CAR T-cell immunotherapy prompts durable response for ALL
CHICAGO — Young patients with extramedullary relapse of acute lymphoblastic leukemia achieved potent and durable responses to single-agent chimeric antigen receptor T-cell immunotherapy, according to data presented at the ASCO Annual Meeting.
Previous data showed anti-CD19 chimeric antigen receptor (CAR) T-cell therapies generated durable marrow responses in patients with relapsed or refractory CD19–positive ALL.
“We as pediatric oncologists do an outstanding job at curing the vast majority of children with newly diagnosed ALL ... [however,] the OS of children with ALL in forced relapse [is in the] 50% to 70% range,” Mala Kiran Talekar, MD, pediatric oncologist at Children’s Hospital of Philadelphia, said during her presentation. “Further, if children suffer a second relapse, this plummets down to a dismal 15% to 20%. Therapies are urgently needed, and here comes the role of CAR T cells as a breakthrough therapy.”
Talekar and colleagues evaluated data from 97 children treated on phase 1/phase 2a clinical trials with CAR T cells and identified 10 who had extramedullary relapse of ALL.
Patients received murine anti-CD19 CAR T cells (CTL019; n = 6) or humanized anti-CD19 CAR T cells (CTL119; n = 4).
Extramedullary relapse occurred a median 2.3 months (range, 0-9) prior to infusion; five patients experienced relapse at time of infusion. These relapses occurred at various sites including testes, sinus, parotid, bone, uterus, kidney and skin; five patients had multiple sites of extramedullary involvement. One patient had isolated extramedullary relapse of parotid and multifocal bony lesions, and another patient had relapse in the testis and sinus.
Patients had experienced two to four relapses of ALL prior to CAR T-cell infusion.
All patients underwent hematopoietic stem cell transplantation — two of whom also received radiation directed to the extramedullary site prior to therapy — prior to extramedullary relapse.
Serial imaging showed five patients had objective responses to CAR T cells — two patients had resolved extramedullary disease at 28 days, two had resolved disease by 3 months, and one patient continued to experience a decrease in size of uterine mass at 3 and 6 months and underwent hysterectomy at 8 months with no evidence of disease.
Four patients had a prior history of skin or testicular involvement, which appeared to resolve through examination after 28 days.
One patient experienced disease progression within 2 weeks of CAR T-cell infusion and died at 6 weeks. Three patients relapsed with CD19–positive disease, including one with skin/medullary involvement who died 38 months after infusion, one with medullary involvement who died at 17 months, and another with medullary involvement who remained alive at 28 months.
At a median follow-up of 10 months (range 3-16), six patients remained alive and without recurrence of disease.
“Single-agent CAR T-cell immunotherapy can induce potent and durable responses in patients with extramedullary relapse of their ALL,” Talekar said. – by Melinda Stevens
Talekar MK, et al. Abstract 10507. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Talekar reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.