Hodgkin lymphoma is typically considered to be one of the most curable forms of cancer, but some with the disease relapse or find that their cancer is resistant to treatment.
For patients like this, a fully human monoclonal antibody called avelumab has shown promising results in a phase 1 clinical trial for safety and efficacy.
The drug works by preventing a protein called PD-L1 from doing its job, which is to suppress the immune system. By putting PD-L1 in check, the body can better fight against relapsed or treatment-resistant (refractory) classical Hodgkin lymphoma in patients who have previously been treated with other drugs and therapies.
“The main takeaway from our results is that PD-L1 inhibition is effective and safe in patients with relapsed or refractory Hodgkin lymphoma,” said City of Hope’s Robert W. Chen, M.D.
, assistant professor in the Department of Hematology &Hematopoietic Cell Transplantation, who presented trial results at the 2017 International Conference on Malignant Lymphoma biennial meeting in Lugano, Switzerland, in mid-June. Several other City of Hope researchers were also in attendance.
The results were from the multicenter JAVELIN Hodgkin study that enrolled 31 patients with classical Hodgkin lymphoma who either experienced disease progression after a stem cell transplant or were ineligible for that line of treatment. Participants were randomized to receive one of five dosing regimens of avelumab. After a median duration of 16.9 weeks, the disease control rate was 71 percent and tumor shrinkage of more than 50 percent was achieved by 23 patients.
The incidence of treatment-related side effects was similar across all trial participants and included infusion-related reactions, nausea, rash and fatigue. Two trial participants discontinued treatment due to immune-related events, and no treatment-related deaths were reported.
Previous immunotherapies have targeted PD-1, an immune checkpoint that binds to PD-L1 and second protein called PD-L2. However, success with avelumab may mean that only the PD-L1 protein needs to be targeted with treatments. Avelumab also differs from other immunotherapies by directly targeting tumor cells rather than T cells and has demonstrated anti-tumor activity in lung, bladder and renal cancer, according to results from other JAVELIN Solid Tumor trials.
Among study participants, avelumab had the greatest benefit in eight postallogeneic stem cell transplant patients (meaning they received their transplanted cells from donors) who demonstrated an objective response rate of 62.5 percent, with two patients achieving a complete response, meaning that their cancer was undetectable. Three patients achieved a partial response, or significant decrease in tumor size. According to Chen, this type of response among postallogeneic stem cell transplant patients suggests that the PD-L1 blockade may boost the donor stem cells’ power in fighting the lymphoma.
“Based on these findings, the next step of the study will focus on patients who have relapsed after allogeneic transplant, as that is a difficult population with an unmet need,” said Chen.