Selected phase 2 and phase 3 studies evaluating novel agents in relapsed or refractory MZL
| Study . | N pts . | MZL subtype . | N prior lines . | Agent/regimen . | ORR, % (CR) . | mPFS,mo . | mDOR,mo . | Grade 3-4 AEs . |
|---|---|---|---|---|---|---|---|---|
| BTK inhibitors | ||||||||
| Noy et al65,66 | 63 | EMZL n = 32 NMZL n = 17 SMZL n = 14 | 2 (1-9) | Ibrutinib 560 mg/d | 58 (10) | 15.8 | 27.6 | Infections (22%), anemia (16%), atrial fibrillation (8%) |
| MAGNOLIA67 | 68 | EMZL n = 26 NMZL n = 26 SMZL n = 12 Uncertain n = 4 | 2 (1-6) | Zanubrutinib 160 mg twice daily | 68 (26) | NR (82.5 at 15 mo) | NR (93% at 12 mo) | Neutropenia (10.3%), infections (16.2%) |
| Strati et al68 | 43 | EMZL n = 19 NMZL n = 13 SMZL n = 11 | 2 (1-4) | Acalabrutinib 100 mg twice daily | 53 (13) | 27 | 75.8% (12 mo) | Neutropenia (14%), infections (7%) |
| PI3K inhibitors | ||||||||
| 101-0980 | 15 | NA | 2 (2-9) | Idelalisib 150 mg twice daily | 46.7 (6.7) | 6.6 | 18.4 | Neutropenia (27%), AST/ALT elevation (13%), diarrhea (13%), pneumonia (7%) |
| DYNAMO81 | 18 | EMZL n = 9 NMZL n = 4 SMZL n = 5 | 2 (1-8) | Duvelisib 25 mg twice daily | 39 (5.5) | 15.5 | NA | Neutropenia (28%), diarrhea (17%) |
| CHRONOS-182 | 23 | EMZL n = 4 NMZL n = 15 SMZL n = 4 | 3 (2-9) | Copanlisib 60 mg ev, days 1, 8, 15 q28 | 70 (9) | 24.1 | 17.4 | Hyperglycemia (39%), hypertension (39%), neutropenia (13%), diarrhea (13%), pneumonia (13%) |
| CHRONOS-370 (phase 3) | 95 | EMZL n = 35 NMZL n = 37 SMZL n = 23 | 2 | Copanlisib-rituximab | 86 (39) | 22.1 | 20.4 | Hyperglycemia (56%), hypertension (40%), neutropenia (16%), pneumonia (7%), diarrhea (5%) |
| UNITY-NHL71 | 69 | EMZL n = 38 NMZL n = 20 SMZL n = 11 | 2 (1-6) | Umbralisib 800 mg/d | 49.2 (15.9) | NR (50.5% at 24 mo) | NR | Diarrhea (2.9%), ALT/AST elevation (4.3%) |
| UNITY-NHL83 | 72 | EMZL n = 33 NMZL n = 31 SMZL n = 8 | 2 (1-9) | Umbralisib-ublituximab | 70 (21) | 16.6 | NR | Neutropenia (18%), diarrhea (13%), ALT/AST elevation (15%) |
| CITADEL-20472 | 100 | EMZL n = 34 NMZL n = 31 SMZL n = 35 | 2 (1-8) | Parsaclisib 20 mg/d (8 weeks), then 20 mg once weekly or 2.5 mg/d | 58 (6) | 16.5 | 12.2 | Diarrhea (12%), neutropenia (10%), pneumonia (9%) |
| Lenalidomide | ||||||||
| AUGMENT73 (phase 3) | 63 | EMZL n = 30 NMZL n = 18 SMZL n = 15 | 1 (1-12) | Lenalidomide 20 mg (days 1-21), 12 cycles + R | 65 (29) | 20.2 | 17.4 | Neutropenia (50%) |
| MAGNIFY (phase 3b) | 74 | EMZL n = 15 NMZL n = 43 SMZL n = 16 | 2 | Lenalidomide 20 mg (days 1-21), 12 cycles + R(+18 mo maint. R2 vs R) | 68 (39) | 41.2 | 38.6 | Neutropenia (37%) |
| CAR T | ||||||||
| ZUMA-575 | 24 | EMZL n = 17 NMZL n = 7 SMZL n = 0 | 3 (2-5) | Axicabtagene ciloleucel 2 × 106/kg | 83 (63) | 17.3 | NR | CRS (8%), ICANS (36%), infections (18%) |
| Study . | N pts . | MZL subtype . | N prior lines . | Agent/regimen . | ORR, % (CR) . | mPFS,mo . | mDOR,mo . | Grade 3-4 AEs . |
|---|---|---|---|---|---|---|---|---|
| BTK inhibitors | ||||||||
| Noy et al65,66 | 63 | EMZL n = 32 NMZL n = 17 SMZL n = 14 | 2 (1-9) | Ibrutinib 560 mg/d | 58 (10) | 15.8 | 27.6 | Infections (22%), anemia (16%), atrial fibrillation (8%) |
| MAGNOLIA67 | 68 | EMZL n = 26 NMZL n = 26 SMZL n = 12 Uncertain n = 4 | 2 (1-6) | Zanubrutinib 160 mg twice daily | 68 (26) | NR (82.5 at 15 mo) | NR (93% at 12 mo) | Neutropenia (10.3%), infections (16.2%) |
| Strati et al68 | 43 | EMZL n = 19 NMZL n = 13 SMZL n = 11 | 2 (1-4) | Acalabrutinib 100 mg twice daily | 53 (13) | 27 | 75.8% (12 mo) | Neutropenia (14%), infections (7%) |
| PI3K inhibitors | ||||||||
| 101-0980 | 15 | NA | 2 (2-9) | Idelalisib 150 mg twice daily | 46.7 (6.7) | 6.6 | 18.4 | Neutropenia (27%), AST/ALT elevation (13%), diarrhea (13%), pneumonia (7%) |
| DYNAMO81 | 18 | EMZL n = 9 NMZL n = 4 SMZL n = 5 | 2 (1-8) | Duvelisib 25 mg twice daily | 39 (5.5) | 15.5 | NA | Neutropenia (28%), diarrhea (17%) |
| CHRONOS-182 | 23 | EMZL n = 4 NMZL n = 15 SMZL n = 4 | 3 (2-9) | Copanlisib 60 mg ev, days 1, 8, 15 q28 | 70 (9) | 24.1 | 17.4 | Hyperglycemia (39%), hypertension (39%), neutropenia (13%), diarrhea (13%), pneumonia (13%) |
| CHRONOS-370 (phase 3) | 95 | EMZL n = 35 NMZL n = 37 SMZL n = 23 | 2 | Copanlisib-rituximab | 86 (39) | 22.1 | 20.4 | Hyperglycemia (56%), hypertension (40%), neutropenia (16%), pneumonia (7%), diarrhea (5%) |
| UNITY-NHL71 | 69 | EMZL n = 38 NMZL n = 20 SMZL n = 11 | 2 (1-6) | Umbralisib 800 mg/d | 49.2 (15.9) | NR (50.5% at 24 mo) | NR | Diarrhea (2.9%), ALT/AST elevation (4.3%) |
| UNITY-NHL83 | 72 | EMZL n = 33 NMZL n = 31 SMZL n = 8 | 2 (1-9) | Umbralisib-ublituximab | 70 (21) | 16.6 | NR | Neutropenia (18%), diarrhea (13%), ALT/AST elevation (15%) |
| CITADEL-20472 | 100 | EMZL n = 34 NMZL n = 31 SMZL n = 35 | 2 (1-8) | Parsaclisib 20 mg/d (8 weeks), then 20 mg once weekly or 2.5 mg/d | 58 (6) | 16.5 | 12.2 | Diarrhea (12%), neutropenia (10%), pneumonia (9%) |
| Lenalidomide | ||||||||
| AUGMENT73 (phase 3) | 63 | EMZL n = 30 NMZL n = 18 SMZL n = 15 | 1 (1-12) | Lenalidomide 20 mg (days 1-21), 12 cycles + R | 65 (29) | 20.2 | 17.4 | Neutropenia (50%) |
| MAGNIFY (phase 3b) | 74 | EMZL n = 15 NMZL n = 43 SMZL n = 16 | 2 | Lenalidomide 20 mg (days 1-21), 12 cycles + R(+18 mo maint. R2 vs R) | 68 (39) | 41.2 | 38.6 | Neutropenia (37%) |
| CAR T | ||||||||
| ZUMA-575 | 24 | EMZL n = 17 NMZL n = 7 SMZL n = 0 | 3 (2-5) | Axicabtagene ciloleucel 2 × 106/kg | 83 (63) | 17.3 | NR | CRS (8%), ICANS (36%), infections (18%) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CR, complete response; CRS, cytokine release syndrome; ev, endovenous; FFP, freedom from progression; ICANS, immune effector cell–associated neurotoxicity syndrome; NA, not available; NR, not reached; R, rituximab; R2 , rituximab-lenalidomide; WW, watch and wait.