The Lancet Haematology published in February 2017 the results of a phase II, open-label, multicenter trial by Andrés José Maria Ferreri, from the Unit of Lymphoid Malignancies, Ospedale San Raffaele, Milan, Italy, and colleagues. The study recruited 48 chemosensitive relapsed DLBCL patients who were not eligible for Autologous Stem Cell Transplant (ASCT) or who relapsed following ASCT, and investigated the efficacy and safety of treating these patients with maintenance lenalidomide.
- 48 pts recruited, 2 ineligible due to unconfirmed DLBCL diagnosis
- Over 70yrs = 28 pts (61%), de novo DLBCL = 36 pts (78%), transformed DLBCL= 10 pts (22%), first relapse = 33 pts (72%)
- 25mg lenalidomide daily on D1–21 of a 28D cycle until progression or intolerable toxicity (amendment allowed discontinuation after 24 courses)
- Lenalidomide treatment started within two months of salvage therapy conclusion with patients achieving a CR or PR
- Salvage therapy was investigator choice (no difference in response was observed)
- Mean 12 courses per patient (3–41)
- Median follow-up 25 months:
- One-year PFS = 70% (95% CI, 57–83)
- One-year OS = 81% (95% CI, 70–92)
- Three-year OS = 71% (57–85)
- One-year PFS similar in both GCB-DLBCL and non-GCB-DLBCL (64% vs 67%, P = 0.67)
- Median follow-up 25 months:
- SAEs = 10 events in 9 pts (febrile neutropenia = 4, diarrhea = 2, melena = 1, stroke = 1, vomiting = 1, intestinal infarction = 1 who died
- Dose reduction in 23 pts due to AEs, reduction was temporary in 19 pts
- Interruptions = 11 pts, half after one year on maintenance, half related to grade 2 toxicities
- Dose reduction did not result in significantly lower PFS (P = 0.46)
The authors identified the limitations of their study being that it was conducted in a small non-randomized population and that there was no consistency in salvage therapy approach. However, the authors also state that this is the first trial to show a positive result of maintenance therapy in relapsed DLBCL, resulting in extended PFS with a good safety profile. In conclusion, the authors state that maintenance lenalidomide was shown to be tolerated and effective in an elderly DLBCL population and should be investigated further.
- Ferreri A.J.M. et al. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. The Lancet Haematology. 2017 Feb 16. DOI: 1016/S2352-3026(17)30016-9. [Epub ahead of print: 2017 Feb 16].
Background. Patients with relapsed diffuse large B-cell lymphoma (DLBCL) not eligible for autologous stem cell transplantation (ASCT) or having relapse after ASCT have a low likelihood of cure. Single-drug maintenance after salvage therapy might be an attractive strategy to prolong survival in these patients. Lenalidomide is a suitable candidate for long-lasting maintenance as it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile. We designed a study to investigate safety and efficacy of lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or having relapse after ASCT. Methods. In this open-label, single group, multicentre phase 2 trial, we recruited HIV-negative adults with de novo or transformed DLBCL and relapsed disease responsive to conventional rituximab-containing salvage therapy from 12 oncology-haematology centres in Italy. All patients were given oral lenalidomide 25 mg per day for 21 of 28 days until lymphoma progression or unacceptable toxicity (severely compromises organ function, quality of life, or both). Primary endpoint was 1-year progression-free survival. The estimated sample size was 47 patients; maintenance was deemed efficacious if at least 19 patients were progression-free survivors at 1 year. All enrolled patients were included in primary analyses, with the exception of patients who post-hoc objectively did not meet the eligibility criteria (modified intention-to-treat). This study is registered with clinicaltrials.gov registry, number NCT00799513. Findings. Between March 24, 2009, and Dec 22, 2015, we recruited 48 patients. 46 of 48 enrolled patients were assessable (two patients had unconfirmed diagnoses). 36 (78%) of 46 patients had de novo DLBCL and ten (22%) of 46 patients had transformed DLBCL. At a median follow-up of 25 months (IQR 12–56), 556 lenalidomide courses had been delivered, with an average mean of 12 courses (range 3–41) per patient; 19 patients were still in treatment at a median follow-up of 25 months. Lenalidomide was well tolerated; with the exception of neutropenia, grade 3–4 toxicities were uncommon. We recorded ten severe adverse events in nine patients due to febrile neutropenia (n=4), diarrhoea (n=2), melena, stroke, vomiting, and intestinal infarction; all but one patient recovered, and six of these patients continued with lenalidomide treatment. The exception was the only death due to toxicity (intestinal infarction). At 1 year from trial registration, 28 patients were progression free, which was much higher than the predetermined efficacy threshold. During the whole observation period, 21 events occurred: progressive lymphoma in 19 patients, death due to toxicity in one, death while off therapy in one, 1-year progression-free survival was 70% (95% CI 57–83). Interpretation. With the limitations of a non-randomised design, this trial supports the use of lenalidomide maintenance in patients with chemo-sensitive relapse of DLBCL who are not eligible for ASCT or who had relapse after ASCT. These results warrant further investigation of immunomodulatory drugs as maintenance in high-risk patients with DLBCL.