Table 1.

Preclinical studies with single-agent lenalidomide in NHL

Study	Cell line	Study findings
Gandhi et al. [11]	Namalwa CSN.70 (Burkitt lymphoma) cells	• Len inhibited proliferation of B-cell lymphoma cells and interfered with Gab1 phosphorylation and adaptor protein complex assembly.
Reddy et al. [14]	Rtx-resistant cell lines created from Raji (Burkitt lymphoma) cells	• Len improved Rtx anti-tumor activity and partially overcame Rtx resistance by augmenting ADCC.
Verhelle et al. [50]	Namalwa (Burkitt lymphoma) and normal CD34+ progenitor cells	• Len plus pomalidomide inhibited proliferation of malignant B cells while expanding population of normal CD34+ progenitor cells.
Zhu et al. [12]	Raji (Burkitt lymphoma), K562 (CLL), PC-3 (prostate cancer), and PBMC cells	• Len plus pomalidomide induced apoptosis through NK cell activation.
Gaidarova et al. [51]	MCL and PBMC (healthy donor) cells	• Len enhanced anti-tumor effects of γδ T-cells against MCL.
Zhang LH et al. [52]	MCL, DLBCL, and FL cells	• Len induced direct anti-proliferative effects against each NHL subtype.
		• Len inhibited high vascular endothelial growth factor levels seen in cell lines.
		• These effects were associated with increased expression of tumor suppressor proteins p21 and SPARC.
Escoubet-Losachet al. [53]	Namalwa (Burkitt lymphoma) and LP-1 (MM) cells	• Len plus pomalidomide induced p21 WAF-1 expression in lymphoma and MM through an LSD1-mediated epigenetic mechanism.
Ramsay et al. [17]	FL, DLBCL, and TmL cells (fresh samples)	• FL cells induced T-cell immunological synapse dysfunction that were repaired with len.

Rtx = rituximab, CLL = chronic lymphocytic leukemia, PBMC = peripheral blood mononuclear cells, MCL = mantle cell lymphoma, FL = follicular lymphoma, MM = multiple myeloma, TmL = transformed lymphoma, DLBCL = diffuse large B cell lymphoma, NHL = non-hodgkin lymphoma, ADCC = antibody-dependent cell-mediated cytotoxicity.