Abstract CT140: Pilot study of “hyperfractionated” anti-prostate specific membrane antigen (PSMA) radioimmunotherapy (177Lu-J591) for progressive metastatic castration-resistant prostate cancer (mCRPC)
Authors: Molina Ana M. , Batra Jaspreet S. , Karir Beerinder S. , Jhanwar Yuliya , Vallabhajosula Shankar , Christos Paul J. , Lam Linda , Epstein Jennifer , Karpenko Irene , Beltran Himisha , Nanus David M. , Goldsmith Stanley J. , Bander Neil H. , Tagawa Scott T. 
Published: July 2016

Abstract
Background: Phase I and II single dose 177Lu?J591 studies have been published demonstrating safety and efficacy in mCRPC. We reported a study of fractionated-double dose 177Lu?J591 (2 doses given 2 weeks apart), demonstrating the ability to administer higher cumulative doses with a dose-response and also equal or less toxicity. As a single-dose, 70 mCi/m2 results in at least 30% declines in 47% with 41% receiving a platelet transfusion. When administered in 2 divided doses, 80 mCi/m2 results in 25% PSA response with 25% transfusion; 90 mCi/m2 results in 59% response with 65% getting transfused. We hypothesize that additional dose-fractionation will allow a higher cumulative dose with less toxicity.
Methods: Patients with progressive mCRPC with normal neutrophil and platelet counts were enrolled in a planned 6-patient pilot study. No selection for PSMA expression was performed. 177Lu-J591 was administered at 25 mCi/m2 every 2 weeks until the emergence of grade 2 myelosuppression. Planar imaging of 177Lu?J591 at 6?8 days following the 1st and 4th doses was performed. Pre- and post-treatment PSA and CTC counts (CellSearch) were measured.
Results: 6 men median age 68.5 (range 50-79), PSA 84.8 (14.7-2265), 67% elevated LDH, 83% unfavorable CTC count, 67% prior chemo, all prior exposure to abi/enza. Five (83%) with bone mets, 5 (83%) with lymph node mets, and 2 (33%) with visceral mets. Pts received a range of 3-6 doses (cumulative 75-150 mCi/m2 of 177Lu-J591). Two (33%) had &gt;30% PSA decline and 3 (50%) had CTC count decline. Two (33%) experienced Gr 4 neutropenia (without fever), 3 (50%) had Gr 4 thrombocytopenia, and 2 (33%) had platelet transfusion. Two had worsening cytopenia following partial count recovery during periods of cancer progression, with bone marrow biopsies in both revealing infiltrative tumor without dysplasia. Targeting of 177Lu?J591 at known sites of disease was seen in all (100%) pts.
Conclusions: “Hyperfractionation” of radioimmunotherapy with 177Lu?J591 is possible in a heavily pre-treated population with poor prognostic features. Targeted delivery of 177Lu occurs to known sites of disease in an unselected patient population. Study is ongoing to determine the optimal target population and dosing regimen for phase 2 study.
Citation Format: Ana M. Molina, Jaspreet S. Batra, Beerinder S. Karir, Yuliya Jhanwar, Shankar Vallabhajosula, Paul J. Christos, Linda Lam, Jennifer Epstein, Irene Karpenko, Himisha Beltran, David M. Nanus, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Pilot study of “hyperfractionated” anti-prostate specific membrane antigen (PSMA) radioimmunotherapy (177Lu-J591) for progressive metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT140.