More Intense ALL Therapy Improves Outcomes in Adolescents, Young Adults

HOUSTON -- Pediatric treatment protocols outperformed standard therapy for adolescents and young adults (AYAs) with Philadelphia chromosome-negative acute lymphocytic leukemia (ALL), a retrospective cohort study showed.

Patients treated with "pediatric-inspired protocols" (PIPs) had a median 2-year event-free survival (EFS) of 80.6% versus 52.6% with hyperCVAD. Median relapse-free survival (RFS) at 2 years was 93.7% with PIPs and 59.6% with standard therapy. The improvement did not extend to 2-year overall survival, although a trend favored the PIP regimens, reported Omar Shahin, MBChB, of King Hussein Cancer Center in Amman, Jordan, at the Society of Hematologic Oncology meeting.

"There was no significant difference in rates of complete remission or allogeneic stem-cell transplantation between the two treatments," said Shahin. "However, the hyperCVAD arm had a higher relapse rate."

During a discussion that followed the presentation, moderator Selina Luger, MD, of the University of Pennsylvania in Philadelphia, asked whether the two treatment groups differed with respect to completion of required therapy. Shahin said patients in both groups were treated to complete remission (CR), at which time they were eligible for allogeneic transplant. Both treatment groups had CR rates of about 93%. In response to another question, Shahin said the hyperCVAD regimen was not augmented with pegaspargase.

ALL affects people of all ages but more often children. In recent years, investigators in the field have identified AYAs as a distinct subgroup, Shahin noted in his introduction to the study. Survival in AYAs (patients ages 15 to 39) is better than adults with ALL, but not as good as children.

The outcome differences between children and AYAs have led to evaluations of PIPs in the age group. In general, PIPs for ALL are more intensive and regimented as compared with regimens used for adults, and the characteristics of the protocols are often credited with the superior outcomes observed in pediatric patients with ALL. Previous retrospective studies have shown that AYAs have similar or better outcomes with PIPs, Shahin continued.

Investigators retrospectively compared outcomes in AYAs treated with a PIP or hyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride [Adriamycin], methotrexate, cytarabine, and dexamethasone) at King Hussein Cancer Center from 2010 to 2022. Patients treated with a PIP received one of three regimens: CALGB 10403, augmented Berlin-Frankfurt-Munster (aBFM), or GRAALL-2005.

The study included 113 patients, 57 who received hyperCVAD and 56 treated with PIPs. The hyperCVAD group was older (median age 27 vs 23), but otherwise the two groups were comparable, said Shahin. Most of the patients had T-cell ALL phenotype, about half had diploid cytogenetics, and 4.4% had high-risk disease.

The cohort had a median follow-up of 24 months, and the primary outcomes were OS, EFS, and RFS. Key secondary objectives included CR rates at the end of induction therapy, relapse rates, and transplantation rates.

Overall, the cohort had a 2-year EFS of 65.8%, and 2-year RFS of 75.6% but both outcomes were significantly improved with PIPs (P=0.004, P=0.0001, respectively). The 2-year OS was 72.2% for the entire cohort, including 80.3% among patients treated with PIPs and 65.7% for those treated with hyperCVAD. As noted, this difference did not achieve statistical significance (P=0.158).

Analysis of secondary outcomes showed that patients in the hyperCVAD group had a significantly higher rate of leukemic relapse (38.6% vs 5.6%, P=0.005). A fourth of all patients underwent stem-cell transplantation, and the rate did not differ significantly by treatment. At last follow-up, 89.1% of patients treated with PIPs remained in CR as compared with 71.9% for hyperCVAD treatment (P=0.004). Two patients died during induction therapy, both treated with PIPs, and 11 patients died in CR, six in the hyperCVAD group and five in the PIP group.

Comment