Acute lymphoblastic leukemia (ALL), the most common childhood cancer, represents many “firsts” in hematology. It was the first leukemia cured with multiagent chemotherapy and the first disease for which chimeric antigen receptor T-cells (CAR Ts) were an approved therapy. Despite the success achieved in treating this disease, there is still a notable difference in survival by age and a striking difference in prognosis based on race. The pediatric ALL abstracts at this year’s meeting reflect these unique characteristics of ALL.
Hispanic and non-Hispanic Black patients with ALL have worse outcomes compared to non-Hispanic white patients. Prior research demonstrated that Hispanic patients with ALL are more likely to have aggressive disease features. Additionally, lower socioeconomic status of these patients contributes to worse outcomes. It is vital we understand the factors that impact outcomes in these patients so we can resolve these barriers. Several abstracts at the 2021 ASH Annual Meeting report on the racial, ethnic, and socioeconomic factors affecting outcomes in children with ALL.
Abstract 211, “Racial, Ethnic, and Socioeconomic Factors Result in Disparities in Outcome Among Children with Acute Lymphoblastic Leukemia Not Fully Attenuated By Disease Prognosticators: A Children’s Oncology Group (COG) Study,” by Dr. Sumit Gupta and colleagues was one of the largest cooperative group efforts (24,979 patients) to identify inequities by race/ethnicity and socioeconomic status in childhood ALL. The socioeconomic status was assessed by insurance status. A substantial difference in five-year event-free survival was demonstrated in non-Hispanic Black patients (81.9%) and Hispanic patients (82.8%) compared to non-Hispanic white patients (87.4%). Furthermore, U.S. patients with Medicaid had worse five-year survival rates compared to U.S. patients with other insurances (90.3% vs. 92.5%). The poor survival rates were independent of disease characteristics in non-Hispanic Black patients and U.S. patients with Medicaid. Dr. Anurekha Hall and colleagues (abstract 339) also noted the barriers of socioeconomic status in access to care. They compared the demographics of 222 patients with relapsed/refractory (R/R) ALL who were referred to five large pediatric hospitals for CAR-T therapy to those who were receiving CAR-T therapy locally. The authors found that only 28.9 percent of the patients who were referred for CAR-T therapy were Latinx, while 56.3 percent of patients who were treated locally with CAR-T therapy were Latinx.
During this year’s meeting we have witnessed many advancements in CAR-T therapy, and this success is also seen in the pediatric space. Dr. Samuel John and colleagues (abstract 428) presented the real-world outcomes (from the Center for International Blood and Marrow Transplant Research [CIBMTR] registry) of 451 pediatric patients with R/R ALL who were treated with tisagenlecleucel, a CD19-directed CAR-T. The complete response (CR) rate was 87.3 percent with a median duration of response of 23.9 months. Reassuringly, the overall efficacy and safety profile of commercial tisagenlecleucel was similar to that observed in clinical trials. Dr. Chiara Magnani and colleagues (abstract 472) presented treatment outcomes of 26 patients with B-cell ALL who relapsed after allogeneic stem cell transplantation with donor-derived anti-CD19 CAR-Ts. The CAR-Ts were manufactured using a Sleeping Beauty transposon to engineer T cells differentiated according to a cytokine-induced killer (CIK) cell protocol (a non-viral method in contrast to commercial CAR-T products). Among the 26 patients who were enrolled, 21 patients were infused with donor-derived anti-CD19 CAR-Ts. CR was observed in 13 of 21 patients, and the donor type did not influence the CR rate. None of the patients experienced graft-versus-host disease. Some of the responses were durable, with 10 patients remaining in CR at a median follow-up of 21.6 months.
Successful development of CAR-Ts for T-cell ALL (T-ALL) has remained challenging owing to the shared expression of target antigens between CAR-Ts and T-ALL blasts resulting in CAR-T fratricide. Dr. Junfang Yang and colleagues (abstract 473) report data from CD7-targeting CAR-T therapy for R/R T-ALL. A total of 14 heavily pre-treated patients were infused with anti-CD7 CA- Ts. Remarkably, 13 of 14 patients achieved CR or CR with incomplete hematologic recovery, and all 13 patients achieved minimal residual disease negativity as their best response. Only one patient experienced neurotoxicity. Follow-up is short (median follow-up of 105 days); however, this study proves that T-ALL can be successfully treated with CAR-Ts.
Finally, novel combination therapies expand the treatment options for patients with R/R ALL. Dr. Andre Baruchel and colleagues (abstract 516) discussed the addition of isatuximab, an anti-CD38 antibody, in combination with standard relapse chemotherapy regimens, for patients with R/R T- and B-ALL and acute myeloid leukemia. In the phase II study, 24 patients who were heavily pre-treated were enrolled. Among 23 patients who had CD38 evaluated, 21 patients had detectable CD38 expression. A total of 17 patients had evaluable response; 41.2 percent achieved CR.
Finally, for readers who are craving more pediatric updates, an Education Spotlight Session “The Ups and Downs of Therapy for Children with Trisomy 21 and Acute Leukemia,” led by Dr. Rabin, is available on the virtual platform.
Drs. Jeong and Goodman indicated no relevant conflicts of interest.