Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study

Abstract

Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1–10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24–80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2–94.7%), 84.5% (CI95: 72.9–98%), and 97.0% (CI95: 91.3–100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma

“…MS-LME exhibited enriched signatures from vascular endothelial cells, cancer-associated fibroblasts, fibroblastic reticular cells, and extracellular matrix, 9 all of which are linked to favorable outcome in DLBCL. 9 For IPI scores of ≥2, GC-LME, IN-LME, and DP-LME categories correlated with inferior prognosis, indicating a necessity for more precise treatment within these patients: GC-LME represented transformed variants of indolent, GC-derived follicular lymphoma, and may be sensitive to lenalidomide plus R-CHOP 9 , 41 ; IN-LME exhibited an enrichment of neutrophils, macrophages, CD8 + T cells, CD8 + T cells with high programmed cell death protein 1 expression, as well as immune-suppressive cytokines. Using Bruton tyrosine kinase inhibitors or other potential agents to modulate the immunosuppressive microenvironment could be potential therapeutic approaches.…”

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials

“…The phase II MC078E study showed that lenalidomide in combination with standard frontline treatment R-CHOP produced high response rates; the ORR in the intent-to-treat population was 97% (32/33), 29 (88%) had CR, and 3 had PR [ 28 ]. In a phase I study of lenalidomide plus R-CHOP, the ORR was 90%, with 81% of untreated, elderly patients with DLBCL achieving CR [ 29 ].…”

2024 Update: Advances in the risk stratification and management of large B‐cell lymphoma

“…A randomized phase II study of 64 patients treated with lenalidomide and R‐CHOP (R2CHOP) revealed an improved 24‐month PFS and OS relative to R‐CHOP among non‐GCB DLBCL 65 . Two single‐arm phase II trials also identified the potential benefits of R2CHOP in elderly patients 66,67 . However, two large phase III RCTs, ROBUST and ECOG‐ACRIN E1412, demonstrated conflicting results.…”

“…65 Two single-arm phase II trials also identified the potential benefits of R2CHOP in elderly patients. 66,67 However, two large phase III RCTs, ROBUST and ECOG-ACRIN E1412, demonstrated conflicting results.…”