We are international
Donate
TEXT SIZE   


Safety and efficacy of anti-CD19 chimeric antigen receptor (CAR)-modified autologous T cells (CTL019) in advanced multiple myeloma

Dr. Edward A. Stadtmauer
Abramson Cancer Center
Philadelphia, Pennsylvania USA

06.09.15

Background: CTL019, a 2nd-generation anti-CD19 CAR transduced via lentiviral vector, can induce regression of refractory B cell malignancies. Though multiple myeloma (MM) is reported to be CD19-negative, we hypothesized that CTL019 would exhibit efficacy in MM due to low-level CD19 expression on MM plasma cells (PC) or CD19 expression in drug-resistant, disease-propagating subsets of the MM clone. Here, we report initial results of an ongoing phase 1 study of CTL019 in patients with advanced MM.

Methods: MM patients are eligible if they experienced disease progression within one year of a prior autologous stem cell transplantation (ASCT) and are medically fit to undergo second ASCT. Study therapy consists of 1-5x107CTL019 cells infused 12-14 days after high-dose melphalan + ASCT.

Results: 4 subjects have been treated and have completed 30-220 days of follow-up. Median prior lines of therapy is 7.5 (range 3-10). 3/4 have unfavorable cytogenetics; 1/4 had PC leukemia. Adverse events have included hypogammaglobulinemia (4/4) and grade 1 cytokine release syndrome (1/4). 3 subjects are evaluable for response. In all 3 subjects, CTL019 engraftment was achieved (peak 0.1-0.6% of peripheral blood T cells at days 30-42), and B cells were not detectable by flow cytometry in blood or marrow at day 42. At day 100, subject #1 attained MRD-negative stringent complete response (CR), and Subject #2 attained MRD-negative unconfirmed (due to unevaluable bone marrow core) CR. Response duration in Subject #1 has surpassed the response duration after this subject’s prior ASCT (i.e., remission inversion). 99.95% of Subject #1’s MM PC were CD19-negative by flow cytometry and RTPCR, indicating that efficacy in this subject is not due to direct cytotoxicity of CTL019 against the dominant MM PC population. Subject #3 experienced disease progression at day 43. Updated results on the first 5 subjects will be presented.

Conclusions: Preliminary data suggest that CTL019 can be manufactured from and safely administered to refractory MM patients. CTL019 can engraft and induce B cell aplasia after salvage ASCT. Ongoing, deep responses in 2 of 3 evaluable subjects are encouraging with respect to potential efficacy. Clinical trial information: NCT02135406


 related articles
Dr. Kenneth Anderson - ASCO 2015 Highlights
Dr. Paul Richardson - ASCO 2015 Highlights
Dr. Shaji Kumar overview of ASCO 2015
Dr. Morie A. Gertz ASCO 2015 Overview
Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed multiple myeloma (RMM): Results from the phase III study ENDEAVOR
Safety and efficacy of anti-CD19 chimeric antigen receptor (CAR)-modified autologous T cells (CTL019) in advanced multiple myeloma
A randomized phase II study of bortezomib (Btz)/dexamethasone (dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Cardiac and renal biomarker responses in a phase 1/2 study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction.
Phase II MMRC trial of extended treatment with carfilzomib (CFZ), lenalidomide (LEN), and dexamethasone (DEX) plus autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM)
ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Phase I interim safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory (R/R) multiple myeloma (MM)
Phase II study of daratumumab (DARA) monotherapy in patients with > 3 lines of prior therapy or double refractory multiple myeloma (MM)


You might also be interested in:

Overview
Dr. Kenneth Anderson - ASCO 2015 Highlights

Dr. Ken Anderson
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


Dr. Paul Richardson - ASCO 2015 Highlights

Dr. Paul Richardson
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


Dr. Shaji Kumar overview of ASCO 2015

Dr. Shaji Kumar's overview on what abstracts and posters generated the most excitement for the field of Multiple Myeloma at ASCO 2015.


Dr. Morie A. Gertz ASCO 2015 Overview

Dr. Morie A. Gertz overview on Frontline Therapies presented at ASCO 2015.


Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed multiple myeloma (RMM): Results from the phase III study ENDEAVOR

Dr. Meletios Dimopoulos
National and Kapodistrian
University of Athens
Athens, Greece


Safety and efficacy of anti-CD19 chimeric antigen receptor (CAR)-modified autologous T cells (CTL019) in advanced multiple myeloma

Dr. Edward A. Stadtmauer
Abramson Cancer Center
Philadelphia, Pennsylvania USA


A randomized phase II study of bortezomib (Btz)/dexamethasone (dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).

Dr. Adrzej Jakubowiak
University of Chicago Medical Center
Chicago, Illinois, USA


Cardiac and renal biomarker responses in a phase 1/2 study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction.

Dr. Morie Gertz
Mayo Clinic
Rochester, MN


Phase II MMRC trial of extended treatment with carfilzomib (CFZ), lenalidomide (LEN), and dexamethasone (DEX) plus autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM)

Dr. Andrzej Jakubowiak
University of Chicago Medical Center
Chicago, Illinois,  USA


ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).

Dr. Sagar Lonial
Emory University
Atlanta, GA, USA


Phase I interim safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory (R/R) multiple myeloma (MM)

Dr. Shaji Kumar
Mayo Clinic
Rochester, MN, USA


Phase II study of daratumumab (DARA) monotherapy in patients with > 3 lines of prior therapy or double refractory multiple myeloma (MM)

Dr. Sagar Lonial
Emory University
Atlanta, GA, USA