Immunochemotherapy plus lenalidomide for high-risk mantle cell lymphoma with measurable residual disease evaluation Journal Article
| Authors: | Epstein-Peterson, Z. D.; Drill, E.; Aypar, U.; Batlevi, C. L.; Caron, P.; Dogan, A.; Drullinsky, P.; Gerecitano, J.; Hamlin, P. A.; Ho, C.; Jacob, A.; Joseph, A.; Laraque, L.; Matasar, M. J.; Moskowitz, A. J.; Moskowitz, C. H.; Mullins, C.; Owens, C.; Salles, G.; Schöder, H.; Straus, D. J.; Younes, A.; Zelenetz, A. D.; Kumar, A. |
| Article Title: | Immunochemotherapy plus lenalidomide for high-risk mantle cell lymphoma with measurable residual disease evaluation |
| Abstract: | 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-of-treatment. 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 TP53wild-type MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL. © 2024 Ferrata Storti Foundation. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; aged; overall survival; gene deletion; lenalidomide; clinical trial; constipation; fatigue; cancer growth; diarrhea; drug efficacy; cytarabine; rituximab; drug megadose; positron emission tomography; follow up; antineoplastic agent; anorexia; cancer immunotherapy; edema; progression free survival; mantle cell lymphoma; multiple cycle treatment; phase 2 clinical trial; anemia; mucosa inflammation; nausea; neuropathy; thrombocytopenia; antineoplastic combined chemotherapy protocols; myalgia; relapse; protein p53; arthralgia; dyspnea; febrile neutropenia; pneumonia; pruritus; rash; immunotherapy; minimal residual disease; sepsis; heterozygosity loss; dry skin; alopecia; cytogenetic analysis; skin infection; lymphoma, mantle-cell; dysgeusia; nose obstruction; hoarseness; single nucleotide polymorphism array; soft tissue infection; high throughput sequencing; intention to treat analysis; human metapneumovirus infection; humans; prognosis; human; male; female; article; cyclophosphamide plus doxorubicin plus prednisolone plus rituximab plus vincristine; measurable residual disease; molecular fingerprinting; peripheral sensory neuropathy; high risk mantle cell lymphoma |
| Journal Title: | Haematologica |
| Volume: | 109 |
| Issue: | 4 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2024-04-01 |
| Start Page: | 1149 |
| End Page: | 1162 |
| Language: | English |
| DOI: | 10.3324/haematol.2023.282898 |
| PUBMED: | 37646671 |
| PROVIDER: | scopus |
| PMCID: | PMC10985438 |
| DOI/URL: | |
| Notes: | Article -- Erratum issued, see DOI: 10.3324/haematol.2024.285845 -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Anita Kumar -- Source: Scopus |
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