Investigators said longer-term outcomes from chimeric antigen receptor (CAR) T-cell therapies are still a significant question in patients who have non-Hodgkin lymphoma (NHL) or acute lymphoblastic leukemia (ALL).
Anti-CD22 chimeric antigen receptor (CAR) T-cell therapies appear to be a useful target in relapsed or refractory (R/R) B-cell malignancies, according to a new meta-analysis.
The FDA has approved 4 CAR T-cell therapies to treat non-Hodgkin lymphoma (NHL). One of those has also been approved to treat acute lymphoblastic leukemia (ALL). All of the approved therapies target the B-lymphocyte antigen CD19.
“The emergence of chimeric antigen receptor T-cell immunotherapy, in which T cells are genetically engineered to express CARs targeting specific tumor-associated antigens, has significantly changed the treatment of these R/R diseases,” wrote the study authors in Frontiers in Immunology.
Yet, while CD19-targeted therapies have been at the forefront of CAR T-cell science, the authors noted that about 30% of patients fail to respond to CD19 CAR T cells and a significant percentage of patients who achieve a complete response will relapse within 1 year (estimates range from 36%-57%). That’s one reason why a growing number of studies have been evaluating CAR T-cell therapies targeting CD22 as well as therapies that dually target CD19 and CD22 in B-cell malignancies, they said.
With all that new research, however, has come the need to systematically consolidate the findings to better understand the potential of the therapies and the risks of common adverse events, such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), the authors said. They noted that previous reviews of CAR T-cell studies have mostly been focused on anti-CD19 therapies or did not include recent trials.
In their new systematic review and meta-analysis, they searched for trials and conference abstracts in which CD22-targeted CAR T-cell therapies were studied in patients with ALL or NHL. The primary outcome was best clinical response (bCR). They found 100 references that met inclusion criteria. Those references included 30 early-phase studies involving 637 patients.
Overall, CD22 CAR T cells had a bCR rate of 68% (95% CI, 53%-81%) in ALL and 64% (95% CI, 46%-81%) in NHL. Most of the patients in the studies (74% of ALL and 96% of NHL) had previously received CD19 CAR T cells, the authors said.
Combination CD19/CD22 CAR T cells had a bCR rate of 90% in ALL (95% CI, 84%-95%) and 47% in NHL (95% CI, 34%-61%), the authors found.
“This systematic review of CD22 CAR T-cell clinical trials observed a strong signal of efficacy and safety of both single (CD22) and dual-target (CD19/CD22) CAR T cells in patients with R/R B-cell malignancies,” they wrote.
In terms of the therapies’ safety profiles, the investigators found an 87% incidence of CRS, but only 6% of patients had cases considered severe (grade 3 and above). Sixteen percent of patients experienced ICANS, and 3% experienced severe ICANS. The authors said that amounted to an acceptable safety profile. In addition, they said there was “no indication” that dual-target CAR T cells led to a greater risk of adverse events compared with single-target therapies.
The authors said longer-term data are needed to better understand whether dual-targeting CAR T cells have improved rates of relapse-free survival.
“Regardless, our study showed that CD22 CAR T cells present another line of therapy for patients who relapse post CAR T-cell therapy with CD19-negative disease,” they said.
The authors said one challenge with an analysis like theirs is that certain characteristics of CAR T-cell therapy are often missing from studies, including information about the therapy’s structure and dosing regimen.
“CAR T cells are highly modular therapies, and preclinical studies have shown that simple modifications (eg, switching costimulatory domain, altering linker length) can have drastic effects on function,” they noted.
The authors encouraged investigators to be more robust and transparent in their CAR T-cell trial registration.
In the meantime, the investigators said the existing data suggest CD22 appears to be a viable antigen target in B-cell malignancies.
Fergusson NJ, Adeel K, Kekre N, Atkins H, Hay KA. A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Front Immunol. Published online April 27, 2023. doi:10.3389/fimmu.2023.1178403