Gemtuzumab Ozogamicin Plus Chemo Improves Outcomes in Pediatric KMT2A-Rearranged AML

Pediatric patients with KMT2A rearranged acute myeloid leukemia treated with gemtuzumab ozogamicin plus standard chemotherapy experienced improved event-free survival and reduced risk of relapse.

Treatment with gemtuzumab ozogamicin and standard chemotherapy yielded improved outcomes for pediatric patients with KMT2A rearranged (KMT2A-r) acute myeloid leukemia (AML), according to the results of the Phase 3 Pediatric Oncology Group Study AAML0531 (NCT01407757) published in the Journal of Clinical Oncology ; consolidation therapy with hematopoietic stem cell transplant (HSCTT) may yield even better results, researchers say.

After 5 years, event-free survival (EFS) from study entry was 38% and overall survival (OS) was 58%. When patients were treated with gemtuzumab ozogamicin, a 5-year EFS had 48% compared to 29% in the non-gemtuzumab ozogamicin group (P = 0.003). However, OS was comparable with 63% in the gemtuzumab ozogamicin group and 53% in the control group (P = .054). A lower risk of relapse was seen in 40% of patients treated with gemtuzumab ozogamicin compared to 66% of patients not receiving gemtuzumab ozogamicin (P = 0.001). An improved 5-year disease-free survival (DFS) of 57% was reported in patients in the gemtuzumab ozogamicin group compared to 33% in patients in the non-gemtuzumab ozogamicin group (P = 0.002).

A total of 1022 patients were included, 21% of whom had KMT2A-r AML. Patients with KMT2A-r were younger and less likely to have clinically relevant co-occurring mutations compared to KMT2A wild-type patients who were more likely to have cytogenic complexity and extramedullary non-central nervous system disease.

The multivariate analysis comparing the KMT2A-r and KMT2A wild-type disease arms, treatment arms and the associated 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 = 0.19) and relapse risk (P = 0.066).

Patients with KMT2A-r had a higher rate of EOI1 morphological complete remission after treatment with gemtuzumab ozogamicin (77%) compared to patients treated without gemtuzumab ozogamicin (64%; P = 0.035). In addition, those treated with gemtuzumab ozogamicin in the KMT2A-r and KMT2A wild-type arms had similar results regardless of gemtuzumab ozogamicin exposure. Patients with HR translocations treated with gemtuzumab ozogamicin had better EFS (27%; 95% CI, 14%-41%) compared to those not treated with gemtuzumab ozogamicin (6%; 95% CI, 1% -18). %; P = .013).

The non-HR subgroup (n = 107) saw an improved EFS of 66% (95% CI, 51%-77%) after treatment with gemtuzumab ozogamicin compared to 42% in those who did not receive gemtuzumab ozogamicin (95% CI) . , 29%-55%; P = .017). In addition, the DFS was 75% in the gemtuzumab-ozogamicin group (95% CI, 59%-86%) compared to 50% in the no gemtuzumab-ozogamicin group (95% CI, 32%-65%; P = 0.025), and the relapse risk was 22% in the gemtuzumab ozogamicin cohort (95% CI, 11%-36%) compared to 47% in the control cohort (95% CI, 29%-63%; p = 0.026) .

Of the 215 patients with KTMT2A-r, 14% received HRTCT in the first CR, of whom 63% received gemtuzumab ozogamicin during the first induction. Patients previously exposed to gemtuzumab ozogamicin who 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). In addition, patients saw a reduction in relapse risk when they received gemtuzumab ozogamicin and HRTCT versus the control group (28%; 95% CI, 10%-50% vs 73%; 95% CI, 32%-91%; P = .006) .


Pollard JA, Gast E, Alonzo TA, et al. Gemtuzumab ozogamicin improves event-free survival and reduces relapse in pediatric KMT2A rearranged AML: results of the phase III group study for pediatric oncology AAML0531. J Clin Oncol. 2021;39(28):3149-3160. doi:10.1200/JCO.20.03048

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