LONG‐TERM EFFICACY AND SAFETY OF LENALIDOMIDE MAINTENANCE IN PATIENTS WITH RELAPSED DIFFUSE LARGE B‐CELL LYMPHOMA WHO ARE NOT ELIGIBLE FOR AUTOLOGOUS TRANSPLANTATION (ASCT)

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Background: A multicentre phase II trial showed that lenalidomide (LENA) maintenance was well tolerated and improved outcome in pts with chemosensitive relapse of DLBCL not eligible for or relapsed after ASCT (NCT00799513). However, late side effects and events remained undefined as median follow-up was only 25 months and LENA was ongoing in 41% of pts at time of report. Herein, we report results of the trial after LENA completion in all pts and a median follow-up of 5 years. Methods: HIV-neg pts with de novo or transformed DLBCL responsive to conventional salvage therapy were registered and treated with LENA 25 mg/day for 21/28 days, until lymphoma progression or unacceptable toxicity. A protocol amendment in 2015 allowed physicians to interrupt LENA after a minimum duration of 2 ys. Primary endpoint was 1-yr PFS. Simon's two-stage optimal design was used. To demonstrate a 1-yr PFS improvement from 30% to 50%, 47 pts were needed. Maintenance would be considered effective if ≥19 pts were progression-free at 1 yr. Cell of origin was assessed by NanoString Technology and Hans algorithm. Results: Between 3/2009 and 12/2015, 48 pts were recruited; 46 were assessable (median age 72 ys; range 34-86); 36 pts had de novo DLBCL; most pts had unfavourable features, with an IPI ≥2 in 38 (83%) pts. Salvage therapy before LENA contained high doses of cytarabine or ifosfamide in two-thirds of cases; response at trial registration was complete in 26 pts and partial in 20. LENA was well tolerated after an average of 16 courses/pt (range 3-82); 16 pts received LENA for ≥2 years. 3 pts died of toxicity during maintenance (intestinal infarction, meningitis and sudden death) and 2 died due to myelodysplastic syndrome at 31 and 62 months. LENA was interrupted due to toxicity in other 6 pts, and 25 required dose reduction (transient in 21), mostly due to neutropenia and rash. With the exception of neutropenia, g4 toxicities occurred in <1% of courses. Infections were rare and well controlled with oral antibiotics. After 1 year from registration, 31 pts were progression free, which was significantly higher than the pre-determined efficacy threshold (n≥19). At a median follow-up of 5 years and a median observation period from LENA completion of 35 (8-101) months, 22 pts remain relapse-free, with a 1- and 5-yr PFS of 67 ± 7% and 48 ± 7%, respectively. The duration of response to LENA was longer than response to prior treatment in 30 (65%) pts, and benefit was observed both in de novo and transformed DLBCL, and in GCB and nonGCB subtypes. 27 (59%) pts are alive, with a 1- and 5-yr OS of 80 ± 6% and 58 ± 7%, respectively. Conclusions: These long-term results soundly promote the use of LENA maintenance in pts with chemosensitive relapse of DLBCL not eligible for or failed after ASCT. LENA was well tolerated in this elderly population, even among pts treated for ≥2 ys. Further investigations on immunomodulatory drugs as maintenance in these high-risk pts are warranted. Keywords: diffuse large B-cell lymphoma (DLBCL); elderly; lenalidomide.

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