P. B. Allen1, A. M. Evens2, B. Pro3, R. Karmali3, H. Savas3, G. Dillehay3, A. Rademaker3, B. Palmer3, R. Advani4, L. I. Gordon3, J. N. Winter3
1Emory University Winship Cancer Institute, Atlanta, GA,2Rutgers Cancer Institute of New Jersey, New Brunswick, NJ,3Robert H. Lurie Cancer Center and Northwestern University, Chicago, IL,4Stanford University, Palo Alto, CA, USA
Background: The PD-1 inhibitor Pembrolizumab (PEM) is US FDA- approved for the treatment of relapsed/refractory cHL based on results of a pivotal trial demonstrating an overall response rate of 69% and complete response (CR) rate of 22%. We initiated a phase 2 clinical trial of sequential PEM and AVD chemotherapy for newly diagnosed cHL. Our primary hypothesis was that PEM monotherapy would result in a CR rate of 50% on interim PET-CT (PET2) based on Lugano Criteria. Herein we report interim results on the first 14 patients enrolled on study.
Methods: Patients > 18 years of age with newly diagnosed cHL stages I-IV, including early stage patients with at least one NCCN risk factor, were eligible. Patients had a pre-therapy PET-CT followed by 3 cycles of PEM at 200 mg every 3 weeks. An interim PET-CT (PET2) was obtained after single agent PEM for primary analysis. Subsequently, patients received 4–6 cycles of AVD chemotherapy based on initial stage. Correlative studies include serum and biopsy samples pre/post PEM to assess immune biomarkers of response.
Results: Fourteen of the planned 26 patients were enrolled from September 2017, through a data cut off of June 1, 2018, at Northwestern University. Median age was 30 years (range, 23–77). Seven patients had early stage unfavorable disease and 7 had advanced stage disease. Eight had bulky disease or large mediastinal masses,7 had elevated ESR's (>50), 5 had B-symptoms, and 6 had extranodal disease. Twelve patients have completed 3 cycles of PEM and undergone PET2 (13 have received at least one dose) and 11 have started AVD. Therapy has been well tolerated. The most common adverse events have been fatigue, anemia, hyperglycemia, arthralgias, hypertension, and hyponatremia, all Grade 1/2. Self-limited Grade 3 diarrhea occurred in one patient following the first infusion. There was one Gr 4 immune-related adverse event (transaminitis) which resolved with steroid therapy and a delay in therapy.
Conclusion: PEM monotherapy (x's 3) in previously untreated patients with cHL has resulted in dramatic responses including CR's and near-CR's particularly in bulky patients (Fig. 1). These early results have prompted the addition of total metabolic volume in addition to standard response criteria to quantify responses and better represent the quality of partial responses. Updated response assessments will be reported at the conference. Treatment has been well-tolerated thus far.