TY - JOUR
T1 - Indatuximab Ravtansine (BT062) Monotherapy in Patients With Relapsed and/or Refractory Multiple Myeloma
AU - Jagannath, Sundar
AU - Heffner, Leonard T.
AU - Ailawadhi, Sikander
AU - Munshi, Nikhil C.
AU - Zimmerman, Todd M.
AU - Rosenblatt, Jacalyn
AU - Lonial, Sagar
AU - Chanan-Khan, Asher
AU - Ruehle, Markus
AU - Rharbaoui, Faiza
AU - Haeder, Thomas
AU - Wartenberg-Demand, Andrea
AU - Anderson, Kenneth C.
PY - 2019/6
Y1 - 2019/6
N2 - Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138, which is overexpressed on multiple myeloma (MM) cells. Patients and Methods: We report from 2 clinical studies of patients with relapsed and/or refractory MM previously treated with an immunomodulatory drug and a proteasome inhibitor. Single- and multi-dosing schedules were investigated to define dose-limiting toxicities, maximum tolerated dose (MTD), recommended phase II dose, and to describe safety, efficacy, and pharmacokinetics. Results: In the first-in-human study, indatuximab ravtansine was administered to 32 patients on day 1 of each 21-day cycle. The MTD was 160 mg/m2. In the phase I/IIa study, indatuximab ravtansine was administered to 35 patients on days 1, 8, and 15 of each 28-day cycle, and the MTD/recommended phase II dose was 140 mg/m2. Most (88%) adverse events were grade 1 or 2, the most common being diarrhea and fatigue. There was rapid clearance of indatuximab ravtansine and no relevant accumulation. Over 75% of heavily pretreated patients achieved stable disease or better. With the multi-dose schedule, minor and partial responses occurred in 14.7% of patients, the median time to progression was 3 months, and the median overall survival was 26.7 months. Conclusion: Our data support further investigation of indatuximab ravtansine as part of a combination regimen for relapsed and/or refractory MM.
AB - Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138, which is overexpressed on multiple myeloma (MM) cells. Patients and Methods: We report from 2 clinical studies of patients with relapsed and/or refractory MM previously treated with an immunomodulatory drug and a proteasome inhibitor. Single- and multi-dosing schedules were investigated to define dose-limiting toxicities, maximum tolerated dose (MTD), recommended phase II dose, and to describe safety, efficacy, and pharmacokinetics. Results: In the first-in-human study, indatuximab ravtansine was administered to 32 patients on day 1 of each 21-day cycle. The MTD was 160 mg/m2. In the phase I/IIa study, indatuximab ravtansine was administered to 35 patients on days 1, 8, and 15 of each 28-day cycle, and the MTD/recommended phase II dose was 140 mg/m2. Most (88%) adverse events were grade 1 or 2, the most common being diarrhea and fatigue. There was rapid clearance of indatuximab ravtansine and no relevant accumulation. Over 75% of heavily pretreated patients achieved stable disease or better. With the multi-dose schedule, minor and partial responses occurred in 14.7% of patients, the median time to progression was 3 months, and the median overall survival was 26.7 months. Conclusion: Our data support further investigation of indatuximab ravtansine as part of a combination regimen for relapsed and/or refractory MM.
KW - Antibody-drug conjugate
KW - CD138
KW - Monoclonal antibody
KW - Multiple-dose
KW - Syndecan-1
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U2 - 10.1016/j.clml.2019.02.006
DO - 10.1016/j.clml.2019.02.006
M3 - Article
C2 - 30930134
AN - SCOPUS:85063451981
VL - 19
SP - 372
EP - 380
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2669
IS - 6
ER -