FDA-approved drugs for relapsed acute lymphoblastic leukemia have remission rates under 25%; experimental therapeutic CAR T cells top that at 90%.
The American Society for Hematology (ASH) meeting, Dec 6-9, 2014, in San Francisco, drew a global crowd. Cancer immunotherapy seemed to be the topic of discussion. We covered two cancer immunotherapy treatments in recent blogs - immune checkpoint inhibitors and CAR T cells.
Several groups at ASH presented data on CAR T cells as therapy for different blood cancers. Results were “incredible” for these studies, as they are for studies that have moved further along and culminated into medical publications. Take the recent clinical trial report on CAR T cells for acute lymphoblastic leukemia (ALL), for example.
ALL has a high cure rate in children, but the relapsed and refractory (treatment-resistant) disease remains the leading cause of death amongst childhood cancers. Adults have poor prognosis to start, and this worsens with relapses and refractory disease progression.
In a phase I/IIa study, 25 patients enrolled in a pediatric trial and 5 in an adult trial. All patients were considered to have incurable conditions; 3 patients had refractory disease, and 27 patients had relapsed disease. Eighteen of those 27 had relapsed after stem cell transplantation therapy.
This study evaluated “CTL019” therapeutic CAR T cells. Patients underwent leukapheresis whereby their blood was drawn and lymphocytes (white cells) were isolated. The isolated lymphocytes were engineered in the lab to enable the expression of anti-CD19 antibody (chimeric antigen receptor) on the surface of T cells. Then, patients received their CTL019 T cells back, now armed to kill CD19-positive ALL cells.
While all patients were at an ALL disease state categorized as incurable, 90% of the patients (27 out of 30) had a response to CTL019 T cells, and were in complete remission at 1 month post infusion of T cells. Follow-up periods for patients ended anywhere from 2 to 24 months, and, at last follow-up, 19 of the 27 patients remained in remission. At 6 months, the event-free survival rate was 67%.
To put this data into perspective, the most recent FDA-approved drugs for relapsed ALL have rates of remission that are less than 25%, with a median documented duration of response from 4 to 9 weeks. The impact of CTL019 therapeutic CAR T cells is therefore “incredible”, with a 90% remission rate and documented patient follow-up periods out to 24 months.
Therapeutic CAR T cells do have a toxic side-effect due to excessive cytokine release from the expansion and proliferation of T cells. In this study, an interleukin-6 receptor blocking drug was incorporated into the management regimen for cytokine release syndrome by therapeutic T cells.
We look forward to further innovations in CAR T cells at the next ASH meeting, even as we continue to follow developments in medical journals. At HemaCare, we provide T cells for research and applaud all bench-to-bedside translations.
1: Maude SL, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17.