February 11, 2021 - A conditioning regimen comprised of targeted radiation with Iomab-B led to a lower incidence of sepsis as well as trends toward reduced rates of severe mucositis and febrile neutropenia versus conventional care and standard conditioning regimens in older adults with relapsed or refractory acute myeloid leukemia.
A condition regimen comprised of targeted radiation with Iomab-B led to a lower incidence of sepsis as well as trends toward reduced rates of severe mucositis and febrile neutropenia versus conventional care and standard conditioning regimens in older adults with relapsed or refractory acute myeloid leukemia (AML), according to data from the phase 3 SIERRA trial (NCT02665065) that were presented during the 2021 Transplantation and Cellular Therapy Meetings.
Iomab-B is a radioactive iodine (131I)–labeled anti-CD45 antibody. Patient-specific dosimetry is used to develop an individualized therapeutic dose of the therapy which targets marrow and spares non-hematopoietic organs.
“Targeted radiation with Iomab-B led to relatively low radiation exposure of the [gastrointestinal] tract and a higher radiation exposure of the marrow, resulting in a favorable toxicity and safety profile in older patients with relapsed/refractory acute myeloid leukemia,” Rajneesh Nath, MD, a medical oncologist at the Banner MD Anderson Cancer Center, said in an oral presentation of the data at the meeting.
In this randomized, prospective trial, patients with active, relapsed or refractory AML were randomized 1:1 to receive either Iomab-B with hematopoietic stem cell transplant (HCT) or conventional care. Notably, patients who did not go into remission were allowed to crossover from conventional therapy to the HCT and Iomab-B regimen.
The primary end point of the study was durable complete remission rate (dCR), defined as a complete response (CR) or complete response with incomplete platelet recovery (CRp) at 6 months post-CR. Key secondary end points include overall survival and event-free survival.
With 75% enrolled, a total of 113 patients have been evaluated thus far, including 56 in the Iomab-B arm and 57 in the conventional care arm. Over the course of the study, 30 patients who were randomized to conventional care crossed over to receive Iomab-B with HCT and 10 achieved a CR and crossed over to receive standard HCT alone.
Patients in the Iomab-B plus HCT arm received a total Iomab-B infused dose of 646 (354-1027) mCi with a dose of 14.7 (4.6-32)3 Gy to the marrow. For patients who crossed over to the Iomab-B with HCT combination, they received a total Iomab-B infused dose of 592 (313-1013) mCi with a dose of 15.5 (6.3-42)3 Gy to the marrow.
At day 100, the non-relapse mortality was 4.4% among those in the Iomab-B arm, 20% among those who received standard of care HCT, and 10.7% among those who crossed over to receive Iomab-B plus HCT.
Investigators used post-dosimetry gamma camera imaging to show organ-specific uptake of Iomab-B in order to calculate the total dose delivered to each organ. Overall, it was determined that the therapeutic dose delivered a maximum of 24 Gy to the liver, the dose-limiting organ.
Among all patients studied, the most common non-hematologic grade 3 or 4 adverse events (AEs) observed were febrile neutropenia, sepsis/septic shock, mucositis, pneumonia, hypertension, respiratory failure, hypoxia, catheter-related infection, hypotension, acute kidney injury, and sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD; grade 1 or 2). At day 100 post HCT, AEs of interest included sepsis (2 patients in the Iomab-B arm [4.2%], 3 in the standard HCT arm [30.0%], and 7 who crossed over to Iomab-B/HCT [23.3%]), febrile neutropenia (grade 3-4; 20 [41.7%], 5 [50.0%], and 12 [40.0%], respectively), and mucositis (grade 3-4; 5 [10.4%], 3 [30.0%], and 5 [16.7%]).
“Adverse events were not correlated to the overall radiation dose,” Nath noted.
Nath R, Gyurkocza B, Choe H, et al. Myeloablative targeted conditioning with anti-CD45 Iodine (131I) apamistamab [Iomab-B] spares the GI tract and has low incidence of severe mucositis, febrile neutropenia and sepsis in the prospective, randomized phase 3 sierra trial for patients with relapsed or refractory acute myeloid leukemia (AML). Presented at the Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. Abstract 59.