Addition of CAR T-Cell Therapy to Stem Cell Transplantation in Refractory Multiple Myeloma
Posted: Thursday, May 31, 2018
Administering autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19, known as CTL019, may improve the duration of response compared with standard therapies in patients with relapsed or refractory multiple myeloma, discovered researchers at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia. Led by Alfred L. Garfall, MD, they sought to determine whether minor, less-differentiated components of the multiple myeloma clone participate in disease pathogenesis. Their findings were published in JCI Insight.
“Our results provide a framework for understanding heterogeneity between patients in the immunophenotype of myeloma-propagating cells,” stated the investigators.
Participants were given CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT). All had previously undergone ASCT with less than 1-year progression-free survival, and most had disease that exhibited genetic or clinical features associated with a poor prognosis.
Of the 10 patients receiving therapy, 2 had significantly longer progression-free survival after ASCT plus CTL019 compared with prior ASCT (479 vs. 181 days, 249 vs. 127 days). The addition of CTL019 appeared to be safe, with most toxicity attributable to ASCT. Favorable clinical outcomes correlated with the emergence of humoral and cellular immune responses against the stem-cell antigen Sox2 and peak CTL019 frequency in bone marrow.
“Beyond multiple myeloma, our results provide clinical evidence in support of the cancer stem cell hypothesis and the ability of potent immunotherapies targeted to minor disease-propagating populations to favorably alter the clinical trajectory of advanced cancers,” concluded Dr. Garfall and colleagues.