Parsaclisib in Non-Hodgkin Lymphoma
by Dr. C.H. Weaver M.D. 3/2020
Cancers that begin in cells of the lymph system are referred to as malignant lymphomas. Lymphomas range from aggressive to slow growing or indolent. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes and circulating white blood cells called lymphocytes. Lymphocytes and the lymph system are part of the immune system that protects the body from disease and infection. Cancers of the lymph system are referred to as Hodgkin lymphoma or non-Hodgkin lymphoma (NHL).
The majority of lymphomas can be effectively treated, and optimal treatment of lymphoma may consist of chemotherapy, radiation, stem cell transplant, CAR T cells, radio-immunotherapy (RIT) precision cancer medicines and immunotherapies used alone or in combination. Despite all these treatments some patients with lymphoma still succumb to their cancer and new treatments are needed.
Parsaclisib is a phosphatidylinositol 3-kinase-δ inhibitor (PI3K), that is being developed for the treatment of different types of B-cell malignancies and systemic lupus erythematosus, the initial focus is advanced B cell lymphomas. The PI3K pathway promotes cancer cell proliferation, growth, motility, metabolism and survival and the disruption of this pathway with precision cancer medicines can prevent certain cancers from growing and spreading.
Researchers have reported the initial results of an early phase clinical trial of parsaclisib in patients with relapsed or refractory B-cell malignancies. In this study parsaclisib was administered alone or in combination with the Janus kinase 1 inhibitor (itacitinib) or “RICE” chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide) to patients with refractory NHL.
Overall 72 patients received parsaclisib monotherapy at various dose levels. The most common side effects observed were diarrhea/colitis (36%), nausea (36%), fatigue (31%), and rash (31%). In NHL the objective response rates to monotherapy with parsaclisib were significant: 71% in follicular lymphoma, 78% in marginal zone lymphoma, 67% in mantle cell lymphoma, and 30% in diffuse large B-cell lymphoma (DLBCL).
Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes. A second trial has further assessed parsaclisib in patients with relapsed or refractory DLBCL in reported similar response rates and the trial is ongoing in a combination study Clinical trial information: NCT02998476.
Blood. 2019 Apr 18;133(16):1742-1752. doi: 10.1182/blood-2018-08-867499. Epub 2019 Feb 25.