Follicular Lymphoma (closed)
IPH 1101 has been tested in a Phase I/II clinical trial in FL patients. Final data for this trial were presented in June 2010 during the Annual Meeting of the European Hematology Association (“EHA”).
The phase I/II trial in Follicular Lymphoma (the "IPH 1101-202" trial):
The Phase I/II FL study (IPH 1101-202) was an international multicenter trial. The trial aimed at evaluating the efficacy of IPH 1101 associated with low-dose IL-2 in combination with rituximab*, as well as the biological activity and safety of this combination in FL patients with low tumoral mass, relapsing after one to four lines of prior therapy, with at least one rituximab-containing line and who were due to undergo an additional course of rituximab therapy.
The study rationale was based on two data sets:
- the strong, well-established cytotoxicity of γδ T cells vis-à-vis lymphoma cells in cell culture models, and
- pre-clinical results showing synergy between rituximab and IPH 1101 activated γδ T cells in depleting B lymphoma cells through ADCC enhancement.
IPH 1101 therapy was started one week after the first administration of rituximab, and repeated at 3 week intervals for a total of 3 treatment courses. Efficacy was assessed by an independent central review, based on standard response criteria: best overall response (complete and partial responses) within 6 months after treatment.
In France, the trial has been performed with the assistance of the GELA and GOELAMS lymphoma collaborative study groups.
On the 38 evaluable patients assessed by independent central review, 17 patients showed a response (i.e. 45% Overall Response Rate, or “ORR”), including 10 patients showing a complete response (i.e. 26% Complete Response Rate or “CRR”). The complete response rate observed with standard of care (rituximab alone) in similar settings is 40% ORR and 11% CRR (Davis et al., Journal of Clinical Oncology, 2000).
Most patients in the IPH 1101-202 study were “F-carriers” (FcRgamma3a polymorphism - a genotype associated with a poorer response to rituximab-alone therapy). Analysis of the duration of response is ongoing.
Overall, the treatment was well tolerated. The most frequent adverse events were cytokine release related, manageable and reversible.
The final data of the study were reported during an oral by the co-lead investigator of the study, Pr Jean-François Rossi (Head of Hemato-Oncology Department and Center of Clinical Investigation BT 509, University Hospital, Montpellier, France), at the Annual European Hematology Association (“EHA”) Meeting, in Barcelona, Spain.
See the slideshow presented at the EHA meeting
About Non-Hodgkin’s Lymphoma
Non-Hodgkin's lymphoma (“NHL”) includes a heterogeneous group of more than 20 different malignant lymphoproliferative diseases that originate from lymphocytes.
NHL is the sixth most common cause of cancer related death in the United States and the incidence of the disease has increased up to 4% of all new cancer cases in 2009.
The second most frequent clinical entity that is recognised in the new lymphoma classification, after diffuse large B-cell lymphoma, is the follicular lymphoma (22% of all non Hodgkin’s Lymphoma). There were 66,120 new cases of follicular lymphoma in the United States in 2009 (Source: American Cancer Society).
Rituximab, a cytotoxic anti-CD20 monoclonal antibody (CD20 is expressed on the surface of more than 95% of B lymphocytes in NHL), is part of the current standard of care now approved in first line and maintenance therapy as well as in chemoresistant and relapsing follicular lymphoma.
The overall response rate after rituximab retreatment at the time of a relapse is about 40%, justifying the need for additional therapy in this setting.