Single-drug maintenance after salvage therapy could prolong survival of pts with rDLBCL not eligible to ASCT. LEN could be an excellent candidate as it is an oral agent, active against DLBCL, with excellent safety profile. Herein, we report results of a multicentre phase II trial addressing LEN maintenance (mLEN) in pts with chemosensitive rDLBCL.
HIV-negative pts with DLBCL relapsed after R-CHOP or similar and responsive to salvage therapy were registered and treated with LEN 25 mg/day for 21 days out of 28 until lymphoma failure or unacceptable toxicity. Primary endpoint was the 1-year PFS. Estimated sample size (Simon's two-stage optimal design; type I error 5%, power 80%, P0 30%, P1 50%) was 47 pts; mLEN would be considered effective if ≥ 19 pts will be progression-free survivors at 1 year. The prognostic role of cell of origin, assessed by NanoString and Hans algorithm, was investigated.
46 of 48 enrolled pts were assessable (median age 72 years; 34-86); 26 pts started mLEN in CR and 20 in PR after salvage therapy. 639 LEN courses were delivered, with an average of 14 courses/pt (3-53). LEN was well tolerated: with the exception of neutropenia, grade 3-4 toxicities were uncommon (≤3% of courses). LEN dose reduction was indicated in 25 pts. Three pts died of toxicity: intestinal infarction, meningitis, unknown cause; 2 pts developed a second cancer. The pre-determined efficacy threshold (n ≥ 19) was largely achieved: 32 pts were progression free at 1 year from registration. At a median follow-up of 38 (14-95) months, 23 events occurred: PD in 19 pts, death of toxicity in 3, death while off therapy in 1, with a 1-yr PFS of 70% (95%CI=59-81). The benefit of mLEN was observed both in pts with de novo or transformed DLBCL, and both in GCB- or nonGCB-DLBCL. 29 (63%) pts are alive, with a 3-yr OS of 64%.
With the limitations of a non-randomized design, this trial soundly promotes the use of mLEN in pts with chemosensitive rDLBCL not eligible for ASCT or experiencing relapse after ASCT. These results warrant further investigation of immunomodulatory drugs as maintenance in these high-risk pts.
Clinical trial identification
Legal entity responsible for the study
IRCCS San Raffaele
All authors have declared no conflicts of interest.