Integration of cell therapies and bispecific antibodies into the treatment pathway of relapsed diffuse large B-cell lymphoma

Rampotas, Alexandros; Sangha, Gina; Collins, Graham P.

doi:10.1177/20406207211053120

Cited by 7 publications

(3 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Salvage therapy with high-dose chemotherapy and autologous stem cell transplant (ASCT) has historically been the standard of care for patients with relapsed/refractory (R/R) DLBCL 3 , 4 , 5 ; however, less than half of patients with R/R DLBCL will be suitable candidates for ASCT, and of those who are eligible, half will relapse after ASCT. 6 Before the availability of anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, survival outcomes for patients with R/R DLBCL who were unsuitable for second-line treatment with aggressive salvage chemotherapy and who had received at least 2 previous lines of therapy, were especially poor 6 , 7 , 8 , 9 , 10 ; the SCHOLAR-1 study showed that the median overall survival (OS) duration for patients with refractory disease was 6.3 months from the start of salvage therapy.…”

Section: Introductionmentioning

confidence: 99%

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma

et al. 2023

View full text Add to dashboard Cite

As part of a phase 1/2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received >=2 prior lines of therapy). Intravenous mosunetuzumab was administered with cycle (C)1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory. Patients with complete response (CR) completed treatment after C8; those with partial response or stable disease continued treatment for a total of 17 cycles. The primary endpoint was CR rate (best response) by Independent Review Facility, assessed against a historical control CR rate (20%). Eighty-eight patients (73.9% de-novo DLBCL; 26.1% transformed follicular lymphoma) were enrolled; all had received prior anthracycline and anti-CD20 therapy. Overall response and CR rates were 42.0% (95% confidence interval [CI], 31.6-53.1) and 23.9% (95% CI, 15.4-34.1, respectively; CR rate did not reach statistical significance versus the historical control [P = 0.36]). Median time to first response was 1.4 months. Median progression-free survival was 3.2 months (95% CI: 2.2, 5.3). The CR rate in 26 patients who received prior CAR-T therapy was 12%. CRS was one of the most common adverse events (26.1% of patients); predominantly grade 1 to 2 and primarily in C1. Four patients (4.5%) discontinued mosunetuzumab due to adverse events. Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts.

show abstract

Section: Introductionmentioning

confidence: 99%

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma

et al. 2023

View full text Add to dashboard Cite

show abstract

“…CAR-T therapy carries risk of cytokine release syndrome and neurologic toxicity ( 8 ) and ASCT involves intensive multiagent chemotherapy and multiweek hospitalization. Moreover, many patients either are not eligible for or do not respond to these therapies, and ultimately progress and die of their disease ( 9 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

Real-world evaluation of health-related quality of life in patients with diffuse large B-cell lymphoma based on a multinational survey

Johnson,

Bailey,

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

BackgroundReal-world health-related quality of life (HRQoL) data in patients with diffuse large B-cell lymphoma (DLBCL) are scarce. This study is to compare patient-reported outcomes in patients with DLBCL across therapy lines and countries.MethodsData were derived from the Adelphi DLBCL Disease Specific Programme™ from January 2021 to May 2021, a survey of physicians and their DLBCL patients in France, Germany, Italy, Spain, United Kingdom (UK), and the United States (US).ResultsOverall, analysis was conducted on 441 patients with DLBCL across Europe and the US (mean age 64.6 years, 64% male); 68% had an Ann Arbor stage III and 69% had an Eastern Cooperative Oncology Group Performance Status of 0 to 1. The mean overall GHS/QoL was 54.1; patients on their 3L+ therapy had a lower mean GHS/QoL compared with patients on 1L/2L (P = 0.0033). Further to this, mean EQ-5D-5L utility score was reduced from 0.73 for patients on 1L therapy to 0.66 for patients on 3L+ therapies (P = 0.0149). Mean percentages of impairment while working and overall work impairment were lower for patients receiving 3L+ therapy (12.5% and 17.7%; respectively) than those on 1L therapy (35.6% and 33.8%; respectively). When comparing region, patients in the US had significantly better scores for all functioning and symptomatic scales (per EORTC QLQ-C30) and work impairment (per WPAI) vs. patients with DLBCL in Europe. WPAI scores indicate that the overall activity impairment in the US was 36.6% and in Europe ranged from 42.4% in the UK to 54.9% in Germany. Mean EQ-5D-5L utility score for the US was 0.80, compared to 0.60 – 0.80 across the countries in Europe. Regression analysis showed patients who relapsed after more than one year of treatment were associated with better patient reported outcomes than those who relapse after less than one year.ConclusionPatient-reported outcomes of DLBCL patients remain poor and patients continue to experience considerable morbidity.

show abstract

“…This includes T cell receptor (TCR)-transgenic T cells and chimeric antigen receptor (CAR) T cells that can bind to unprocessed antigens on the cell surface and do not require additional co-stimulatory signals. CD19 CAR T cells are now the standard of care for certain types of refractory lymphomas and leukemias [5] and solid cancer indications for CARs have shown promising results [6]. There are also multiple preclinical studies and ongoing clinical trials to support that CARs can be effective in glioma [7][8][9], however, CAR T cells have not entered routine clinical practice for GBM [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma

Hunger,

Schregel,

Boztepe

et al. 2023

Theranostics

View full text Add to dashboard Cite

Rationale: Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) including chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cell therapy targeting glioma-associated antigens are an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred T cells homing to the glioma microenvironment are currently lacking. Methods: Ultrasmall iron oxide nanoparticles (NP) can be visualized non-invasively by magnetic resonance imaging (MRI) and dedicated MRI sequences such as T 2 * mapping. Here, we develop a protocol for efficient ex vivo labeling of murine and human TCR-transgenic and CAR T cells with iron oxide NPs. We assess labeling efficiency and T cell functionality by flow cytometry and transmission electron microscopy (TEM). NP labeled T cells are visualized by MRI at 9.4 T in vivo after adoptive T cell transfer and correlated with 3D models of cleared brains obtained by light sheet microscopy (LSM). Results: NP are incorporated into T cells in subcellular cytoplasmic vesicles with high labeling efficiency without interfering with T cell viability, proliferation and effector function as assessed by cytokine secretion and antigen-specific killing assays in vitro . We further demonstrate that adoptively transferred T cells can be longitudinally monitored intratumorally by high field MRI at 9.4 Tesla in a murine glioma model with high sensitivity. We find that T cell influx and homogenous spatial distribution of T cells within the TME as assessed by T 2 * imaging predicts tumor response to ACT whereas incomplete T cell coverage results in treatment resistance. Conclusion: This study showcases a rational for monitoring adoptive T cell therapies non-invasively by iron oxide NP in gliomas to track intratumoral T cell influx and ultimately predict treatment outcome.

show abstract

Integration of cell therapies and bispecific antibodies into the treatment pathway of relapsed diffuse large B-cell lymphoma

Cited by 7 publications

References 60 publications

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma

Real-world evaluation of health-related quality of life in patients with diffuse large B-cell lymphoma based on a multinational survey

In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma

Contact Info

Product

Resources

About