A study published in “The Lancet Haematology” depicted that lenalidomide after autologous haematopoetic stem-cell transplantation improves progression-free survival in individuals with mantle cell lymphoma (cancer of white blood cells).
Researchers undertook this phase III, open-label, randomized, multicentre trial (Fondazione Italiana Linfomi) to determine if post-autologous haematopoetic stem-cell transplantation maintenance with lenalidomide leads to improvement in progression-free survival. Eligible participants had mantle cell lymphoma and had evidence of cyclin D1 overexpression or translocation.
Following an optional prephase with steroids and vincristine, individuals were administered three courses of R-CHOP (21-day cycle, intravenous 375 mg/m2 rituximab on the first day; intravenous 50 mg/m2 doxorubicin, 1·4 mg/m2 vincristine, and 750 mg/m2 cyclophosphamide on the second day; oral 100 mg/m2 prednisone on day two-six).
Individuals were then given one cycle of high-dose CTX (intravenous 4 g/m2 cyclophosphamide on the first day, intravenous 375 mg/m2 rituximab on the fourth day). Following restaging, participants were given two cycles of R-HD-cytarabine (high-dose intravenous 2 g/m2 cytarabine every 12 hours on days one-three, intravenous 375 mg/m2 rituximab on days 4 and 10).
Subjects with remission (complete or partial) progressed to autologous haematopoetic stem-cell transplantation. The responding subjects (complete or partial remission) with haematological recovery were randomized to either: (I) Group I: Received 24 courses of oral lenalidomide maintenance for 24 months, (ii) Group II: Observation group
Progression-free survival was the major outcome ascertained. Participants were randomly assigned either to the lenalidomide maintenance group (n=104) or observation group (n=104). Notably, 11% (11/104) of subjects allocated to lenalidomide did not initiate treatment. At the median follow-up of 38 months after randomization, the three-year progression-free survival was higher in the lenalidomide arm vs. observation arm.
Overall, 39% (41/104) patients discontinued lenalidomide for reasons including mortality or disease advancement. Treatment-related deaths, the percentage of patients with grade 3-4 hematological and non-hematological adverse events, and serious adverse events are shown in the table below:
|Lenalidomide group||Observation group|
|Three-year progression-free survival||80%||64%|
|Treatment-related deaths||2% (2/93)||1% (1/101)|
|Grade 3-4 hematological adverse events||63% (59/93)||12% (12/101)|
|Grade 3-4 non-hematological adverse events||31% (29/93)||8% (8/101)|
|Serious adverse events||24% (22/93)||5% (5/101)|
Table 1: Comparison between lenalidomide and observation group
The most commonly noted severe adverse events were pneumonia and other infections. Regardless of non-negligible toxicity, lenalidomide after autologous haematopoetic stem-cell transplantation was found to enhance the progression-free survival in individuals suffering from lymphoma, thus emphasizing the role of maintenance in lymphoma.
|Source||The Lancet Haematology|
|Link:||https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30358-6/fulltext [Last accessed on: 25 May, 2021]|
|Original title of the article||Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial|
|Authors:||Marco Ladetto et al.|