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CD19-Targeted CAR T-Cell Therapy Shows Promise in Multiple Myeloma

Silas Inman @silasinman
Published: Friday, Jun 05, 2015

Dr Alfred L. Garfall

Alfred L. Garfall, MD

The CD19-targeted chimeric antigen receptor (CAR) T-cell therapy CTL019 demonstrated early evidence of activity and safety in patients with refractory multiple myeloma, according to data presented at the 2015 ASCO Annual Meeting. 

"These early results suggest that CTL019 and autologous transplant in patients with myeloma is safe and feasible," lead author Alfred L. Garfall, MD, from the Abramson Cancer Center at the University of Pennsylvania, said during his presentation. "We saw evidence of clinical benefit in 3 of 4 patients with greater than 100 days of follow-up."

Traditionally, CD19 has not been considered a target for treatments in multiple myeloma, due to low levels of expression on dominant cells. However, the researchers hypothesized that CD19-positivity on minor subsets and very low levels of CD19 expression on the dominant cells could be ample to elicit responses.

In the ongoing study, patients received high-dose melphalan with autologous stem cell transplantation (ASCT) followed 12 to 14 days later by an infusion of 1 to 5x107 cells of CTL019. All patients had progressed within 1 year of receiving prior ASCT (range 100-342 days). The primary endpoints of the study were safety and feasibility, with secondary outcome measures focused on response, CTL019 expansion, and in vivo activity.

At the time of the analysis, 5 patients were evaluable with greater than 60 days since treatment. Two additional patients had received CTL019 <3 weeks before the analysis and 3 patients were awaiting treatment. The majority of the patients had high-risk features (complex karyotype) and had received several prior lines of therapy (range 2-10).

"Interestingly—and the patients were not selected on this basis—on evaluation by immunophenotyping we found some degree of CD19 expression in these patients malignant plasma cells," Garfall noted.

In the study, all but 1 patient responded to treatment with CTL019 (overall response rate = 80%). Response consisted of 1 stringent complete response (sCR) with MRD-negativity at a 339-day follow-up. Other responses included a partial response (PR) and a very good PR (VGPR). One patient experienced an unconfirmed CR with MRD-positivity; however, this patient progressed after 6 months.

"The day 12 to 14 time point at the dose we chose is associated with only transient CTL019 engraftment. We think that prolonging persistence of these cells could lead to improved outcomes," Garfall said. "We are considering amending the protocol to permit serial infusions at later time points that might improve persistence."

The patient experiencing a stringent CR had received 10 prior therapies, including vorinostat, elotuzumab, proteasome inhibitors, and immunomodulatory agents. This individual was 48 year-old female with a complex karyotype, t(4;15), TP53 deletion, and +1q.

For this patient, treatment with CTL019 caused a rapid decline in immunoglobulin and by day 130 she met the criteria for a stringent CR, explained Garfall. "This was obtained despite the fact that the overwhelming majority of plasma cells were negative for CD19 using sensitive techniques," he added.

No significant toxicities were observed with CTL019 in the study. There was one episode of grade 1 cytokine release syndrome observed. Transient hypogammaglobulinemia was observed.

"We've observed no significant toxicity attributable to CTL019," Garfall said. "We've had only one manufacturing failure, so the manufacturing of CAR T cells in this patient population seems feasible."

CTL019 has demonstrated promising efficacy across a number of settings for patients with hematologic malignancies, including those with acute lymphoblastic leukemia (ALL). In July 2014, CTL019 received a breakthrough therapy designation from the FDA as a potential treatment for pediatric and adults patients with relapsed/refractory ALL.

The personalized adoptive cell therapy, which is being developed through an agreement between the University of Pennsylvania and Novartis, elicited a 92% CR rate in pediatric patients with ALL, according to findings presented at the 2014 ASH Annual Meeting.

Ongoing studies are assessing CTL019 in patients with diffuse large B-cell lymphoma, adult and pediatric patients with ALL, and other CD19-positive lymphomas. Additionally, the study presented at ASCO exploring CTL019 in multiple myeloma remains ongoing (NCT02135406).


Garfall AL, Maus MV, Lacey SF, et al. Safety and efficacy of anti-CD19 chimeric antigen receptor (CAR)-modified autologous T cells (CTL019) in advanced multiple myeloma. J Clin Oncol. 2015;33 (suppl; abstr 8517).

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