February 3, 2022 — Two patients with chronic lymphocytic leukemia who 10 years ago were among the first to receive a breakthrough new therapy were still in remission a decade later. .
The treatment, known as CAR T, “may actually cure leukemia patients based on these findings,” lead author Carl H. June, MD, said in a press briefing on the study. , which was published this week in Nature.
Apart from the disappearance of the cancer from the patients, the scientists were also delighted to find that CAR T cells are still present in the blood of the patients.
In CAR T-cell therapy, patients’ own T cells are removed, reprogrammed in a lab to recognize and attack cancer cells, and then reinfused into patients. It has transformed the treatment of various blood cancers and shows often remarkable results in leading to remission.
While treatment has become routine therapy for some leukemias, long-term results on cell fate and function over time are eagerly awaited.
The study details how the two patients were first treated in 2010 at the University of Pennsylvania in Philadelphia
Speaking at the press conference, one of the patients, Doug Olson, described how several weeks after his treatment in 2010 he became very ill with what has become known as the common short-term side effect. cytokine release syndrome, an overreaction of the immune system.
However, after Olson recovered a few days later, Porter gave him the remarkable news that “we can’t find a single cancer cell. You seem completely free to [leukemia].”
Unfortunately, the other LLC patient, Bill Ludwig, who was the first to receive the CAR T-cell treatment, died in 2021 from COVID-19.
A decade after starting treatment, CAR T cells remained detectable in both patients, who had been in remission since their first year of treatment.
“The killer T cells did the initial heavy lifting of eliminating the tumor,” first author J. Joseph Melenhorst, PhD, said in an interview.
Melenhorst established the lab at the University of Pennsylvania to monitor patients treated with CAR T-cell therapy. “[This] the delayed phase of the immune response against cancer is a new idea, and we were surprised to see it.
Another promising result: When Olson returned his cells to the center after more than 9 years, researchers discovered that his cells were still capable of destroying leukemic cells in the laboratory.
“Ten years [post infusion]we can’t find any of the leukemia cells and we still have the CAR T cells patrolling and monitoring residual leukemia,” June, director of the Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, said during the briefing.
Similar effects in other blood diseases?
CAR T-cell therapy is approved in the United States for several blood cancers, and it remains to be seen whether similar long-term cell patterns can be seen in other patients and cancer types, Melenhorst says.
While the prospect of some patients being “cured” is exciting, responses to therapy have generally been mixed. In leukemia patients, for example, complete remissions have been maintained in about 25% of patients, with higher rates in some lymphomas and in pediatric patients. said Melenhorst.
The effects of CAR T-cell therapy in solid cancers have so far been more disappointing, with no studies replicating the kinds of results seen with blood cancers.
“There seem to be a number of reasons, including that the [solid] the tumor is more complex and these solid cancers have ways of evading the immune system that need to be overcome,” June said.
And despite the most encouraging findings about blood cancers, even with these, “the biggest disappointment is that CAR T-cell therapy doesn’t work all the time. It doesn’t work for all patients,” co-author David Porter, MD, the University of Pennsylvania oncologist who treated both patients, said at the press conference.
“I think the importance of Nature study is that we’re starting to learn the mechanics of why and how it works, so we can start to understand how to make it work for more people.” Porter said. “But what we’re seeing is, when it works, it’s really beyond what we expected 10 or 11 years ago.”