All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.
Introducing
Now you can personalise
your AML Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe AML Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the AML Hub cannot guarantee the accuracy of translated content. The AML Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
Bookmark this article
Gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody conjugated to calicheamicin, is approved for newly diagnosed and relapsed/refractory CD33+ acute myeloid leukemia (AML). Results from the phase III ALFA-0701 trial (NCT00927498) showed improved survival rates with fractionated-dose GO plus standard chemotherapy compared with standard chemotherapy alone. However, treatment with GO has been associated with veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly when administered prior to hematopoietic stem cell transplant (HSCT).
VOD/SOS is a serious complication in patients undergoing HSCT and is thought to be a result of hepatic sinusoidal damage following conditioning therapies. More information and expert safety recommendations on GO use and VOD/SOS can be found on the AML Hub. Cécile Pautas and colleagues conducted a retrospective analysis of patients in ALFA-0701 who received HSCT as follow-up therapy and examined post-transplant outcomes and rates of VOD/SOS. Their findings are published in Bone Marrow Transplantation1 and are summarized below.
In ALFA-0701, 271 patients with untreated de novo AML were randomized to 3+7 induction with daunorubicin on Days 1–3 and cytarabine on Days 1–7, with or without GO 3 mg/m2 on Days 1–4. Subsequently, patients who achieved complete remission (CR) after induction received two consolidation courses of daunorubicin and cytarabine with or without GO on Day 1. Apart from patients with core-binding factor AML or with normal karyotype and either NPM1+/FLT3-ITDwt or CEBPA+ AML, patients who had obtained CR were allowed to progress to allogeneic HSCT (allo-HSCT). Endpoints were overall survival, post-HSCT survival, non-relapse mortality, and relapse.
Overall, 85 patients progressed to HSCT, of which 32 were initially randomized to receive GO plus standard chemotherapy and 53 initially received standard chemotherapy alone (controls). Following induction, eight patients in the control arm received GO as follow-up therapy prior to HSCT, and one patient in the GO arm proceeded to HSCT without GO. Baseline and transplant characteristics were similar between arms and are listed in Table 1.
Table 1. Patient characteristics*
Allo-HSCT, allogeneic HSCT; auto-HSCT, autologous HSCT; CR, complete remission GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplant. |
||
Characteristic |
GO |
Control |
---|---|---|
Median age, years (range) |
60 (51–67) |
59 (50–69) |
Male, % |
46.9 |
45.3 |
Cytogenetics, % |
|
|
Median time from last GO dose to HSCT, days (range) |
222 (64–1,215) |
121 (52–753) |
Time of HSCT relative to last GO dose, % |
|
|
Timing of HSCT, % |
|
17.0 |
Transplant type, % |
|
|
Conditioning type, % |
|
|
Complete remission was achieved by 29 patients in the GO arm and 44 patients in the control arm, with a median time from first CR to HSCT of 6.4 months and 7.8 months, respectively. Three patients developed VOD/SOS prior to HSCT:
Out of 39 patients who received GO prior to HSCT, the rate of VOD/SOS following HSCT/conditioning was 7.7% (n = 3).
Post-transplant outcomes are shown in Table 2. Post-transplant survival, non-relapse mortality, and relapse rate were similar between the GO and control arms. Treatment with GO was not associated with a difference in overall survival in patients who received HSCT (HR, 0.97; 95% CI, 0.54–1.75; p = 0.919), however in patients who did not receive HSCT, survival was prolonged in the GO arm compared with the control arm (HR, 0.68; 95% CI, 0.48–0.97; p = 0.0333).
Table 2. Post-transplant outcomes*
CI, confidence interval; CR, complete remission; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplant; NE, not estimable; NRM, non-relapse mortality, OS, overall survival. |
||
Outcome |
GO |
Control |
---|---|---|
Median OS, months (95% CI) |
21.4 (9.4–NE) |
17.1 (7.3–NE) |
3-year survival, % (95% CI) |
39.4 (21.9–56.5) |
44.5 (30.5–57.6) |
12-month NRM, % (95% CI) |
28.7 (14.1–45.2) |
21.6 (11.5–33.8) |
12-month relapse rate, % (95% CI) |
9.4 (2.3–22.6) |
31.4 (19.1–44.4) |
Median post-transplant survival, months (95% CI) |
n = 17 |
n = 22 |
3-year survival post-transplant, % (95% CI) |
n = 15 |
n = 31 |
Fractionated-dose GO, as part of induction and consolidation chemotherapy for AML, was shown not to induce excess post-transplant VOD/SOS or mortality, with the rate of post-HSCT/conditioning VOD/SOS in patients exposed to GO similar to other retrospective analyses. The authors suggested that the low rate of VOD/SOS in their study may be due to the use of fractionated-dosing, reduced-intensity conditioning in the majority of patients, and the 2-month interval between the last GO dose and HSCT. They therefore proposed that treatment with fractionated-dose GO does not rule out the use of HSCT as a consolidation therapy option.
Your opinion matters
Subscribe to get the best content related to AML delivered to your inbox