Immunochemotherapy plus lenalidomide for high-risk mantle cell lymphoma with measurable residual disease evaluation

oleh: Zachary D. Epstein-Peterson, Esther Drill, Umut Aypar, Connie Lee Batlevi, Philip Caron, Ahmet Dogan, Pamela Drullinsky, John Gerecitano, Paul A. Hamlin, Caleb Ho, Allison Jacob, Ashlee Joseph, Leana Laraque, Matthew J. Matasar, Alison J. Moskowitz, Craig H. Moskowitz, Chelsea Mullins, Colette Owens, Gilles Salles, Heiko Schöder, David J. Straus, Anas Younes, Andrew D. Zelenetz, Anita Kumar

Format: Article
Diterbitkan: Ferrata Storti Foundation 2023-08-01

Deskripsi

Chemoimmunotherapy followed by consolidative high-dose therapy with autologous stem cell rescue was a standard upfront treatment for fit patients with mantle cell lymphoma (MCL) in first remission; however, treatment paradigms are evolving in the era of novel therapies. Lenalidomide is an immunomodulatory agent with known efficacy in treating MCL. We conducted a single-center, investigator-initiated, phase II study of immunochemotherapy incorporating lenalidomide, without autologous stem cell transplant consolidation, enriching for patients with high-risk MCL (clinicaltrials gov. Identifier: NCT02633137). Patients received four cycles of lenalidomide-R-CHOP, two cycles of R-HiDAC, and six cycles of R-lenalidomide. The primary endpoint was rate of 3-year progression-free survival. We measured measurable residual disease (MRD) using a next-generation sequencing-based assay after each phase of treatment and at 6 months following end-oftreatment. We enrolled 49 patients of which 47 were response evaluable. By intent-to-treat, rates of overall and complete response were equivalent at 88% (43/49), one patient with stable disease, and two patients had disease progression during study; 3-year progression-free survival was 63% (primary endpoint not met) and differed by TP53 status (78% wild-type vs. 38% ALT; P=0.043). MRD status was prognostic and predicted long-term outcomes following R-HiDAC and at 6 months following end-of-treatment. In a high-dose therapy-sparing, intensive approach, we achieved favorable outcomes in TP53- wild-type MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL.