Novel Therapies for Aggressive B-Cell Lymphoma

Table 1

Cytotoxic therapies in clinical development for the treatment of aggressive NHL. [B: bendamustine; CLL: chronic lymphocytic leukemia; CR: complete response; CRu: unconfirmed CR; DLBCL: diffuse large B-cell lymphoma; EFS: event-free survival; F: fludarabine; HL: Hodgkin lymphoma; MCL: mantle cell lymphoma; MOA: mechanism of action; mOS: median overall survival; mPFS: median progression-free survival; NHL: non-Hodgkin lymphoma; ORR: overall response rate; OS: overall survival; P: pixantrone; PFS: progression-free survival; PR: partial response; R: rituximab; R-CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone plus rituximab; R/R: relapsed or refractory; SD: stable disease.]

Drug	MOA (target)	Eligibility (and design)	Phase	Randomized	Results
Bendamustine [46]	Alkylating agent	R/R NHL/CLL	Registry	No	ORR: 84.6% in MCL
Bendamustine [45]	Alkylating agent	R/R Lymphoma (±R)	Retrospective analysis	No	MCL: ORR: 67%; 1-year OS: 68%; 1-year PFS: 15% DLBCL: ORR: 31%; 1-year OS: 27%; 1-year PFS: 10%
Bendamustine [42]	Alkylating agent	R/R DLBCL (+R)		No	ORR: 51.6%
Bendamustine [40]	Alkylating agent	R/R aggressive NHL	I	No	B 90 mg/m^2: ORR: 33%;B 120 mg/m^2: ORR: 100%
Bendamustine [41]	Alkylating agent	R/R MCL/NHL	II	No	ORR: 100% in MCL
Bendamustine [44]	Alkylating agent	Previously untreated follicular + indolent + MCL (with R versus R-CHOP)	III	Yes	BR versus R-CHOP: CR: 40.1% versus 30.8% (𝑃=.0323); PFS: 54.8 months versus 34.8 months (𝑃=.0002); OS: no difference
Bendamustine [43]	Alkylating agent	Follicular + indolent + MCL with R versus FR	III	Yes	BR versus FR: CR: 83.5% versus 52.5% (𝑃<.0001); PFS: 30 months versus 11 months (𝑃<.0001); OS: no difference
Pixantrone [49]	Aza-anthracenedione	R/R aggressive NHL (versus other single agents)	III	Yes	𝑃 versus comparator: ORR: 37% versus 14%; CR/CRu: 20% versus 6%; PFS: 4.7 versus 2.6 months; mPFS (𝑃=.007); mOS: 8.1 versus 6.9 months (HR = 0.88, 𝑃=.554)
SB-743921 [51]	Kinesin spindle protein inhibitor	R/R HL or NHL	I/II dose-finding study	No	4 PRs: 3 in HL, 1 in marginal-zone NHL; 1 durable SD (>17 months) in DLBCL
Gemcitabine/oxaliplatin [45]	Chemotherapy	R/R DLBCL with rituximab	II	No	ORR: 43%; CR: 34%; 12-month PFS rate: 29%; 12-month OS rate: 41%
Gemcitabine/oxaliplatin [46]	Chemotherapy	R/R MCL with rituximab		No	CR/CRu: 77%; 2-year PFS rate: 41%; 2-year OS rate: 58%
Gemcitabine/oxaliplatin [47]	Chemotherapy	R/R B-cell NHL with rituximab	II	No	ORR: 83%; CR/CRu: 50%; 2-year EFS: 42%; 2-year OS: 66%
Gemcitabine/oxaliplatin [48]	Chemotherapy	R/R B-cell NHL (transplant ineligible) with R		No	GemOx: ORR: 57%; CR: 30% R-GemOx: ORR: 78%; CR: 50%
Liposomal vincristine [50]	Chemotherapy	R/R NHL	II	No	ORR: 25%; CR/CRu: 5%