{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T22:57:19Z","timestamp":1768604239293,"version":"3.49.0"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI Cancer Center Support","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Immune evasion through inhibition of effector T cells is a key survival mechanism of lymphoma cells. We hypothesized that reinstating effector T cell activity through concurrent inhibition of the PD1\/PD-L1 axis and of Treg activity will result in a synergistic anti-tumor effect with an acceptable toxicity profile. Methods: Phase I multi-institutional NCI-ETCTN trial aimed to evaluate the safety and tolerability of the combination of mogamulizumab and pembrolizumab in relapsed or refractory non-Hodgkin lymphoma. The study used a 3 + 3 design. Treatment consisted of mogamulizumab 1 mg\/kg on days 1, 8, and 15 of cycle 1, followed by 1.5 mg\/kg on day 1 of each subsequent 21-day cycle in combination with pembrolizumab 200 mg on day 1 of each cycle. A de-escalation level was defined as a 50% reduction in the dose of mogamulizumab (registered in clinicaltrials.gov NCT03309878). Results: The study was discontinued early, after treating seven patients (two angioimmunoblastic T cell lymphoma, four transformed follicular lymphoma, and one diffuse large B cell lymphoma of germinal center subtype) for concerns of futility and non-tolerability. Only two patients completed the first two cycles of treatment. Three patients presented with an early progression and three withdrew consent in the setting of general deterioration with clinically suspected progression. All six patients expired shortly after withdrawal from the study. The remaining patient experienced stress cardiomyopathy during the third cycle and was taken off the study. Discussion: In striking difference to the observation in solid malignancies, the combination of mogamulizumab with pembrolizumab was associated with low tolerability and suspected hyper-progression in patients with lymphoma.<\/jats:p>","DOI":"10.3390\/cancers18020284","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:39:37Z","timestamp":1768563577000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase I Study of Mogamulizumab in Combination with Pembrolizumab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma\u2014A National Cancer Institute Experimental Therapeutics Clinical Trials Network (NCI-ETCTN) Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-289X","authenticated-orcid":false,"given":"Erel","family":"Joffe","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"},{"name":"School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Kumar","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Tuscano","sequence":"additional","affiliation":[{"name":"University of California Davis Comprehensive Cancer Center, Sacramento, CA 95838, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison J.","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette","family":"Owens","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariela","family":"Noy","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-9156","authenticated-orcid":false,"given":"Maria Lia","family":"Palomba","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Zelenetz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Ni","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elad","family":"Sharon","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD 20850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-1298","authenticated-orcid":false,"given":"Santosha","family":"Vardhana","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, Department of Medicine, Lymphoma Service, New York, NY 10065, USA"},{"name":"Weill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3324\/haematol.2019.243626","article-title":"Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell 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