Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

Table 7 Summary of Clinical Trial Results of phosphoinositide 3 kinase inhibitors

Study	Target disease	No. of patients	Objective response rate	Complete response rate	Progression-free survival	Overall survival	Adverse events or others	Ref.
Indelalisib, phase-II DELTA trial	r/r FL	n = 55	73% (highest ever reported)	Unknown	72% disease-free after 12 mo	80% alive after 12 months	54% of G3 or higher	[65]
Indelalisib phase-II open-labeled trial	r/r NHL (including FL), median of 4 lines prior therapy	iNHL, n = 72; FL, n = 42)	57%	Unknown	11 mo	Unknown	54% of G3 or higher	[66]
Duvelisib	iNHL (including FL)	n = 187	70% good	Unknown	Unknown	Unknown	63% of G3 or higher	[63,69]
Conpalisib, phase-II CHRONOS-1 trial	r/r FL, median 3-lines of prior therapy	n = 142	59%	12%	11 mo (median)	43 mo (median)	G3 84%, 6 cases of G5 events	[70,71]
Umbralisib, phase-II trial	iNHL (including FL) median 3-lines or more of prior therapy	n = 208 (FL = 117)	47.1% of (after a median follow-up of 27.7 mo)	Unknown	10.6 mo (median PFS)	Unknown		[74]
Parsaclisib, phase-Ib, CITADEL-111 trial	Japanease: r/r FL; r/r MZL; r/r DLBCL	n = 9; n = 2; n = 6	9 cases (= 100%); 2 cases (= 100%); 1 case (= 16.7%)	22.2% (n = 2/9); 100% (n = 2/2); 16.7% (n = 1/6)	Unknown	High incidence of adverse events-need to carefully select target patients	Neutropenia above G3 interrupted in 58.8% and reduced in 29.4%	[75]
Parsaclisib, phase-I/II (phase-II trial is ongoing)	r/r B-NHL	n = 72	71% (r/r FL); 78% (r/r MZL); 67% (r/r MCL); 30% (r/r DLBCL)	Unknown	Unknown	Unknown	G3/4 neutropenia occurred in 19%	[76]
Zandelisib (ME-401), phase-I trial	Japanese, r/r iNHL	n = 9	100% (n = 9/9)	22% (n = 2/9), median duration of response 7.9 mo; median time to response 1.9 mo		Unknown	G3 or higher neutropenia 6/9 (55.6%) diarrhea 3/9 (33.3%) and many events	[77]
Zandelisib alone vs zandelisib + rituximab	r/r FL	n = 12	92% (n = 11/12) in the 60 mg group; 83% (n = 5/6) in the 180 mg group	Unknown	Unknown	Unknown		[78]
	r/r iNHL, median 3-lines of prior therapy	n = 30 + BR (n = 19) vs + R-CHOP (n = 11)	90% (+ BR) vs 100% (+ R-CHOP)	Unknown	Unknown	Unknown	G3 or higher, high rate of 70% (BR), 91% (R-CHOP)	[79]

“Unknown” means data not shown, unknown information or not reached. r/r: Refractory and relapsed; FL: Follicular Lymphoma; B-NHL: B-cell non-Hodgkin lymphoma; (i)NHL: (Indolent) non-Hodgkin lymphoma; DLBCL: Diffuse large B-cell lymphoma; MZL: Marginal zone lymphoma; MCL: Mantle cell lymphoma.