A Pilot Study Evaluating Lenalidomide and CC-486 in Combination with Radiotherapy for Patients with Plasmacytoma (LENAZART study)

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.8-10
• Main Authors: Shah, Urvi A, Werner, Kelly, Tavitian, Elizabet, Devlin, Sean, Mailankody, Sham, Korde, Neha, Hultcrantz, Malin, Tan, Carlyn, Lu, Sydney X., Smith, Eric L, Maura, Francesco, Patel, Dhwani, Shah, Gunjan L., Lahoud, Oscar B, Scordo, Michael, Lin, Richard J, Dahi, Parastoo B., Landau, Heather J, Chung, David J., Hassoun, Hani, Landa, Jonathan, O'Malley, Bernard, Barker, Christopher, Merghoub, Taha, Giralt, Sergio A., Landgren, Ola, Yahalom, Joachim, Lesokhin, Alexander M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-141131

Background and Scientific Rationale Solitary plasmacytoma of the bone (SPB) is a rare entity representing 5% of all plasma cell dyscrasias. SPB treated with radiation therapy (RT) has a 10% risk of progression to multiple myeloma (MM) over 3 years if there is no marrow involvement, whereas there is a 60% chance of progression over 3 years in patients with minimal marrow involvement. Median time to progression in the latter group is 26 months. Presently, despite mounting evidence of a significant risk of progression to MM, there is no FDA-approved therapy and patients are usually treated with localized RT. This is an area of unmet need. A similar opportunity exists in the setting of MM patients relapsing with localized disease amenable to RT. This group of patients may not immediately require long-term systemic therapy especially if RT combined with epigenetic modulation and lenalidomide results in therapeutically relevant immune responses. A few studies combining lenalidomide and azacitidine have shown responses even in a lenalidomide refractory population with upregulation of cancer testis antigen (CTA) as well as CTA specific T cell responses (Table 1). These synergistic mechanisms focus on: 1) manipulating antigen expression and enhancing antigen presentation (both neoantigens and cancer testis antigens) with oral azacitidine (CC-486), and 2) augmentation of antigen specific immune responses via increased IL2 production leading to an increase in the proliferation of T cells with lenalidomide. This combination with RT would serve to inflame the tumor microenvironment and potentially lead to therapeutically active systemic immune responses via an abscopal effect. Study Design and Methods This is an open-label, single center, single-arm study of CC-486, lenalidomide plus RT, which will enroll a total of 20 patients in two cohorts. Clinical trial registry number NCT04174196, actively recruiting. Study population and inclusion criteria Each cohort will enroll ten patients - Cohort 1: i) Histologically confirmed newly diagnosed solitary plasmacytoma of the bone or lytic bone lesion ii) Minimal marrow involvement (Detectable clonal bone marrow (BM) plasma cells by multicolor flow cytometry and ≤ 10% clonal plasma cells in a BM biopsy by immunohistochemistry, morphology, or flow cytometry) iii) Secretory M protein < 3 g/dL Cohort 2: i) Relapsed multiple myeloma with plasmacytomas appropriate for RT on imaging ii) Relapsed (reappearance of M-spike/serum FLC) or