Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

Table 4 Summary of clinical trial results of immunomodulator-based therapies

Study	Target disease	No.of patients	Objective response rate	Complete response rate	Progression-free survival	Overall survival	Adverse events or other subjects	Ref.
Randomized phase-II; lenaridomide alone (L) lenaridomide + rituximab (LR)	r/r FL	n = 91, n = 45 (L); n = 46 (LR)	53%, 76%	20%, 39%	Median time to progression: 1.1 yr (at 2.5 yr); 2.0 yr (at 2.5 yr)	Unknown		[34]
Phase-III AUGMENT lenaridomide + R (R2) vs lenaridomide + placebo	r/r FL; r/r MZL	n = 358; n = 180; n = 178	Unknown	Unknown	Median duration: 39.4 mo; 14.1 mo	Unknown	Grade 3 neutropenia of R2 is higher than L	[35]
Phase-IIIb MAGNIFY trial; R maintain after R2 additional lenarimide + rituximab (R2) 18 mo after R2	r/r FL; r/r MZL	n = 393	69% (R2)	40% (R2)	40 mo (similar to AUGMENT trial)	Unknown		[36]
Phase-II GALEN study; lenarimide + obinutuzumab (R2) 18 mo followed by obinutuzumab alone maintenance therapy 1 year	r/r FL	n = 68; evaluable	95% (at 2.6 yr)	38% (n = 33/86)	65% (at 2 yr)	87% (at 2 yr); 81% (n = 70/86); 84% (n = 72/86)		[37]
Phase-III RELEVANCE study, lenaridomide + rituximab (R2) + Rituximab maintenance therapy vs CTx (R-CHOP, BR, or R-CVP)	Untreated advanced FL	n = 1030; R-maintenance, n = 513; CTx, n = 517	Unknown	48%-53%, about the same	3 years-PFS 77%-78%, almost equal to superiority of R2 in F2 frontline not proven	Unknown		[38]
	Untreated advanced FL		Unknown	All 3 groups approximately 90%, about the same	3 yr PFS (5 yr median follow-up); -R 77%, BVR-R 82%, BR-LR 76% (higher in the R- maintenance group than in the R2 group) because of more discontinuations in the R2 group)	3 yr PFS (5 yr median follow-up), BR-R 87%, BVR-R 90%, BR-LR 84%		[39]
Single center phase-II frontline therapy; lenaridomide plus obinutuzumab	Untreated advanced FL	n = 90	98% (after a median follow-up of 22 mo)	92% (after a median follow-up of 22 mo)	2 yr-PFS 96 (after a median follow-up of 22 mo)	Unknown		[40]

“Unknown” means data not shown, unknown information or not reached. r/r: Refractory and relapsed; FL: Follicular lymphoma; MZL: Marginal zone lymphoma; L: Lenaridomide; R: Rituximab; LR: Lenaridomide plus rituximab; R2: Lenaridomide plus rituximab; (R-)CHOP: (Rituximab plus) cyclophosphamide, doxorubicin, vincristine, and prednisolone; BR: Bendamustine plus rituximab; (R-)CVP: (Rituximab plus) cyclophosphamide, vincristine and prednisolone; BR-R: BR induction followed by 2-year rituximab maintenance; BVR-R: BR with bortezomib and rituximab maintenance; BB-LR: BR followed by lenalidomide (1 year) with rituximab maintenance; CTx: Traditional chemotherapy.