Table 1 Status of current clinical... | American Society of Hematology

Table 1

Status of current clinical development of novel, targeted drugs in CLL

Class	Agent	Target	Route	Current stage of clinical development	Comments, specific side effects	Response rate in relapsed, refractory CLL as a single agent
Class	Agent	Target	Route	Current stage of clinical development	Comments, specific side effects	N	CR	PR	ORR
Antibodies	Obinutuzumab (GA101)⁶³	CD20	IV	Phase 3	Cytokine release at first infusion	13	8%	54%	62%
	Dacetuzumab⁹⁵	CD40	IV	Phase 1	Some disease stabilizations	12	0%	0%	0%
	Lucatumumab⁹⁶	CD40	IV	Phase 2	Amylase, lipase increase	26	0%	4%	4%
Immune gene therapy	ISF35 (Adenovirus-CD154)⁹⁷	CD40	Intra-nodal	Phase 1	Mild flu-like symptoms	15	0%	20%	20%
	CART19 (engineered T cells)⁹¹	CD19	IV	Phase 1/2	TLS, cytokine release syndrome	9	44%	22%	66%
Small immune-pharmaceutical	TRU-016⁹⁸	CD37	IV	Phase 2	Neutropenia, infections, diarrhea, fatigue	17	0%	17%	17%
Bcl-2 antagonists	ABT-263 (Navitoclax)⁷³	Bcl-2 and Bcl-X(L)	PO	Phase 1/2a	Thrombocytopenia	26	0%	35%	35%
	Obatoclax⁹⁹	Pan-Bcl-2 antagonist	IV	Phase 2	Neurologic, infusion-related symptoms (somnolence, euphoria, ataxia)	26	0%	4%	4%
	ABT-199⁷⁵	Bcl-2	PO	Phase 3	TLS, neutropenia	56	13%	72%	85%
Tyrosine kinase inhibitors	Fostamatinib¹⁰⁰	Syk	PO	Phase 1/2	Diarrhea, fatigue, cytopenia, hypertension, nausa	11	0%	55%	55%
	ldelalisib (CAL-101)⁶⁷	PI3K p1108	PO	Phase 3	Abnormal liver function, pneumonia	54	4%	52%	56%
	lbrutinib (PCI-32765)⁵⁸	Bruton tyrosine kinase	PO	Phase 3	Diarrhea	85	2%	68%	71%
	Dasatinib¹⁰¹	Abl and Src family kinases	PO	Phase 2	Pleural effusion	15	0%	20% (60%)†	20% (60%)†
Cyclin-dependent kinase inhibitors	Flavopiridol¹⁰²	CDK	IV	Phase 2	TLS	52	0%	40%	40%
	Dinaciclib¹⁰³	CDK 1,2,5,9	IV	Phase 1	TLS, anemia, neutropenia, thrombocytopenia, hyperglycemia, hypocalcemia, diarrhea, hypokalemia, increased AST/ALT, fatigue.	23	0%	35%	35%
	SNS-032¹⁰⁴	CDK 2,7,9	IV	Phase 1	TLS, myelosuppression; limited antitumor activity	19	0%	0%	0%
mTOR inhibitors	Everolimus^88,89	mTOR	PO	Phase 1/2	Immunosuppression, severe infections	22	0%	18% 14%	18% 14%
mTOR inhibitors	Everolimus^88,89	mTOR	PO	Phase 1/2	Immunosuppression, severe infections	7	0%
Immunomodulatory drugs	Lenalidomide⁸⁰	Multiple	PO	Phase 3	Immunosuppression, myelotoxicity, tumor flare, thromboembolic events	29*	7%	27%	34%

Class	Agent	Target	Route	Current stage of clinical development	Comments, specific side effects	Response rate in relapsed, refractory CLL as a single agent
Class	Agent	Target	Route	Current stage of clinical development	Comments, specific side effects	N	CR	PR	ORR
Antibodies	Obinutuzumab (GA101)⁶³	CD20	IV	Phase 3	Cytokine release at first infusion	13	8%	54%	62%
	Dacetuzumab⁹⁵	CD40	IV	Phase 1	Some disease stabilizations	12	0%	0%	0%
	Lucatumumab⁹⁶	CD40	IV	Phase 2	Amylase, lipase increase	26	0%	4%	4%
Immune gene therapy	ISF35 (Adenovirus-CD154)⁹⁷	CD40	Intra-nodal	Phase 1	Mild flu-like symptoms	15	0%	20%	20%
	CART19 (engineered T cells)⁹¹	CD19	IV	Phase 1/2	TLS, cytokine release syndrome	9	44%	22%	66%
Small immune-pharmaceutical	TRU-016⁹⁸	CD37	IV	Phase 2	Neutropenia, infections, diarrhea, fatigue	17	0%	17%	17%
Bcl-2 antagonists	ABT-263 (Navitoclax)⁷³	Bcl-2 and Bcl-X(L)	PO	Phase 1/2a	Thrombocytopenia	26	0%	35%	35%
	Obatoclax⁹⁹	Pan-Bcl-2 antagonist	IV	Phase 2	Neurologic, infusion-related symptoms (somnolence, euphoria, ataxia)	26	0%	4%	4%
	ABT-199⁷⁵	Bcl-2	PO	Phase 3	TLS, neutropenia	56	13%	72%	85%
Tyrosine kinase inhibitors	Fostamatinib¹⁰⁰	Syk	PO	Phase 1/2	Diarrhea, fatigue, cytopenia, hypertension, nausa	11	0%	55%	55%
	ldelalisib (CAL-101)⁶⁷	PI3K p1108	PO	Phase 3	Abnormal liver function, pneumonia	54	4%	52%	56%
	lbrutinib (PCI-32765)⁵⁸	Bruton tyrosine kinase	PO	Phase 3	Diarrhea	85	2%	68%	71%
	Dasatinib¹⁰¹	Abl and Src family kinases	PO	Phase 2	Pleural effusion	15	0%	20% (60%)†	20% (60%)†
Cyclin-dependent kinase inhibitors	Flavopiridol¹⁰²	CDK	IV	Phase 2	TLS	52	0%	40%	40%
	Dinaciclib¹⁰³	CDK 1,2,5,9	IV	Phase 1	TLS, anemia, neutropenia, thrombocytopenia, hyperglycemia, hypocalcemia, diarrhea, hypokalemia, increased AST/ALT, fatigue.	23	0%	35%	35%
	SNS-032¹⁰⁴	CDK 2,7,9	IV	Phase 1	TLS, myelosuppression; limited antitumor activity	19	0%	0%	0%
mTOR inhibitors	Everolimus^88,89	mTOR	PO	Phase 1/2	Immunosuppression, severe infections	22	0%	18% 14%	18% 14%
mTOR inhibitors	Everolimus^88,89	mTOR	PO	Phase 1/2	Immunosuppression, severe infections	7	0%
Immunomodulatory drugs	Lenalidomide⁸⁰	Multiple	PO	Phase 3	Immunosuppression, myelotoxicity, tumor flare, thromboembolic events	29*	7%	27%	34%

PO indicates per ora (orally); TLS, tumor lysis syndrome.

Analysis included only fludarabine-refractory patients.

†

60% showed nodal responses without a 50% reduction of lymphocyte counts.

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