ASCO Reading Room | Theodore Laetsch, MD, on risk factors for AYA ALL patients receiving CAR T-Cell therapy

0

Young adults with B-cell acute lymphoblastic leukemia (ALL) with a high disease burden are a high-risk population who may benefit from additional interventions to improve outcomes following chimeric antigen receptor T-cell therapy ( CAR), according to a real-world study.

In an attempt to understand the variables affecting outcomes, Liora Schultz, MD, of Stanford University in California, and her colleagues created a national consortium to enable cross-institutional reporting and analysis. In addition to the overall results, the team reported data on response, toxicity and survival, stratified by disease burden. The results, published in the Journal of Clinical Oncologyshowed that patients with a high disease burden had poorer outcomes, with 12-month overall survival (OS) rates of 58% and event-free survival (EFS) of 31% compared to patients classified as having a high disease burden. low disease burden (85% OS, 70% EFS) or with undetectable disease (95% OS, 72% EFS).

In the following interview, Theodore W. Laetsch, MD, who directs both the Developmental Therapy Program and the Very Rare Malignant Tumors Program at Children’s Hospital of Philadelphia, discussed details of the study of the team, which is the first analysis of commercial tisagenlecleucel stratified by disease burden.

What does the study bring to literature?

Laetsch: Several studies, including ours, have now shown that children and young adults treated in the real world have, on average, a lower burden of disease than patients treated in the clinical trials that led to the approval of tisagenlecleucel. . We knew that patients with lower disease burden had less toxicity with CAR T-cell therapy, but the impact of disease burden on efficacy was unclear. While a decrease in disease burden could obviously be a good thing, there was concern that there was not enough leukemia to cause CAR T cells to grow and persist to control the disease in the long term.

In this study, we found that outcomes are better for children with a low disease burden than for those with a higher disease burden. Specifically, the patient’s risk of leukemia relapse after treatment is lower in patients with low disease burden and OS is better for those with low or undetectable disease compared to those with low disease burden. disease is high. We also confirmed what was already known, that the risk of severe cytokine release syndrome was much lower in people with low disease burden.

Were there any surprises in the data?

Laetsch: The biggest surprise in the data was the impact of disease burden on outcomes. We did not originally start this research to specifically investigate this issue. We sought to report the outcomes of patients treated with commercial tisagenlecleucel in the real world soon after FDA approval. Our initial goal was to see how these results compared to those of the trial that led to the approval. The impact of disease burden was striking in the initial analysis of our data and led us down this path.

How could high disease burden patients be converted into low disease burden patients?

Laetsch: We don’t yet know if it is really disease burden that impacts outcomes, or if disease burden is simply a reflection of underlying biological differences in patients’ leukaemias. It could be that patients with the most treatment-refractory leukemia have a higher disease burden because their leukemia does not respond as well to chemotherapy as it does to CAR T-cell therapy. These same biological factors could make leukemia less responsive to CAR T-cell therapy. In this case, even if we could reduce the disease burden, it might not affect patient outcomes.

Alternatively, results may really be determined by disease burden and patients could receive more intense therapy before CAR T-cell therapy to reduce their disease burden. The downside of more intense therapy is that there is a greater risk of side effects, some of which can be serious or life-threatening. Serious side effects could prevent the patient from receiving CAR T-cell therapy. Further studies are needed to assess whether more therapy to reduce disease burden before CAR T-cell therapy will improve outcomes.

Are other studies planned in this area?

Laetsch: This study was retrospective and collected real-world data from a large number of hospitals. While this is a strength, it is also a limitation, as not all hospitals/physicians assessed disease burden at the same times and in exactly the same way. As noted, studies are needed to determine whether additional therapy before CAR T-cell therapy can reduce disease burden and improve outcomes. In addition, it will be important to continue evaluating the role of stem cell transplantation after CAR T-cell therapy, especially for patients with high disease burden.

What is the basic message for the practicing oncologist?

Laetsch: I encourage oncologists to consider CAR T therapy early in the disease course for patients with relapsed and refractory ALL. Hopefully we can achieve better outcomes for our patients by treating them before their leukemia becomes so unresponsive that it cannot be controlled.

Read the study here and expert commentary on it here.

Laetsch reported personal or institutional financial relationships with Novartis, Bayer, Cellectis, Aptitude Health, Clinical Education Alliance, Deciphera, Jumo Health, Massive Bio, Med Learning Group, Medscape, Physicians’ Education Resource, Y-mAbs Therapeutics, Pfizer, AbbVie , Amgen, Atara Biotherapeutics, Bristol Myers Squibb, Lilly, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Novella Clinical, Servier, Foundation Medicine and Merck Sharp & Dohme.

Share.

About Author

Comments are closed.