ISSN 1866-8836
Клеточная терапия и трансплантация

AL-02. Treatment options for adult patients with refractory/relapsed acute myeloid leukemia

Bella I. Ayubova1, Sergey N. Bondarenko1, Ivan S. Moiseev1, Anna G. Smirnova1, Olga S. Uspenskaya2, Elena V. Karyagina3, Evgenia I. Zhelnova4, Elena V. Babenko1, Ildar M. Barkhatov1, Tatyana L. Gindina1, Alexander D. Kulagin1

1 RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
2 Leningrad Regional Clinical Hospital, St. Petersburg, Russia
3 City Hospital No.15, St. Petersburg, Russia
4 City Clinical Hospital No.52, Moscow, Russia


Contact: Dr. Bella I. Ayubova, e-mail: bella_ayubova@mail.ru

doi 10.18620/ctt-1866-8836-2022-11-3-1-132

Summary

Outcomes for patients (pts) with refractory/relapsed acute myeloid leukemia (r/rAML) are dramatic because of the low response rate, which reaches less than 30%. Allogeneic hematopoietic stem cell transplantation (HSCT) as consolidation of second remission improves three-year overall survival (OS) from less than 10% to 50%. By this way, the search for new therapeutic options for pts with r/rAML is relevant so far. Our aim was to evaluate the outcomes after high-dose chemotherapy (HDChT) and immunochemotherapy in adult pts with r/rAML.

Patients and methods

92 pts with median age 34 (18-61) years were included in the analysis. Status of AML before therapy was as follows: relapsed (Rel) n=37, refractory (Ref) n=55. HDChT group included 40 pts treated with “FLAG” with or without anthracyclines – “FLAG” n=17 or “FLAG-Ida/Mito” n=23; another group of 52 pts received “FLAG” with gemtuzumab ozogamicin – “GO-FLAG”. The groups were comparable for age (p=0.56), sex (p=0.31), genetic risk ELN2017 (p=0.97) and AML status (p=0.09). Special feature of “GO-FLAG” pts group were extramedullary disease (ED) in 16 (31%) cases.

Results

Overall response (OR) after HDChT was achieved in 25 (62.5%) pts: complete remission (CR) – 50%, CR with incomplete recovery (CRi/r) – 12.5%. OR after “GO-FLAG” therapy were in 38 (73.1%) pts: CR – 51.9%, CRi/r – 21.2. The less rate OR were observed after “FLAG” 41.2% vs “FLAG-Ida/Mito” 78% (18 out of 23) vs “GO-FLAG” 73.1%, p=0.025. HSCT after HDChT was performed in 25 pts (62.5%), 19 pts were in remission and median time from OR to HSCT was 89 (19-336) days. Subsequent HSCT in the “GO-FLAG” group was performed in 27 pts (51.9%) and 25 pts were in remission, with median time to HSCT was 40 (16-224) days. Median follow-up was 35 (18.4-52.2) months. Two-year OS in the HDChT and “GO-FLAG” groups was 8.7 (95% CI: 5.3 to 16.7) months and 6.4 (95% CI: 4.2 to 8.8) months, respectively (p=0.38). Two-year relapse-free survival: after HDChT-8.5 (95% CI: 4.3-18.3) months, “GO-FLAG”-5.1 (95% CI: 3.0-15.5) months, p=0.08. According to multivariable analysis, the risk of any event (EFS) was decreased after HSCT (HR 0.27; CI95%: 0.19-0.1; p<0.001), after “FLAG-Ida/Mito” (HR 0.2; CI95%: 0.09-0.46; p<0.001) and after “GO-FLAG” (HR 0.23; CI95%: 0.1-0.53; p<0.001), and increased with adverse genetic abnormalities (HR 2.4; CI95%: 1.0-5.5; p=0.048). Analysis of toxicity demonstrated no differences depending on the therapeutic groups. Therapy-related mortality: after HDChT – 10% (causes in 3 pts – cerebral hemorrhagic, 1 pts – sepsis); “GO-FLAG” – 9.6% (3 pts – infections, 1 pts – cerebral hemorrhagic, 1 pts – progression).

Conclusions

The “FLAG”, “FLAG-Ida/Mito”, and “GO-FLAG” demonstrated favorable outcomes in pts with r/rAML. After “FLAG-Ida/Mito” and «GO-FLAG» therapy, there was significant increase in remission rates when compared to “FLAG”. A distinctive feature of “GO-FLAG” was the high response rate in patients with ED. The main predictors favorably influencing EFS were: the choice of “FLAG-Ida” and “GO-FLAG”, subsequent HSCT.

Keywords

Acute myeloid leukemia, target therapy, high-dose chemotherapy, gemtuzumab ozogamicin.



Volume 11, Number 3
10/31/2022

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doi 10.18620/ctt-1866-8836-2022-11-3-1-132

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