Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting

Cao, Yang; Marcucci, Emanuela; Budde, Lihua E.

doi:10.1186/s13045-023-01462-0

Cited by 9 publications

(4 citation statements)

References 11 publications

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“…Another agent being explored in the same setting is mosunetuzumab (Lunsumio)-a fully humanized bispecific monoclonal antibody targeting both CD20 and CD3 [112,116]. It is being tested as a monotherapy or combined with atezolizumab (NCT02500407, NCT05091424).…”

Section: Bispecific T-cell Engagersmentioning

confidence: 99%

Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need

Zygmunciak,

Robak,

Puła

2024

IJMS

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Recent years have seen significant improvement in chronic lymphocytic leukemia (CLL) management. Targeting B-cell lymphoma (BCL-2) and Bruton’s kinase (BTK) have become the main strategies to restrain CLL activity. These agents are generally well tolerated, but the discontinuation of these therapies happens due to resistance, adverse effects, and Richter’s transformation. A growing population of patients who have previously used both BTK inhibitors and BCL2 suffer from the constriction of the following regimens. This review explores the resistance mechanisms for both ibrutinib and venetoclax. Moreover, we present innovative approaches evaluated for treating double-refractory CLL.

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Section: Bispecific T-cell Engagersmentioning

confidence: 99%

Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need

Zygmunciak,

Robak,

Puła

2024

IJMS

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“…Mosunetuzumab and polatuzumab vedotin have individually shown promising anti-lymphoma activity and manageable toxicity profiles in patients with R/R NHL 20 , 21 . Mosunetuzumab is an off-the-shelf CD20xCD3 T-cell-engaging bispecific antibody that engages and redirects T cells to eliminate malignant B cells 22 and was recently approved in R/R follicular lymphoma (FL) 23 . Mosunetuzumab, which is administered in an outpatient setting, is efficacious with a favorable toxicity profile in patients with R/R diffuse large B cell lymphoma (DLBCL; NCT02500407 ) 24 , including patients who had received prior CAR-T cell therapy with an overall response rate (ORR) of 42.0% and a complete response rate of 23.9% 20 .…”

Section: Mainmentioning

confidence: 99%

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial

Budde,

Olszewski,

Assouline

et al. 2023

Nat Med

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Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody–drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8–69.0) and 45.9% (45/98; 95% CI: 35.8–56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5–not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2–18.7). Median overall survival was 23.3 months (95% CI: 14.8–NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018.

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“…No bispecific antibodies have been approved for CLL as yet, but since their therapeutic efficacy in B-cell lymphomas has become increasingly evident, 57 more CLL trials are in development. 44 Blinatumomab, a Bi-specific T-cell engagers (BiTEs) monoclonal antibody targeting CD19, has been shown to be effective in a single case of refractory Richter syndrome as a bridge to HSCT, 58 In addition, there are novel immunological strategies currently in development for other hematological malignancies, which could also be applicable to high-risk CLL. 44 One of these is magrolimab, an anti-CD47 antibody, that can harness macrophage-based immunity and enhance phagocytosis.…”

Section: Immunotherapy In the Treatment Of Tp53-disrupted Cllmentioning

confidence: 99%

“…Blinatumomab, a Bi‐specific T‐cell engagers (BiTEs) monoclonal antibody targeting CD19, has been shown to be effective in a single case of refractory Richter syndrome as a bridge to HSCT, 58 and two ongoing clinical trials are evaluating its use in combination with lenalidomide (NCT02568553) or blinatumomab‐expanded T cells (NCT03823365) in patients with different types of Non‐Hodgkin lymphoma (NHL) and high‐risk CLL.…”

Section: Immunotherapy In the Treatment Of Tp53‐disrupted Cllmentioning

confidence: 99%

Targeting TP53 disruption in chronic lymphocytic leukemia: Current strategies and future directions

Molica,

Tam,

Allsup

et al. 2023

Hematological Oncology

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In the modern era of Chronic Lymphocytic Leukemia (CLL) targeted therapy, the loss of p53 function due to genetic abnormalities remains a significant challenge. This is because even targeted agents, which are currently the mainstay of treatment for CLL, do not directly target p53 or restore its disrupted pathway. Consequently, resistance to therapy and unfavorable clinical outcomes often accompany these p53‐related abnormalities. An essential goal of future clinical research should be to address the ostensibly “undruggable” p53 pathway. Currently, multiple therapeutic approaches are being explored to tackle TP53 dysfunction and improve outcomes in high‐risk CLL. These approaches include the use of oncoprotein murine double minute 2 inhibitors, small‐molecule p53 reactivators, exportin 1 (XPO1) inhibitors, and ataxia‐telangiectasia mutated and Rad3‐related (ATR) inhibitors. Combinations of these p53‐targeting strategies, along with established novel therapies such as B‐cell receptor or B‐cell lymphoma‐2 (BCL‐2) inhibitors, may shape the future of therapeutic trials in this challenging‐to‐treat disease.

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Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting

Cited by 9 publications

References 11 publications

Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need

Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial

Targeting TP53 disruption in chronic lymphocytic leukemia: Current strategies and future directions

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