Pediatric patients with KMT2A-rearranged acute myeloid leukemia who were treated with gemtuzumab ozogamicin plus standard chemotherapy experienced improved event-free survival and a reduced relapsed risk.
Treatment with gemtuzumab ozogamicin and standard chemotherapy yielded improved outcomes for pediatric patients with KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML), according to results from the phase 3 children’s oncology group trial AAML0531 (NCT01407757) that was published in the Journal of Clinical Oncology; consolidation therapy with hematopoietic stem cell transplant (HSTCT) may yield even better outcomes, investigators said.
At 5 years, the event-free survival (EFS) from study entry was 38% and the overall survival (OS) was 58%. When patients were treated with gemtuzumab ozogamicin had a 5-year EFS 48% compared with 29% in the non–gemtuzumab ozogamicin group (P = .003). However, OS was comparable with 63% in the gemtuzumab ozogamicin group and 53% in the control group (P = .054). A lower relapse risk was seen in 40% of patients who were treated with gemtuzumab ozogamicin compared with 66% of patients who did not receive gemtuzumab ozogamicin (P = .001). An improved 5-year disease-free survival (DFS) rate of 57% was reported among patients in the gemtuzumab ozogamicin group compared with 33% of patients in the non-gemtuzumab ozogamicin group (P = .002).
A total of 1022 patients were enrolled, 21% of whom had KMT2A-r AML. Patients with KMT2A-r were younger and less likely to have clinically relevant co-occurring mutations compared with KMT2A wild-type patients who were more likely to have cytogenic complexity and non-central nervous system extramedullary disease.
The multivariate analysis comparing the KMT2A-r and KMT2A wild-type disease arms, treatment arms, and corresponding interaction term showed a significant interaction term for EFS (P = .022) and DFS (P = .020). This indicates that gemtuzumab ozogamicin may have different treatment effects on the KMT2A wild-type and KMT2A-r AML for EFS and DFS, but not for OS (P = .119) and relapse risk (P = .066).
Patients with KMT2A-r had a higher rate of EOI1 morphologic complete remission after being treated with gemtuzumab ozogamicin (77%) compared with those treated without gemtuzumab ozogamicin (64%; P = .035). Additionally, those treated with gemtuzumab ozogamicin in the KMT2A-r and KMT2A wild-type arms had comparable outcomes regardless of gemtuzumab ozogamicin exposure. Patients with HR translocations who were treated with gemtuzumab ozogamicin had a better EFS (27%; 95% CI, 14%-41%) compared with those who were not treated with gemtuzumab ozogamicin (6%; 95% CI, 1%-18%; P = .013).
The non-HR subset (n = 107) saw an improved EFS of 66% (95% CI, 51%-77%) after being treated with gemtuzumab ozogamicin compared with 42% in those who did not receive gemtuzumab ozogamicin (95% CI, 29%-55%; P = .017). Additionally, DFS was 75% in the gemtuzumab ozogamicin group (95% CI, 59%-86%) compared with 50% in the non-gemtuzumab ozogamicin group (95% CI, 32%-65%; P = .025), and relapse risk was 22% in the gemtuzumab ozogamicin cohort (95% CI, 11%-36%) compared with 47% in the control cohort (95% CI, 29%-63%; P = .026).
Among the 215 patients with KTMT2A-r, 14% received HSTCT in the first CR, 63% of whom received gemtuzumab ozogamicin during the first induction. Patients who had previous gemtuzumab ozogamicin exposure and had received HSCT had a DFS of 72% (95% CI, 45%-87%) compared with 27% (95% CI, 7%-54%) for patients in the non-gemtuzumab ozogamicin group (P = .004). Additionally, patients saw a reduction in relapse risk when receiving gemtuzumab ozogamicin and HSTCT vs the control group (28%; 95% CI, 10%-50% vs 73%; 95% CI, 32%-91%; P = .006).
Pollard JA, Guest E, Alonzo TA, et al. Gemtuzumab ozogamicin improves event-free survival and reduces relapse in pdiatric KMT2A-rearranged AML: results from the phase III children's oncology group trial AAML0531. J Clin Oncol. 2021;39(28):3149-3160. doi:10.1200/JCO.20.03048