IG Budaeva, DV Zaitsev, AA Shatilova, EN Tochenaya, AV Petrov, RI Vabishchevich, DV Motorin, RSh Badaev, DB Zammoeva, VV Ivanov, SV Efremova, KV Bogdanov, YuV Mirolyubova, TS Nikulina, YuA Alekseeva, AYu Zaritskey, LL Girshova
VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341
For correspondence: Irina Garmaevna Budaeva, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(931)351-07-06; e-mail: email@example.com
For citation: Budaeva IG, Zaitsev DV, Shatilova AA, et al. Efficacy, Safety, and Tolerance of Gemtuzumab Ozogamicin Combined with FLAG/FLAG-Ida or Azacitidine in Relapsed/Refractory Acute Myeloblastic Leukemia. Clinical oncohematology. 2021;14(3):299–307. (In Russ).
Aim. To assess the efficacy, safety, and tolerance of gemtuzumab ozogamicin (GO) combined with FLAG/FLAG-Ida chemotherapy or azacitidine in patients with relapsed/refractory acute myeloblastic leukemia (AML) in clinical practice.
Materials & Methods. The study included 32 patients (16 men and 16 women). The median age was 44 years (range 23–83 years). Among them there were 15 (46.8 %) patients with refractory and 17 (53.2 %) patients with relapsed AML. GO combined with FLAG/FLAG-Ida was administered to 15 (46.8 %) patients, whereas 17 (53.2 %) patients were treated with GO and azacitidine combination. Therapy safety was assessed according to CTCAE v. 5.0.
Results. Overall response rate including complete remission (CR), CR MRD–, CR with incomplete hematologic recovery, and morphologic leukemia-free status was 59.4 % (19/32). Refractoriness was observed in 31.25 % (10/32) of patients. Early mortality was 9.4 % (3/32). Overall response was 64.7 % (11/17) in the azacitidine and 53.3 % (8/15) in the FLAG/FLAG-Ida groups. In 4 (80 %) out of 5 patients with prior to FLAG treatment refractoriness, the response was achieved after GO + azacitidine therapy. In 58.9 % (10/17) of patients who received GO + azacitidine therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be performed. The incidence of GO infusion complications in the tested groups did not significantly differ (p = 0.72) and was 46.7 % (7/15) (40 % with grade 1/2 and 6.7 % with grade 3) in the GO + FLAG/FLAG-Ida group and 35.3 % (6/17) (29.4 % with grade 1/2 and 5.9 % with grade 4) in the GO + azacitidine group. In the GO + FLAG/FLAG-Ida group 5 (33.3 %) patients experienced serious adverse events (SAE) of sepsis. In the GO + azacitidine group SAEs were reported in 6 (35.3 %) patients: 4 (66.6 %) with sepsis, 1 (16.7 %) with acute cardiovascular failure, and 1 (16.7 %) with acute respiratory failure. The median (range) duration was 23 (10–39) days for neutropenia grade 4, 24 (11–38) days for neutropenia grade 3, 21 (11–41) days for thrombocytopenia grade 4, 26 (16–45) days for thrombocytopenia grade 3, and 25 (22–45) days for thrombocytopenia grade 1/2. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy, however, no significant differences were identified. No cases of veno-occlusive liver disease were reported. Median overall survival (OS) for both groups (n = 32) was 31.4 months, median disease-free survival (n = 21) was 13.3 months. In the group of patients with effective treatment, the median OS was not reached. In non-responders, it was 18 months (p = 0.0442).
Conclusion. GO combined with FLAG/FLAG-Ida chemotherapy or azacitidine proved effective in relapsed/refractory AML patients. Remission did not appear to be associated with ELN risk, gender, age, CD33 expression, number of prior therapy lines, or number of relapses. GO + azacitidine combination showed efficacy, safety, and good tolerance in patients with prior high-dose chemotherapy refractoriness as well as low ECOG performance status. That allowed for the subsequent allo-HSCT administration to these patients. There was no significant difference between the groups of patients in the incidence of hematologic, non-hematologic toxicity, and time to hematologic recovery. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy which is consistent with literature data. GO-based effective treatment in relapsed/refractory AML considerably improves OS: during 36 months of follow-up the median was not reached.
Keywords: acute myeloblastic leukemia, relapse, refractoriness, gemtuzumab ozogamicin, FLAG/FLAG-Ida regimens, azacitidine, efficacy, safety, toxicity.
Received: February 5, 2021
Accepted: May 15, 2021Статистика Plumx английский
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