Table 1.

Novel treatments in clinical trials, including MZL patients with relapsed/refractory non-Hodgkin’s lymphoma or relapsed B-cell lymphoma^2,3,30,32,33

Pathway	Drug	Target	N evaluable MZL patients*	Overall response rate	Complete response rate	Duration of response months (months)	Limiting toxicity
PI3K/AKT/mTOR	Everolimus	mTOR	24 MZL (16 MALT; 4 NMZL)	28%	4%	—	Hematologic (46%, G3/4), interstitial pneumonia (4%)
	Idelalisib	PI3K-d	15 MZL	57%	6%	18.4	Neutropenia (27%, G3/4), aminotransferase elevations (13%, G3/4), diarrhea (13%, G3/4), pneumonia (7%, G3/4)
	Copanlisib	PI3K-d and PI3K-α	23 MZL/141	69.6%	8.7%	Not reached	hypertension (49%, G3/4), neutropenia (30%, G3/4), hyperglycemia (30%, G3/4), anemia (15%, G3/4)
BcR	Ibrutinib	BTK	63 MZL	48%	3%	Not reached at a median follow-up at 19.4 (95% CI, 17.6-22.3)	Pneumonia (8%, G3/4)
							Anemia 1 (4%, G3/4)
							Diarrhea (5%, G3/4)
Apoptosis	Venetoclax	BCL2	3 MZL/106	67%	0%	2.3 and 23.6	Neutropenia (8% to 14%,† G3/4), anemia (19%), thrombocytopenia (8% to 32%†), febrile neutropenia (2%†)
Microenvironment	Lenalidomide	Immune modulator	30 MZL	89%	67%	Median PFS 53.8 (95% CI, 50.6 to NA)	Neutropenia (35%); muscle pain (9%); rash (7%); cough, dyspnea, or other pulmonary symptoms (5%); thrombosis (5%); thrombocytopenia (4%)
Proteasome	Bortezomib	Proteasome
	Rituximab + bortezomib 1.3 mg/m2 twice weekly or 1.6 mg/m2 weekly		9 r/r MZL and 70 FL	49%	14%	Median TTP 7.0	Thrombocytopenia (10%, G3/4)
				43%	10%	Median TTP 10.0	Neuropathy (10%, G3/4)
							Diarrhea (15%, G3/4)

BTK = Bruton’s tyrosine kinase; CR = complete remission; G = grade; NA, not applicable; ORR = overall response rate; PI3K = phosphoinositol 3 kinase; r/r, relapse/refractory; TTP, time to progression.

^*The number of patients with SMZL and NMZL not systematically available.

^†From all doses (400, 600, 900, or 1200 mg).