B-Cell Targeted Therapies in Cryoglobulinemia

Author(s):  
Salvatore De Vita
Keyword(s):  
B Cell ◽  
2021 ◽  
Vol 12 ◽  
pp. 204062072198958
Author(s):  
Larysa Sanchez ◽  
Alexandra Dardac ◽  
Deepu Madduri ◽  
Shambavi Richard ◽  
Joshua Richter

Outcomes of patients with multiple myeloma (MM) who become refractory to standard therapies are particularly poor and novel agents are greatly needed to improve outcomes in such patients. B-cell maturation antigen (BCMA) has become an important therapeutic target in MM with three modalities of treatment in development including antibody–drug conjugates (ADCs), bispecific T-cell engagers (BITEs), and chimeric antigen receptor (CAR) T-cell therapies. Early clinical trials of anti-BCMA immunotherapeutics have demonstrated extremely promising results in heavily pretreated patients with relapsed/refractory MM (RRMM). Recently, belantamab mafodotin was the first anti-BCMA therapy to obtain approval in relapsed/refractory MM. This review summarizes the most updated efficacy and safety data from clinical studies of BCMA-targeted therapies with a focus on ADCs and BITEs. Additionally, important differences among the BCMA-targeted treatment modalities and their clinical implications are discussed.


Hématologie ◽  
2021 ◽  
Vol 27 (S1) ◽  
pp. 37-50
Author(s):  
Maxime Jullien ◽  
Steven Le Gouill

2019 ◽  
Vol 61 ◽  
pp. 92-99 ◽  
Author(s):  
Jennifer L Barnas ◽  
Richard John Looney ◽  
Jennifer H Anolik

2019 ◽  
Vol 39 (9) ◽  
pp. 1705-1714 ◽  
Author(s):  
Florentina Porsch ◽  
Christoph J. Binder

2019 ◽  
Vol 72 (9) ◽  
pp. 630-635 ◽  
Author(s):  
Noraidah Masir ◽  
Ariz Akhter ◽  
Tariq M Roshan ◽  
Chandramaya Sabrina Florence ◽  
Faridah Abdul-Rahman ◽  
...  

AimsHeightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.Methods79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).ResultsActivated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).ConclusionsOur data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.


2019 ◽  
Vol 76 (22) ◽  
pp. 1825-1834
Author(s):  
Clement Chung

Abstract Purpose This article summarizes current targeted therapies that have received regulatory approval for the treatment of B- and T-cell lymphomas. Summary Over the last 20 years, new drug therapies for lymphomas of B cells and T cells have expanded considerably. Targeted therapies for B-cell lymphomas include: (1) monoclonal antibodies directed at the CD20 lymphocyte antigen, examples of which are rituximab, ofatumumab, and obinutuzumab; (2) gene transfer therapy, an example of which is chimeric antigen receptor–modified T-cell (CAR-T) therapy directed at the CD19 antigen expressed on the cell surface of both immature and mature B cells; and (3) small-molecule inhibitors (ibrutinib, acalabrutinib, copanlisib, duvelisib, and idelalisib) that target the B-cell receptor signaling pathway. Of note, brentuximab vedotin is an antibody–drug conjugate that targets CD30, another lymphocyte antigen expressed on the cell surface of both Hodgkin lymphoma (a variant of B-cell lymphoma) and some T-cell lymphomas. Although aberrant epigenetic signaling pathways are present in both B- and T-cell lymphomas, epigenetic inhibitors (examples include belinostat, vorinostat, and romidepsin) are currently approved by the Food and Drug Administration for T-cell lymphomas only. In addition, therapies that target the tumor microenvironment have been developed. Examples include mogamulizumab, bortezomib, lenalidomide, nivolumab, and pembrolizumab. In summary, the efficacy of these agents has led to the development of supportive care to mitigate adverse effects, due to the presence of on- or off-target toxicities. Conclusion The therapeutic landscape of lymphomas has continued to evolve. In turn, the efficacy of these agents has led to the development of supportive care to mitigate adverse effects, due to the presence of on- or off-target toxicities. Further opportunities are warranted to identify patients who are most likely to achieve durable response and reduce the risk of disease progression. Ongoing trials with current and investigational agents may further elucidate their place in therapy and therapeutic benefits.


2010 ◽  
Vol 237 (1) ◽  
pp. 264-283 ◽  
Author(s):  
Michael J. Townsend ◽  
John G. Monroe ◽  
Andrew C. Chan

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