patients had stage III/IV disease (7 patients with stage III and 6 patients with stage IV). Among them, 10 were germinal centers and 3 were non-germinal centers. There were 8 males and 5 females, with a median age of 44 years (33-70 years old), who had undergone more than 2 chemotherapy cycles before admission to our hospital, and the median chemotherapy cycle was 10 cycles (7-19 years old). Among them, 3 had previously undergone other clinical drug trials, 1 had undergone CD20 CART cell immunotherapy, and 1 had undergone radiotherapy. At admission, ECOG was 0-3, and all patients had measurable lesions with a median size of 5cm (1.4cm-12.0cm). After preconditioning, CART cells were reinjected, 12 cases were reinjected with murine anti-CD19-CART, and 1 case was reinjected with humanized anti-CD19-CART. Median volume 3.07×10^6/kg (0.46×10^6/kg -5.43×10^6/kg). The cytokine release syndrome(CRS) and the therapeutic effect of 3 months/6 months after reinfusion were observed, and the endpoint was disease progression or death. Results：The main treatment related adverse reaction was cytokine release syndrome. Among them, there were 12 I CRS, 1 II CRS, and no treatment-related deaths. The short-term efficacy of 3 months after treatment: 4/13CR（30.8%）, 7/13PR（53.8%）, 2/13 SD/PD(15.4%) and ORR was 11/13 (84.6%). The efficacy of 6 months after treatment: 10/13CR（76.9%）, 0/13PR（0%）and ORR was 10/13 (76.9%). One patient with 3-months CR developed disease at 11 months and died at 12 months, and one patient with 3- months PR developed disease at 5 months and died at 8 months. The remaining 6patients with 3- PR have now achieved CR。the median follow-up time was 10 months (6-19months). Of the 2 patients who did not respond to treatment have achieved PR after subsequent treatment. Conclusions: It can be seen from this study that CART cells have obvious efficacy and good safety in the treatment of DLBCL transformed by FL. It should be noted that 7 patients had PR status at 3 months after treatment, 6 patients had CR at 6 months after treatment, and 1 patient had disease progression. Efficacy evaluation of patients with DLBCL with potential transformation from FL after CART cell therapy should be appropriately delayed, except that 6 months may be the best time to evaluate the efficacy. At present, the observation time is short, PFS and OS have not been observed, and long-term observation with a larger sample is under way. Disclosures No relevant conflicts of interest to declare.

scholarly journals Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma

Blood ◽  
2018 ◽  
Vol 132 (8) ◽  
pp. 777-781 ◽  
Author(s):  
Victor A. Chow ◽  
Mazyar Shadman ◽  
Ajay K. Gopal
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Large B Cell Lymphoma ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

Abstract Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy. Durable remissions are seen in 30% to 40% of study-treated patients, but toxicities of cytokine release syndrome and neurotoxicity require administration in specialized centers. This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.

Ofatumumab Monotherapy for Treatment of Patients with Relapsed/Progressive Diffuse Large B-Cell Lymphoma: Results From a Multicenter Phase II Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3955-3955 ◽  
Author(s):  
Bertrand Coiffier ◽  
André Bosly ◽  
Ka Lung Wu ◽  
Gregor Verhoef ◽  
Van Eygen Koen ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Progression ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Large B Cell

Abstract Abstract 3955 Background: Patients (pts) with relapsed diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) or relapsing after ASCT have a poor prognosis and limited therapeutic options. New treatment options are needed for these pts. Ofatumumab is a human monoclonal antibody that targets a membrane-proximal epitope comprising both the large loop and small loop of CD20, and has shown effective lysis of chemotherapy-refractory DLBCL cells in vitro (Teeling et al. Blood 2004; Cillessen et al. Blood 2007; abstract 2346). We report the first results from an open-label, single-arm, international Phase II trial that evaluated ofatumumab monotherapy in relapsed or progressive DLBCL. Methods: Pts (age ≥18 years) with relapsed or progressive CD20+ DLBCL ineligible for ASCT or with relapsed or progressive disease after ASCT were enrolled between December 2007 and August 2009 (N=81). Relapsed or progressive disease was defined as relapse after a complete remission (CR) or disease progression after partial remission (PR). Pts received 8 weekly infusions of ofatumumab (dose 1, 300 mg; doses 2–8, 1000 mg). The primary endpoint was overall response rate (ORR) evaluated during the 6 months from the start of treatment, as assessed by an Independent Endpoint Review Committee according to the revised response criteria (Cheson et al. J Clin Oncol 2007). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS) and safety. Results: Baseline characteristics are shown in the Table. Pts were heavily pretreated (median 3 prior systemic therapies), and 32% of pts did not respond to their last prior therapy. Nearly all pts (96%) had received prior rituximab-containing treatment; 54% had received 2 or more courses of prior rituximab therapy (Table). Overall, 58% of pts completed all 8 infusions of ofatumumab, 65% received at least 6 infusions, and 81% received at least 4 infusions. The primary reason for treatment discontinuation was disease progression. The ORR (95% CI) was 11% (4–18%), including 3 CRs (4%) and 6 PRs (7%). Of these 9 responding pts, 8 had responded to their last systemic therapy. The median duration of response (95% CI) was 6.9 months (5.3–6.9) and median PFS (95% CI) was 2.5 months (2.3–2.9). Infusion-related events occurred in 59% of pts, primarily occurred during infusion 1 (40% of pts) and infusion 2 (22%), and subsided during subsequent infusions; these events were predominantly grade 1–2 in severity (96% of pts). The most common (>10% of pts) adverse events (AEs; any grade) were diarrhea (17%), fatigue (15%), peripheral edema (15%), neutropenia (14%), abdominal pain (12%), constipation (12%), nausea (12%), pyrexia (11%), anemia (11%) and leukopenia (11%). Of these, ≥ grade 3 events included neutropenia (10%), leukopenia (6%), anemia (5%) and fatigue (1%). Grade 3 or greater thrombocytopenia and febrile neutropenia were reported in 6% and 4% of pts, respectively. The most common infectious events were upper respiratory tract infections (7% of pts), all of which were grade 1–2 events. In total, 13 pts died during the study; 3 pts died during the treatment period and 10 pts died during post-treatment follow up (until 24 months from study start). Deaths were due to disease progression (n=10), sepsis (n=1), circulatory collapse (no further details; n=1) and multi-organ failure (n=1). Conclusions: Single-agent ofatumumab was well tolerated with an ORR of 11% in heavily pretreated pts with relapsed or progressive DLBCL, nearly all of whom had received prior rituximab therapy. Response to last systemic treatment appeared to influence response to ofatumumab in this pt population. Further studies of ofatumumab in combination with chemotherapy in relapsed DLBCL are currently underway. Disclosures: Off Label Use: Ofatumumab is an investigational anti-CD20 monoclonal antibody, currently under development for the treatment of B-cell malignancies (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, Waldenstroms macroglobulinemia and follicular lymphoma) as well as autoimmune diseases (rheumatoid arthritis and multiple sclerosis). Davies:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees. Padmanabhan:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Consultancy, Employment. Davis:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees. Losic:Genmab A/S: Employment, Equity Ownership. Lisby:Genmab A/S: Employment. Radford:GlaxoSmithKline: Equity Ownership; Genmab: Consultancy, Honoraria.

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