Table 1.
Immunotoxin and antibody drug conjugates for hematologic malignancies*
| Antigen |
Target Malignancy |
Agent | Cytotoxic |
Trials in Clinical Trials. Gov (1/2011) |
References (2006-2010) |
Toxicities* |
|---|---|---|---|---|---|---|
| CD3 | T-lineage ALL, NHL |
A-dmDT390- bisFv (UCHT1) |
Diphtheria toxin A |
+ | (35,59,60) | Fever, chills, nausea, hepatic, hypoalbuminemia, lymphopenia, viral reactivation |
| CD19 | B-lineage ALL, CLL, NHL, MM |
SAR3419 | Maytansinoid DM4 |
+ | (61) | Blurred vision |
| Anti-B4-BR | Ricin-blocked | (62) | Hepatic, myelosuppression, fever, anorexia, nausea, vomiting, myalgia, CLS |
|||
| CD19 & CD22 |
B-lineage ALL, CLL, NHL |
Combotox (mixture of HD37-dgA and RFB4-dgA) |
Ricin-dgA | + | (33) | Pancreatitis, anaphylaxis, graft-vs- host disease exacerbation, hypoalbuminemia, CLS |
| DT2219ARL (bispecific) |
diphtheria toxin | + | Unavailable | |||
| CD22 | B-lineage ALL, CLL, HCL, NHL |
Moxetumomab pasudotox, (HA22, CAT- 8015) |
Pseudomonas exotoxin A |
+ | (29,63-65) | Hypoalbuminemia, peripheral edema, fever, hepatic, CLS, HUS |
| BL22 (CAT- 3888) |
Pseudomonas exotoxin A |
(26,31,66) | Hypoalbuminemia, hepatic, HUS |
|||
| Inotuzumab ozogamicin (CMC-544) |
Calicheamicin | + | (40-42,67) | Thrombocytopenia, asthenia, nausea, neutropenia, hepatic, anorexia |
||
| CD25 | ALL, ATLL, CTCL, HL, NHL |
LMB-2 |
Pseudomonas exotoxin A |
+ | (19,68) | Hepatic, hypoalbuminemia, fever, cardiomyopathy |
| Denileukin difititox (Ontak) |
IL-2 conjugated to diphtheria exotoxin |
+ | (14,69) | Rigors, fever, nausea, CLS |
||
| CD30 | HL, NHL | Brentuximab vedotin (SGN- 35) |
Monomethyl auristatin E (MMAE) |
+ | (12,13) | Neutropenia, thrombocytopenia, lymphopenia, hyperglycemia, fatigue, fever, nausea, diarrhea, abdominal pain, peripheral neuropathy, electrolyte abnormalities |
| CD33 | AML, CML, MDS |
Gemtuzumab ozogamicin (Mylotarg) |
Calicheamicin | + | (70-72) | Myelosuppression, hepatic, veno- occlusive disease |
| AVE9633 | Maytansinoid DM4 |
(73) | Hepatic | |||
| HuM195/rgel | Gelonin | + | (74) | Allergy, fever | ||
| CD56 | MM, NK/T cell leukemias and NHL |
Lorvotuzumab mertansine (huN901-DM1, (IMGN901) |
Maytansinoid N(2′)-deacetyl- N(2′)-(3- mercapto- 1-oxopropyl)- maytansine (DM1) |
(57,75) | Fatigue, weakness, neuropathy |
|
| CD123 | AML, MDS, HCL |
DT388IL3 |
Diphtheria toxin A |
(56) | Hepatic, fever, chills, hypoalbuminemia, hypocalcemia, hypotension, CLS |
|
| CD138 | MM | BT062 | Maytansinoid (DM4) |
+ | (58,75-77) | Mucositis, hand/foot syndrome, dry eye, blurred vision |
Clinical trials noted in publications and abstracts from 2006-2010 and active clinical trials registered in ClinicalTrials.Gov as of 1/2011 are included. Toxicity summary includes common or severe adverse events associated with the specific agent based on previous reports.
ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; ATLL: adult T-cell leukemia/lymphoma; CLL: chronic lymphocytic leukemia; CLS: capillary leak syndrome; CTCL: cutaneous T-cell lymphoma; DCs: dendritic cells; dgA: deglycosylated ricin A chain; HL: Hodgkin lymphoma; HUS: hemolytic uremic syndrome; MCL: mantle cell lymphoma; MDS: myelodysplastic syndromes; MM: multiple myeloma; NHL: non-Hodgkin lymphoma; RNase: human ribonuclease; TRAIL: Tumor necrosis factor-related apoptosis-inducing ligand