Anti CD38 monoclonal antibodies for multiple myeloma treatment

Figures & data

Figure 1. Mechanism of action of anti-CD38.

CD38;

anti-CD38 (Daratumumab or Isatuximab); CDC, Complement Dependent Cytotoxicity; ADCC, Antibody Dependent Cell-mediated Cytotoxicity; ADCP, Antibody-Dependent Cellular Phagocytosis.

Table 1. Selected trials of daratumumab in multiple myeloma

Clinical Trial	Phase	Setting	Treatment	ORR (%)	CR (%)	MRD neg (%)
NCT 00574288 (GEN501)	1/2	RRMM	Monotherapy, dose-escalation	36	4,7	NA
NCT 02316106 (SMM2001 - CENTAURUS)	2	SMM (intermediate-R, high-R)	Monotherapy	56,1 (intense arm) 53,7 (intermediate arm) 37,5 (short arm)	5,0 10,0 0,0	NA
NCT 01985126 (MMY2002 – SIRIUS)	2	RRMM	Monotherapy	29,2	2,8	NA
GEN501 + SIRIUS	1/2	RRMM	Monotherapy	31,1	4,7	NA
NCT 01615029 (GEN503)	1/2	RRMM	Dara-Rd, dose escalation	81	25,0	34,4
NCT 03158688 (CANDOR)	3	RRMM	Dara-Kd vs Kd	84,3 vs 74,7	29,0 vs 10,0	14 vs 3
NCT 02874742 (MMY2004 – GRIFFIN)	2	NDMM eligible for HDT or ASCT	Dara-RVd vs RVd	99 vs 91,8	80 vs 61	51 vs 20
NCT 03357952 (MMY2036)	multiphase	RRMM	Anti PD1-Dara	44,4	NA	NA
NCT 02076009 (MMY3003 – POLLUX)	3	RRMM	Dara-Rd vs Rd	92,9 vs 76,4	43,1 vs 19,2	22,4 vs 4,6
NCT 02136134 (MMY 3004 – CASTOR)	3	RRMM	Dara-Vd vs Vd	85 vs 63 92 vs 74 (1 prior line treatment)	30 vs 10 43 vs 15	14 vs 2 20 vs 3
NCT 02541383 (MMY3006 – CASSIOPEIA)	3	NDMM eligible for ASCT	Dara-VTd vs VTd	92,6 vs 89,9	39 vs 26	64 vs 44
NCT02195479 (MMY3007 - ALCYONE)	3	NDMM ineligible for HDT and ASCT	Dara-VMP vs VMP	90,9 vs 73,9	42,6 vs 24,4	22,3 vs 6,2
NCT 02252172 (MMY3008 – MAIA)	3	NDMM ineligible for HDT and ASCT	Dara-Rd vs Rd	92,9 vs 81.3	47,6 vs 24,9	24,2 vs 7,3
NCT 03412565 (MMY2040 – PLEIADES)	2	NDMM	Dara sc VMP vs Dara sc VRd vs Dara sc Rd	89,6 97,0 93,8	47,8 16,5 38,5	16,4 n.a 15,4
NCT 03180736 (MMY3013 – APOLLO)	3	RRMM	Dara sc Pd vs Pd	68,9 vs 46,4	25 vs 4	9 vs 2

Table 2. Selected trials of isatuximab in multiple myeloma

Clinical Trial	Phase	Setting	Treatment	ORR (%)	CR (%)	MRD neg (%)
*First -in human isatuxiamb	1	RRMM	Monotherapy, dose-escalation	18,2 (1–5 mg/kg) 23,8 (≥10 mg/kg)	0 1,6	NA
NCT 02283775  (PomdeSAR)	1 B	RRMM	Isa-Pd	62,2	4,4	NA
NCT 02332850	1 B	RRMM	Isa-Kd	66	3,4	NA
NCT 01749969	1 B	RRMM	Isa-Rd	56	3,8	NA
NCT 02990338  (ICARIA—MM)	3	RRMM	Isa-Pd vs Pd	60 vs 35	5 vs 2	5 vs 0
NCT 03275285  (IKEMA)	3	RRMM	Isa-Kd vs Kd	87 vs 83	40 vs 28	30 vs 13