Dataset Information

Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro.

ABSTRACT: Immunomodulation is an important part of lenalidomide's mode of action. We analyzed the impact of lenalidomide on T cells from patients with multiple myeloma during lenalidomide therapy in vivo and in patients with lenalidomide-refractory disease in vitro Patients enrolled in the German Speaking Myeloma Multicenter Group (GMMG) MM5 trial received a consolidation therapy with two cycles of lenalidomide after autologous stem cell transplantation (ASCT). Half of the study population continued treatment with lenalidomide maintenance therapy for 2 y, while the other patients received lenalidomide maintenance therapy until complete remission. We analyzed 58 patients with (n = 30) or without (n = 28) lenalidomide therapy and 12 patients refractory to lenalidomide with regards to their anti-myeloma-specific T-cell responses displayed by IFNγ, Granzyme B, and Perforin secretion. The immunophenotype of T-cells was investigated by flow cytometry. Significantly, more myeloma-specific T-cell responses were observed in patients during lenalidomide therapy, compared to patients without treatment. Furthermore, we found on T-cells from patients treated with lenalidomide a decreased CD45RA expression, indicating a maturated immunophenotype and a decreased expression of CD57, indicating functional T cells. An improved myeloma-specific T-cell response was observed in 6 out of 12 heavily pretreated patients (refractory to lenalidomide) after in vitro incubation with lenalidomide. Complementary to the results in vivo, lenalidomide decreased CD45RA expression on T cells in vitro.

SUBMITTER: Kramer I

PROVIDER: S-EPMC4910703 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro.

Krämer Isabelle I Engelhardt Melanie M Fichtner Sabrina S Neuber Brigitte B Medenhoff Sergej S Bertsch Uta U Hillengass Jens J Raab Marc-Steffen MS Hose Dirk D Ho Anthony D AD Goldschmidt Hartmut H Hundemer Michael M

Oncoimmunology 20160218 5

Immunomodulation is an important part of lenalidomide's mode of action. We analyzed the impact of lenalidomide on T cells from patients with multiple myeloma during lenalidomide therapy in vivo and in patients with lenalidomide-refractory disease in vitro Patients enrolled in the German Speaking Myeloma Multicenter Group (GMMG) MM5 trial received a consolidation therapy with two cycles of lenalidomide after autologous stem cell transplantation (ASCT). Half of the study population continued treat ...[more]

PMID: 27467960

Similar Datasets

Project description:BackgroundData are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma.MethodsBetween April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15).ResultsThe study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%).ConclusionsLenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).

Dataset Information

Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro.

Publications

Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets