Main Session
Sep
28
PQA 04 - Breast Cancer, Patient Reported Outcomes/QoL/Survivorship, Functional Radiation Medicine, Hematologic Malignancies, Palliative Care, and International/Global Oncology
2846 - RadVax for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy
Presenter(s)
Miguel Perez-Guillermo Cuev, MD - IMED Hospitales, Philadelphia, PA
S. Ramesh1, J. Baron1, M. Perez-Guillermo Cuev Sr1, M. Huang2, J. Svoboda3, S. D. Nasta3, D. J. Landsburg3, M. D. Farwell4, S. Schuster3, M. M. Kim1, E. J. Wherry5, S. Somalwar1, K. Clark1, W. Xu1, J. P. Plastaras1, and M. J. LaRiviere1; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Perelman School of Medicine, Philadelphia, PA, 3Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, 4Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, 5Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s):
Relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) has modest complete response (CR) rates with PD-1 blockade. Low-dose radiotherapy (RT) may enhance systemic antitumor immunity (RadVax concept). We conducted a phase II trial evaluating whether low-dose involved-site RT combined with pembrolizumab improves CR rates in r/r NHL. The primary outcome was CR rate (of both in and out-of-field disease) after RT plus pembrolizumab induction. Secondary endpoints included time to response, progression-free survival (PFS), overall survival, and safety.Materials/Methods:
This phase II study enrolled 6 patients with histologically confirmed r/r NHL after =2 prior therapies. Patients had =2 measurable lesions, including =1 outside the RT field. Patients received involved-site RT to selected lesion(s) at 4 Gy × 5 fractions. Pembrolizumab 400 mg IV every 6 weeks was initiated during or within 3 days of RT completion and continued until progression. Response was assessed by FDG PET/CT using Lugano criteria. The primary endpoint was CR rate among evaluable patients. Toxicity was graded per CTCAE v5.0.Results:
Three patients with diffuse large B cell lymphoma, 1 patient with mantle cell lymphoma, and 2 patients with cutaneous T cell lymphoma were evaluable. No complete responses were observed (0%). Two patients achieved partial response (33%). One patient classified as progressive disease demonstrated complete metabolic response on PET but developed a single new out-of-field cutaneous lesion. Five of 6 patients (83%) had an in-field response, and four (67%) demonstrated at least partial response of some disease out-of-field. In-field responses demonstrated durability, with local control maintained until death or last follow-up among responders. Median time to best response was 43 days (range 20–65). Median PFS was 58 days (range 22–197). At median follow-up of 2 years, 4 of 6 patients (67%) remain alive. Two patients (33%) experienced grade 3 toxicity: skin pain attributed to RT and upper GI hemorrhage possibly attributed to pembrolizumab vs radiation gastritis. No grade 4+ events occurred.Conclusion:
The trial was closed early after enrollment of 6 of a planned 40 patients due to evolving alternate systemic therapies for r/r NHL, which reduced referral and accrual. Despite the limited accrual, several observations were notable. Low-dose RT consistently produced high in-field response rates with durable local control, supporting the intrinsic radiosensitivity of lymphoma even in heavily pretreated patients. At least some degree of out-of-field responses were observed in a subset of patients, suggesting biologic activity of the combination, though this did not translate into durable systemic disease control. In the context of rapidly advancing systemic therapies, future efforts to integrate radiation with immunotherapy in lymphoma may require alternative sequencing, patient selection strategies, or combination partners to meaningfully enhance systemic outcomes.