Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Research, adult, Lymphomas, Translational Research, Checkpoint Inhibitor, T Cell lymphoma, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
Methods: Adult patients with histologically confirmed MF or SS, who had failed ≥2 systemic therapies were enrolled and randomized 1:1 to single agent durvalumab (1500 mg (day 1 of 28-day cycle) or durvalumab (same dose) & lenalidomide (10 mg for cycle 1, 15 mg for cycle 2, then 20 mg for subsequent cycles daily for 21 days of each 28-day cycle). The study used a “pick a winner” design based on ORR. Serial skin and blood samples were collected to assess the impact on the tumor microenvironment (TME) and anti-tumor activity.
Results: A total of 23 patients were randomized and had the following characteristics (11 durvalumab vs 12 durvalumab/lenalidomide): median age 57 yrs (35-79) vs 63 yrs (32-88); stage IB, 2 (18%) vs 4 (33%); stage IIB, 4 (36%) vs 3 (25%); stage III/IV, 5 (45%) vs 5 (42%); MF, 8 (73%) vs 8 (67%); e-MF/SS, 4 (36%) vs 2 (17%); large cell transformation 3 (27%) vs 5 (42%). The median number of prior systemic treatments for both single and combo arm was 3. Global best ORR was 58% for durvalumab/ lenalidomide vs 36% for durvalumab alone. Median follow up time was 7.9 (range, 0.9-27.6) months. Analysis is ongoing. One patient died one month after discontinuation from study due to PD. No serious AEs were observed. The most common treatment-emergent adverse events (shown below for combo arm) were more frequent in the durvalumab/lenalidomide arm vs durvalumab arm and included fatigue (n=9), diarrhea (n=4), decreased platelets (n=4), leg edema (n=3), constipation (n=3), hyperglycemia (n=3), anemia (n=3), and leukopenia & neutropenia (n=3). The majority of AEs with both treatment arms were mild to moderate in severity (grade I/II, 91%; grade III, 8 %). No grade IV event except 1 neutropenia on combo arm was observed. Median cycles of treatment were 4 (range, 1-12) and 5 (range 1-7) for single and combo arms.) Five pts remain on treatment on single agent durvalumab vs 3 pts on combo arm. Molecular profiling using CIBERSORT and single cell analysis revealed distinct changes of immune cell signatures and cellular signaling interactions within the TME that occurred in each treatment arm when compared to baseline.
Conclusions: This randomized phase 2 trial of durvalumab (anti-PD-L1) +/- lenalidomide evaluating anti-tumor activity demonstrated superior clinical activity of combinatorial durvalumab/lenalidomide vs single-agent durvalumab in refractory/advanced CTCL. Responses were durable and ongoing, and treatment was well tolerated. Our correlative results from sequential skin biopsies demonstrated immune signatures for enhanced anti-tumor responses on skin biopsies at baseline may be predictive of response to checkpoint blockade and yield insights into mechanisms of therapeutic resistance.
Disclosures: Querfeld: Kyowa Kirin: Consultancy, Honoraria; Helsinn: Consultancy, Honoraria, Research Funding; Citius: Consultancy, Honoraria. Barnhizer: GenMab: Consultancy, Honoraria. Rosen: Pheromone Bio, Inc: Consultancy; Exicure: Consultancy; Apobiologix/Apotex Inc: Consultancy; PharmaGene, LLC: Consultancy; Trillium Therapeutics, Inc: Consultancy; Verastem, Inc: Consultancy; NeoGenomics: Membership on an entity's Board of Directors or advisory committees; Pepromene Bio, Inc: Membership on an entity's Board of Directors or advisory committees; Pepromene Bio, Inc: Current holder of stock options in a privately-held company; Exicure: Current holder of stock options in a privately-held company; January Biotech: Current holder of stock options in a privately-held company; Trillium Therapeutics: Current holder of stock options in a privately-held company; SLAM BIOTHERAPEUTICS, INC: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Zain: Mundi Pharma: Consultancy; Secure Bio: Research Funding, Speakers Bureau; Abbvie: Research Funding, Speakers Bureau; Daiichi Seiko: Consultancy, Research Funding, Speakers Bureau; Verastem: Consultancy; Kyowa Kirin: Consultancy; Seattle Genetics: Consultancy, Research Funding, Speakers Bureau.