Subject(s)
Antibodies, Bispecific , Antineoplastic Agents , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Antineoplastic Agents/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Antibodies, Bispecific/therapeutic useABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma in the US. For nearly 2 decades, standard front-line treatment has consisted of chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Numerous trials have unsuccessfully attempted to achieve better outcomes in these patients. Recently, the results of the phase III POLARIX trial were published. This study randomized newly diagnosed DLBCL patients to receive polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) or standard-of-care R-CHOP. The POLARIX trial demonstrated 2-year progression-free survival of 76.7% for pola-R-CHP compared with 70.2% for R-CHOP with comparable safety profiles between the two arms. Based on these results, a new standard of care may be emerging in patients with DLBCL. This article provides a practical approach to managing a newly diagnosed patient with DLBCL.
ABSTRACT
Richter transformation (RT) refers to the development of an aggressive lymphoma in patients with pre-existing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). It carries a poor prognosis secondary to poor response to therapy or rapid disease relapse. Currently there are no randomized trials to guide treatment. Therapeutic decisions are often influenced by the presence or absence of a clonal relationship between the underlying CLL/SLL and the new lymphoma given the poor prognosis of patients with clonally related RT. Chromosomal microarray analysis (CMA) can help to establish clonality while also detecting genomic complexity and clinically relevant genetic variants such as loss of CDKN2A and/or TP53. As a result, CMA has potential prognostic and therapeutic implications. For this study, CMA results from patients with Richter transformation were evaluated in paired CLL/SLL and transformed lymphoma samples. CMA revealed that 86% of patients had common aberrations in the two samples indicating evidence of common clonality. CMA was also useful in detecting aberrations associated with a poor prognosis in 71% of patients with RT. This study highlights the potential clinical utility of CMA to investigate the clonal relationship between CLL/SLL and RT, provide prognostic information, and possibly guide therapeutic decision making for patients with Richter transformation.
