Advances in the treatment of monoclonal gammopaties: The emerging role of targeted therapy in plasma cell dyscrasias

Figures & data

Figure 1 Mechanisms of action of novel agents. Novel molecules can: I) directly inhibit clonal cells; II) inhibit angiogensis; III) inhibit tumor cell adhesion to bone marrow stromal cells (BMSCs); IV) decrease cytokine production from BMSCs; V) increase host anti-tumor immunity.

Table 1 Ongoing clinical trials using thalidomide-based regimens in MM and WM (www.clinicaltrials.gov)

Treatment regimen	Disease	Phase	Endpoints
Thal+Bort	MM/refractory	I	Toxicities
Thal+Dex vs Doxil+Thal+Dex	MM/newly diagnosed	III	ORR, OS
Thal+Clarithromycin+Len+ Dex	MM/relapsed refractory	II	Safety, efficacy
Thal+Doxorubicin+Dex	MM/untreated stage II/III	II	ORR, safety, toxicity
Thal+/-Lenal+Dex	MM	III	ORR, toxicity
Thal+Bort	MM/newly diagnosed stage II/III	II	Tumor response, mobilization/collection stem cells, incidence/severity of neuropathy
Thal+Doxil+Bort	MM/untreated stage I/II/III	II	ORR, TTP
Thal+AsO3+ascorbic acid+ Dex	MM/relapsed, refractory	I	Toxicity, safety, tolerability
Thal+Oblimersen+Dex	MM/relapsed, refractory	II	ORR
Thal+Bort+CTX+Dex	MM/untreated	II	ORR, safety, tolerability
Thal+Riuximab	WM	II	ORR, TTF, toxicity

Abbreviations: Thal, thalidomide; Bort, Bortezomib; Doxil, liposomal doxorubicine; Len, lenalidomide; Dex, dexamethasone; CTX, cyclophosphamide; AsO₃, arsenic trioxide; Mel, melphalan; Pdn, prednisone; ORR, overall response rate; OS, overall response; TTP, time to progression; PFS, progression-free survival; TTF, time to treatment failure.

Table 2 Ongoing clinical trials using lenalidomide-based regimens in MM and WM (www.clinicaltrials.gov)

Treatment regimen	Disease	Phase	Endpoints
Len+Doxorubicine+Dex	MM/relapsed, refractory	I/II	Safety, efficacy, ORR
Len+Mel+Pdn vs high-dose Mel	MM/newly diagnosed	III	PFS, ORR, OS
Len+Bort+Dex vs	MM/untreated	I/II	ORR
Len+Bort+Dex+CTX
Len+Dex+Thal	MM/Dex previously treated	III	PFS, ORR, OS
Len+Dex+Thal	MM/relapsed, refractory	II	Efficacy, safety
Len+Perifosine+Dex	MM	I	Safety, adverse events safety
Len+SGN-40+Dex	MM	I
Len+Dex vs Dex	MM/previously treated	III	TTP, OS
Len+Mel+Pdn	MM/untreated patients	I/II	Toxicity, TTP, OS, ORR
Len+Mel	MM/untreated patients	II	Toxicity, tumor response, TTP, OS, DFS
Len+Rituximab	WM	II	ORR, TTP, safety

Abbreviations: Len, lenalidomide; Dex, dexamethasone; Mel, melphalan; Pdn, prednisone; Bort, Bortezomib; CTX, cyclophosphamide; Thal, thalidomide; ORR, overall response rate; PFS, progression-free survival; OS, overall survival; TTP: time to progression; DFS, disease-free survival.

Table 3 Ongoing clinical trials using Bortezomib-based regimens in MM and WM (www.clinicaltrials.gov)

Treatment regimen	Disease	Phase	Endpoints
Bort + Perifosine +/− Dex	MM/relapsed, refractory, previously treated with Bortezomib	I/II	Toxicity, ORR
Bort + CCI-779	MM/relapsed, relapsed/refractory	I/II	Safety, MTD, TTP, PFS, OS
Bort+Doxil+Dex followed by Thal+Dex +/− Bort	MM	II	Toxicity, disease response
Bort+Sorafenib	MM/relapsed, refractory	I/II	ORR, PFS
Bort+Doxil+Mel	MM/relapsed, refractory	I/II	Safety, tolerability, MTD
Bort+Doxil	MM	II	ORR, toxicity, OS, PFS, TTP
Bort+AsO3 +Vitamin C	MM	I/II	Safety, toxicity,
Bort+Samarium153	MM/relapsed, refractory	I	Toxicity, MTD, TTP, PFS, OS
Bort+Vorinostat (SAHA)	MM/relapsed, refractory	I	MTD, toxicity
Bort+Ascorbic Acid+Mel	MM/newly diagnosed	II	Safety, tolerability, ORR, TTP, TTR, PFS, OS
Bort+Dex+Doxil followed by CTX	MM/post first line therapy; relapsed/refractory Bortezomib naïve	II	Efficacy, safety
Bort+Thal+Dex	MM/relapsed, refractory	II	ORR, OS, PFS, toxicity
Bort+Dex+Thal vs Bort+Dex+Thal+CTX	MM/newly diagnosed candidate for high-dose therapy and stem cell transplantation	II	ORR, TTP, PFS
Bort	WM	II	ORR, safety, tolerability
Bort+Rituximab	WM/relapsed, refractory	II	ORR, safety, TTP
Bort+Rituximab	WM/newly diagnosed	II	ORR, ability to collect stem cells, ORR, TTP, toxicity
Bort+Thal+Dex vs Bort+Dex vs Bort+Mel+Pdn	MM/untreated	III	PFS
Bort+Thal+Dex +/−Adriamycin	MM/relapsed, refractory	III	Efficacy, toxicity
Bort+Dex+Rituximab	WM	II	Safety, tolerability, ORR, TTP
Bort	WM/untreated or relapsed	II	Toxicity, ORR, TTP, stable disease duration, response duration

Abbreviations: Bort, Bortezomib; Dex, dexamethasone; Doxil, liposomal doxorubicine; Thal, thalidomide; CTX, cyclophosphamide; Mel, melphalan; AsO₃, arsenic trioxide; ORR, overall response rate; MTD, maximum tolerated dose; TTP, time to progression; PFS, progression-free survival; OS, overall response.