CVAEs reported in landmark clinical trials evaluating cellular therapies
| Study . | Trial name|| . | Study phase . | Drug class . | Drug name . | Indication . | Intervention arm sample size . | Median follow-up duration, mo∗ . | Rate of CRS† . | Rate of treatment-emergent CVAEs . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arrhythmia‡ . | Hypertension . | Coagulopathy§ . | Others . | |||||||||
| Maude et al1,43 | ELIANA | Phase 1/2 | CAR-T | Tisagenlecleucel | R/R preB-ALL | 79 | 13.1 | 61 (77%) | 2 (4%) | 145 (19%) | 5 (6%) | Cardiac failure, 10 (9%) |
| Schuster et al32,43 | JULIET | Phase 2 | CAR-T | Tisagenlecleucel | R/R DLBCL | 115 | 28.6 | 85 (74%) | 12 (10%) | 5 (4%) | 5 (4%) | Cardiac failure, 1 (1%) |
| Fowler et al35,43 | ELARA | Phase 2 | CAR-T | Tisagenlecleucel | R/R FL | 97 | 16.6 | 51 (53%) | 4 (4%) | 5 (5%) | 2 (2%) | NA |
| Neelapu et al31,44 | ZUMA-1 | Phase 1/2 | CAR-T | Axicabtagene ciloleucel | R/R LBCL | 108 | 8.7 | 101 (94%) | 25 (23%) | 16 (15%) | 2 (2%) | Cardiac failure, 6 (6%) Cardiac arrest, 4 (4%) |
| Jacobson et al36,44 | ZUMA-5 | Phase 2 | CAR-T | Axicabtagene ciloleucel | R/R iNHL | 146 | 17.5 | 123 (84%) | 31 (21%) | 19 (13%) | 9 (6%) | Cardiac failure, 3 (2%) |
| Locke et al44,45 | ZUMA-7 | Phase 3 | CAR-T | Axicabtagene ciloleucel | R/R LBCL | 168 | 24.9 | 155 (92%) | 24 (14%) | 15 (9%) | 15 (9%) | Cardiac failure, 2 (1%) |
| Wang et al33,46 | ZUMA-2 | Phase 2 | CAR-T | Brexucabtagene autoleucel | R/R MCL | 82 | 12.3 | 75 (91%) | 8 (10%)¶ | 15 (18%) | 8 (10%) | NA |
| Shah et al30,46 | ZUMA-3 | Phase 1/2 | CAR-T | Brexucabtagene autoleucel | R/R preB-ALL | 78 | 16.4 | 72 (92%) | 12 (15%) | 10 (13%) | 13 (17%) | Cardiac failure, 3 (4%) |
| Kamdar et al3,47 | TRANSFORM | Phase 2 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 89 | 6.2 | 44 (49%) | 13 (15%)# | 6 (7%) | NA | NA |
| Sehgal et al38,47 | PILOT | Phase 2 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 61 | 12.3 | 24 (39%) | 6 (10%)# | 6 (10%) | NA | NA |
| Abramson et al34,47 | TRANSCEND | Phase 1 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 268 | 18.8 | 123 (46%) | 16 (6%) | 38 (14%) | NA | Cardiomyopathy 4 (1.5%) |
| Siddiqi et al48 | TRANSCEND CLL | Phase 1/2 | CAR-T | Lisocabtagene maraleucel | R/RCLL | 117 | 21.1 | 99 (85%) | NA | NA | NA | NA |
| Munshi et al4,49 | KarMMa | Phase 2 | CAR-T | Idecabtagene vicleucel | R/R MM | 127 | 13.3 | 108 (85%) | 6 (4.7%) | 14 (11%) | 11 (9%) | Cardiomyopathy 2 (1.6%) |
| Rodriguez-Otero et al49,50 | KarMMa-3 | Phase 3 | CAR-T | Idecabtagene vicleucel | R/R MM | 222 | 18.8 | 202 (91%) | 16 (7%) | 31 (14%) | 31 (14%) | NA |
| Berdeja et al39,51 | CARTITUDE-1 | Phase 1/2 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 97 | 12.4 | 92 (95%) | 8 (8%) | 18 (19%) | 21 (22%) | NA |
| Cohen et al40 | CARTITUDE-2 | Phase 2 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 20 | 11.3 | 12 (60%) | NA | NA | NA | NA |
| San-Miguel et al5,51 | CARTITUDE-4 | Phase 3 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 188 | 15.9 | 147 (78%) | 6 (3%) | 13 (7%) | 9 (5%) | NA |
| Kantarjian et al6,52 | TOWER | Phase 3 | BTE | Blinatumomab | R/R preB-ALL | 267 | 11.7 | 38 (14.2%) | NA | 17 (6.4%) | NA | AMI, 1 (0.4%) Cardiac arrest, 1 (0.4%) Cardiac failure, 1 (0.4%) Pericardial effusion, 1 (0.4%) |
| Locatelli et al52,53 | RIALTO | Phase 3 | BTE | Blinatumomab | R/R preB-ALL | 110 | 17.4 | 18 (16.4%)∗∗ | NA | NA | NA | NA |
| Martinelli et al54 | ALCANTARA | Phase 2 | BTE | Blinatumomab | R/R preB-ALL | 45 | 16.1 | 4 (9%) | NA | NA | NA | NA |
| Gökbuget et al55 | BLAST | Phase 2 | BTE | Blinatumomab | MRD positive preB-ALL | 116 | 30 | 4 (3%) | NA | NA | NA | NA |
| Moreau et al7,56 | MajesTEC-1 | Phase 2 | BTE | Teclistamab | R/R MM | 165 | 14.1 | 119 (72%) | 26 (16%) | 20 (12%) | NA | NA |
| Dickinson et al8,57 | NP30179 | Phase 2 | BTE | Glofitamab | R/R DLBCL | 154 | 12.6 | 102 (66%) | NA | NA | NA | NA |
| Budde et al9,58 | GO29781 | Phase 1 | BTE | Mosunetuzumab | R/R FL | 90 | 12.6 | 40 (44%) | NA | NA | NA | NA |
| Thieblemont et al10,59 | EPCORE NHL-1 | Phase 1/2 | BTE | Epcoritamab | R/R LBCL | 157 | 10.7 | 80 (51%) | 16 (10%) | NA | NA | AMI, 1 (0.6%) |
| Chesney et al60,61 | C-144–01 | Phase 2 | TIL | Lifileucel | Unresectable/metastatic melanoma | 156 | 27.6 | 5 (3.2%) | 74 (47.4%)# | 21 (13.5%) | NA | Hypotension, 52 (33.3%) |
| Study . | Trial name|| . | Study phase . | Drug class . | Drug name . | Indication . | Intervention arm sample size . | Median follow-up duration, mo∗ . | Rate of CRS† . | Rate of treatment-emergent CVAEs . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arrhythmia‡ . | Hypertension . | Coagulopathy§ . | Others . | |||||||||
| Maude et al1,43 | ELIANA | Phase 1/2 | CAR-T | Tisagenlecleucel | R/R preB-ALL | 79 | 13.1 | 61 (77%) | 2 (4%) | 145 (19%) | 5 (6%) | Cardiac failure, 10 (9%) |
| Schuster et al32,43 | JULIET | Phase 2 | CAR-T | Tisagenlecleucel | R/R DLBCL | 115 | 28.6 | 85 (74%) | 12 (10%) | 5 (4%) | 5 (4%) | Cardiac failure, 1 (1%) |
| Fowler et al35,43 | ELARA | Phase 2 | CAR-T | Tisagenlecleucel | R/R FL | 97 | 16.6 | 51 (53%) | 4 (4%) | 5 (5%) | 2 (2%) | NA |
| Neelapu et al31,44 | ZUMA-1 | Phase 1/2 | CAR-T | Axicabtagene ciloleucel | R/R LBCL | 108 | 8.7 | 101 (94%) | 25 (23%) | 16 (15%) | 2 (2%) | Cardiac failure, 6 (6%) Cardiac arrest, 4 (4%) |
| Jacobson et al36,44 | ZUMA-5 | Phase 2 | CAR-T | Axicabtagene ciloleucel | R/R iNHL | 146 | 17.5 | 123 (84%) | 31 (21%) | 19 (13%) | 9 (6%) | Cardiac failure, 3 (2%) |
| Locke et al44,45 | ZUMA-7 | Phase 3 | CAR-T | Axicabtagene ciloleucel | R/R LBCL | 168 | 24.9 | 155 (92%) | 24 (14%) | 15 (9%) | 15 (9%) | Cardiac failure, 2 (1%) |
| Wang et al33,46 | ZUMA-2 | Phase 2 | CAR-T | Brexucabtagene autoleucel | R/R MCL | 82 | 12.3 | 75 (91%) | 8 (10%)¶ | 15 (18%) | 8 (10%) | NA |
| Shah et al30,46 | ZUMA-3 | Phase 1/2 | CAR-T | Brexucabtagene autoleucel | R/R preB-ALL | 78 | 16.4 | 72 (92%) | 12 (15%) | 10 (13%) | 13 (17%) | Cardiac failure, 3 (4%) |
| Kamdar et al3,47 | TRANSFORM | Phase 2 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 89 | 6.2 | 44 (49%) | 13 (15%)# | 6 (7%) | NA | NA |
| Sehgal et al38,47 | PILOT | Phase 2 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 61 | 12.3 | 24 (39%) | 6 (10%)# | 6 (10%) | NA | NA |
| Abramson et al34,47 | TRANSCEND | Phase 1 | CAR-T | Lisocabtagene maraleucel | R/R LBCL | 268 | 18.8 | 123 (46%) | 16 (6%) | 38 (14%) | NA | Cardiomyopathy 4 (1.5%) |
| Siddiqi et al48 | TRANSCEND CLL | Phase 1/2 | CAR-T | Lisocabtagene maraleucel | R/RCLL | 117 | 21.1 | 99 (85%) | NA | NA | NA | NA |
| Munshi et al4,49 | KarMMa | Phase 2 | CAR-T | Idecabtagene vicleucel | R/R MM | 127 | 13.3 | 108 (85%) | 6 (4.7%) | 14 (11%) | 11 (9%) | Cardiomyopathy 2 (1.6%) |
| Rodriguez-Otero et al49,50 | KarMMa-3 | Phase 3 | CAR-T | Idecabtagene vicleucel | R/R MM | 222 | 18.8 | 202 (91%) | 16 (7%) | 31 (14%) | 31 (14%) | NA |
| Berdeja et al39,51 | CARTITUDE-1 | Phase 1/2 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 97 | 12.4 | 92 (95%) | 8 (8%) | 18 (19%) | 21 (22%) | NA |
| Cohen et al40 | CARTITUDE-2 | Phase 2 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 20 | 11.3 | 12 (60%) | NA | NA | NA | NA |
| San-Miguel et al5,51 | CARTITUDE-4 | Phase 3 | CAR-T | Ciltacabtagene autoleucel | R/R MM | 188 | 15.9 | 147 (78%) | 6 (3%) | 13 (7%) | 9 (5%) | NA |
| Kantarjian et al6,52 | TOWER | Phase 3 | BTE | Blinatumomab | R/R preB-ALL | 267 | 11.7 | 38 (14.2%) | NA | 17 (6.4%) | NA | AMI, 1 (0.4%) Cardiac arrest, 1 (0.4%) Cardiac failure, 1 (0.4%) Pericardial effusion, 1 (0.4%) |
| Locatelli et al52,53 | RIALTO | Phase 3 | BTE | Blinatumomab | R/R preB-ALL | 110 | 17.4 | 18 (16.4%)∗∗ | NA | NA | NA | NA |
| Martinelli et al54 | ALCANTARA | Phase 2 | BTE | Blinatumomab | R/R preB-ALL | 45 | 16.1 | 4 (9%) | NA | NA | NA | NA |
| Gökbuget et al55 | BLAST | Phase 2 | BTE | Blinatumomab | MRD positive preB-ALL | 116 | 30 | 4 (3%) | NA | NA | NA | NA |
| Moreau et al7,56 | MajesTEC-1 | Phase 2 | BTE | Teclistamab | R/R MM | 165 | 14.1 | 119 (72%) | 26 (16%) | 20 (12%) | NA | NA |
| Dickinson et al8,57 | NP30179 | Phase 2 | BTE | Glofitamab | R/R DLBCL | 154 | 12.6 | 102 (66%) | NA | NA | NA | NA |
| Budde et al9,58 | GO29781 | Phase 1 | BTE | Mosunetuzumab | R/R FL | 90 | 12.6 | 40 (44%) | NA | NA | NA | NA |
| Thieblemont et al10,59 | EPCORE NHL-1 | Phase 1/2 | BTE | Epcoritamab | R/R LBCL | 157 | 10.7 | 80 (51%) | 16 (10%) | NA | NA | AMI, 1 (0.6%) |
| Chesney et al60,61 | C-144–01 | Phase 2 | TIL | Lifileucel | Unresectable/metastatic melanoma | 156 | 27.6 | 5 (3.2%) | 74 (47.4%)# | 21 (13.5%) | NA | Hypotension, 52 (33.3%) |
Reported AEs are treatment emergent, unless otherwise specified. Absolute numbers are derived from percentages and may not represent actual counts.
AMI, acute myocardial infarction; aPTT, activated partial thromboplastin time; iNHL, indolent non-Hodgkin lymphoma; INR, international normalized ratio; MRD, minimal residual disease; NA, not available; PT, prothrombin time; R/R CLL, relapse/refractory chronic lymphocytic lymphoma; R/R DLBCL, relapse/refractory diffuse large B-cell lymphoma; R/R FL, relapse/refractory follicular lymphoma; R/R LBCL, relapse/refractory large B-cell lymphoma; R/R MCL, relapse/refractory mantle cell lymphoma; R/R MM, relapse/refractory multiple myeloma; R/R preB-ALL, relapse/refractory precursor B-cell acute lymphoblastic leukemia.
When applicable, median follow-up for overall survival is reported.
Any-grade CRS.
When applicable, any of the following are reported as mention: atrial fibrillation, atrial flutter, atrial tachycardia, bradycardia, cardiac arrest, electrocardiogram QT prolonged, electrocardiogram T wave inversion, pulseless electrical activity, sinus bradycardia, supraventricular tachycardia, and ventricular tachycardia. Note, due to the lack of consistency of reporting among trials, the rate reported may coincide with any combination of the aforementioned arrhythmias.
Coagulopathy refers to reporting of any of the following events: disseminated intravascular coagulation, elevated PT/aPTT, elevated INR, and elevated D-dimer.
When applicable, the reported AEs are from the FDA drug insert because it provides more comprehensive data on the reported CVAEs.
Reported rate for both bradyarrhythmia and nonventricular arrhythmia.
Reported as tachycardia includes atrial fibrillation, atrial flutter, supraventricular tachycardia, sinus tachycardia, and tachycardia.
Reported as treatment-related AEs.