Phase III SIERRA Trial Finds Iomab-B Promising for Relapsed/Refractory AML

Novel re-induction and anti-CD45–targeted conditioning with Iodine (131I) apamistamab [Iomab-B] plus allogeneic hematopoietic cell transplantation (HCT) may be a safe alternative to conventional care for older patients with active relapsed/refractory acute myeloid leukemia (AML), according to the results of the phase III SIERRA trial, presented at the Transplantation & Cellular Therapy Meetings of the American Society for Blood and Marrow Transplantation and the Center for International Blood & Marrow Transplant Research (LBA3).

Iomab-B therapy was well-tolerated and produced no grade 3 or 4 infusion-related reactions. In addition, all patients treated with Iomab-B engrafted with majority full donor chimerism by day 100, the researchers found.

Due to lack of efficacy, patients 55 years of age or older with active relapsed/refractory AML who failed standard induction therapies do not usually undergo allogeneic HCT. The investigators conducted this prospective, randomized, phase III, open-label, multicenter, ongoing trial to address this unmet need.

Patients ≥ 55 years with active relapsed/refractory AML were randomized to receive either receive Iomab-B therapy followed by fludarabine 30 mg/m² for 3 days and 2 Gy of total body irradiation and HCT or conventional care. Patients who receive conventional care are given chemotherapy with approved targeted agents and proceed to standard-of-care HCT if complete remission is achieved. Patients who do not achieve complete remission are permitted to cross over to Iomab-B therapy.

Data was presented on the first 38 patients (median age, 63 years) enrolled as of July 5, 2018. All patients had active disease, and 79% did not achieve a complete response in the conventional care arm (67% of patients crossed over to receive Iomab-B). The researchers found that the time-to-transplant in the Iomab-B arm was significantly shorter (28 days vs 67 days in patients proceeding to standard-of-care HCT after complete response). The study showed that the crossover patients had no increase in time to HCT compared with those who underwent a standard-of-care HCT.

Febrile neutropenia (34.2%), stomatitis (15.8%), malnutrition (13.2%), epistaxis (10.5%), sepsis, (10.5%) hypotension (10.5%), hyperbilirubinemia (10.5%) and fatigue (10.5%) were the most common nonhematologic adverse events ≥ grade 3 occurring in more than 10% of patients. No Iomab-B–related deaths were reported, and the 100 day transplant-related mortality rate was 0% in the Iomab-B therapy arm, 10% in the crossover arm, and 25% in the standard-of-care HCT arm.

“Historically in this patient population, access to transplant is approximately 20%, similar to what was achieved for the control arm in this study. However, access to HCT in the study population was 84%, including all transplanted patients (Iomab-B, Crossover and SOC HCT),” concluded the authors.

Iomab-B, via the monoclonal antibody BC8, targets CD45, which is an antigen widely expressed on leukemia and lymphoma cancer cells, B cells, and stem cells. BC8 is linked to the radioisotope iodine-131 and, once attached to its target cells, emits energy that travels a relatively long distance. The investigators theorize that Iomab-B can help avoid the side effects of radiation on most of the healthy tissue while still effectively killing the patient's cancer and marrow cells by carrying iodine-131 directly to the bone marrow in a targeted manner.

“Because it involves a radioactive antibody, the referral, coordination, and timing pre-transplant, it can be very tricky. Planning needs to occur months in advance to make sure things go smoothly,” said study investigator George Chen, MD, who is an associate professor of oncology at Roswell Park Comprehensive Cancer Center.

Margaret T. Kasner, MD, an associate professor and director of the acute leukemia program at Sidney Kimmel Cancer Center at Thomas Jefferson University, said that although the numbers in this study are small, the findings are promising.

“There has been few therapeutic options, but that has changed. So, figuring out where this one fits in will be a little more challenging, but from a safety standpoint it looks great. From an efficacy standpoint, it appears very promising,” Kasner said in an interview with Cancer Network.

However, she said, these findings are preliminary, and much longer follow-up will be required. “It is limited in what they reported, but the side effect profile looks fine. It is in line with other agents and certainly not anything worse,” said Kasner.