Lenalidomide maintenance significantly improves survival in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT), according to a presentation (abstract 474) at the 58th Annual Meeting of the American Society of Hematology, held December 3–6 in San Diego, California.
Patients with relapsed DLBCL not eligible for ASCT or experiencing relapse after ASCT have a low likelihood of cure. “Single-drug maintenance after salvage therapy may be an option to prolong survival in these poor prognosis patients,” said lead author Andrés J. M. Ferreri, MD, of IRCCS San Raffaele Scientific Institute in Milan, Italy. “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.”
Ferreri and colleagues designed a multicenter, phase II trial addressing lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or experiencing relapse after ASCT. The patients were treated with lenalidomide 25 mg per day for 21 days out of 28, until lymphoma progression or unacceptable toxicity. The primary endpoint was 1-year progression-free survival (PFS).
Of the 48 patients enrolled, 46 patients, median age 72 years, were assessable; 36 patients had de novo DLBCL and 10 patients had transformed DLBCL. All patients were previously treated with anthracycline- and rituximab-based combinations, and 6 patients had ASCT. The median time to progression after the prior therapy was 16 months.
Nearly all of the patients had 2 or more unfavorable features, including an International Prognostic Index score of 2 or more, advanced stage, extranodal disease, and high LDH level.
“At a median follow-up of 25 months, 26 patients were alive and relapse-free and 8 patients were alive after an event,” said Ferreri. Twelve patients died after an event. PFS at 1-year was 70%.
Response duration after lenalidomide was longer than after the prior treatment line in half of patients, and was twice as long in one-third of them, he said. This benefit was seen more in de novo than in transformed patients. There was no difference in efficacy according to cell of origin.
A multivariate analysis found that treatment at first relapse and time to progression of more than 2 years were independently associated with better PFS.
The treatment was well tolerated, and infections were uncommon and well controlled with oral antibiotics, requiring hospitalization in only four episodes. Lenalidomide dose reduction was indicated in 23 patients and was transient in 19 patients. Eight of the nine patients with serious adverse events recovered, and six continued on lenalidomide.
In conclusion, Ferreri said: “With the limitations of a non-randomized design, this trial supports the use of lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or experiencing relapse after ASCT. Lenalidomide maintenance was feasible in this elderly population. Unexpected toxicity was not observed in HBV/HCV-positive patients or among previously transplanted patients.”
He suggested that lenalidomide may overcome the negative effect the ABC DLBCL phenotype has on outcomes.
“These results warrant further investigation of immunomodulatory drugs as maintenance in high-risk patients with DLBCL,” said Ferreri.