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

Figures & data

Figure 1. Lenalidomide therapy enhances the antigen-specific immune response of CD8⁺ T cells from patients with multiple myeloma. The number of patients with specific or no specific immune response treated with or without lenalidomide is shown.

Figure 2. Impact of lenalidomide therapy on the expression of T-cell markers. Shown is the expression of (A) CD45RA, (B) CD28, (C) CCR7 and (D) CD279 (E) CD38, (F) CD154, (G) HLA-DR, (H) CD57 on CD8⁺ T cells (in % of all CD8⁺ T cells) from patients with MM treated with or without lenalidomide, analyzed by flow cytometry.

Figure 3. Impact of lenalidomide therapy on the CD4⁺CD127^dimCD25^high Foxp3⁺regulatory T-cell compartment. Shown is the percentage of CD4⁺CD127^dimCD25^highFoxp3⁺regulatory T cell of all CD4⁺ T cells in patients with MM treated with or without lenalidomide, analyzed by flow cytometry.

Figure 4. Representative EliSpot-analysis. The figure shows a representative EliSpot analysis from a lenalidomide refractory patient with T cells demonstrating an enhanced antigen-specific T-cell response against the myeloma antigen HM1.24 after in vitro incubation with lenalidomide.

Table 1. Patient characteristics (newly diagnosed patients).

Characteristics
Total patients, n (%)	Number of patients, n (%)
Gender, n (%)	58 (100%)
Female	24 (41.4%)
Male	34 (58.6%)
Median age at begin of induction, years (range)	56.4 (35.0–71.8)
Type, n (%)
IgG Kappa	21 (36.2%)
IgG Lambda	13 (22.4%)
IgA Kappa	9 (15.5%)
IgA Lambda	4 (6.9%)
IgD Lambda	1 (1.7%)
BJP Kappa	7 (12.1%)
BJP Lambda	3 (5.2%)
Median initial β-2 microglobulin, mg/L (range)	3.0 (1.6–226.0)
ISS at first diagnosis, n (%)
I	34 (58.6%)
II	14 (24.1%)
III	9 (15.5%)
n.a.	1 (1.7%)
CRAB symptoms at first diagnosis, n (%)
Hypercalcemia alone	0 (0%)
Renal insufficiency	2 (3.4%)
Anemia	7 (12.1%)
Bone lesions	39 (67.2%)
Hypercalcemia and bone lesions	1 (1.7%)
Hypercalcemia, renal insufficiency and bone lesions	1 (1.7%)
Renal insufficiency, anemia and bone lesions	2 (3.4%)
Anemia and lytic bone lesions
High-risk cytogenetics, n (%)
del17p13	6 (10.3%)
t(4;14)	4 (6.9%)
dupl 1q21	8 (13.8%)
del17p13 and t(4;14)	3 (5.2%)
Induction therapy, n (%)	1 (1.7%)
3xPAd	25 (43.1%)
3xVCD	33 (56.9%)
Number of autologous stem cell transplantation, n (%)
0	1 (1.7%)
1	35 (60.3%)
2	22 (37.9%)
Remission status before consolidation therapy, n (%)
SD/MR	1 (1.7%)
PR/VGPR	24 (41.4%)
nCR/CR	33 (56.9%)
Immune response, n (%)
Positive	19 (32.8%)
Negative	15 (25.9%)
N.A.	24 (41.4%)
Treatment with lenalidomide, n (%)
no	28 (48.3%)
yes	30 (51.7%)
Median cumulative dose of lenalidomide, mg (range)	2310 (525–8610)

BJP, Bence–Jones protein; ISS, International Staging System; n.a., not available; del, deletion; t, translocation; dupl, duplication; SD, stable disease; MR, minor response; PR, partial response; VGPR, very good partial response; nCR, near complete remission; CR, complete remission; mg, milligram.

Table 2. Patient characteristics (patients with lenalidomide-refractory multiple myeloma).

Characteristics
Total patients, n (%)	Number of patients, n (%)
Gender, n (%)	12 (100%)
Female	6 (50%)
Male	6 (50%)
Median age at time of sampling, years (range)	67.6 (47–85)
Median number of pretreatment regimens, n (range)	8 (7–11)
Type, n (%)
IgG Kappa	3 (24.9%)
IgG Lambda	1 (8.3%)
IgA Kappa	2 (16.6%)
IgA Lambda	2 (16.6%)
IgD Kappa	1 (8.3%)
BJP Lambda	1 (8.3%)
BJP Kappa	1 (8.3%)
Hyposec.	1 (8.3%)
ISS at time of sampling, n (%)
I	0 (0%)
II	1 (8.3%)
III	11 (91.7%)
Previous chemotherapy regiments (per patient), range	6.4 (4–9)
Status at time of sampling, n (%)
SD/MR	1 (8.3%)
PR/VGPR	1 (8.3%)
nCR/CR	1 (8.3%)
PD	9 (75.1%)
Immune response, n (%)
Positive	6 (50%)
Negative	6 (50%)

BJP, Bence–Jones protein; ISS, International Staging System; SD, stable disease; MR, minor response; PR, partial response; VGPR, very good partial response; nCR, near complete remission; CR, complete remission; PD, progressive disease.

Figure 5. Impact of lenalidomide in vitro in patients with refractory multiple myeloma on the expression of T-cell markers. The plot shows the expression of CD45RA on CD8⁺ T-cells (in % of all CD8⁺ T cells) from patients with refractory MM analyzed by flow cytometry.