Total body irradiation (TBI) regimen and myeloablative transplantation followed by a graft-versus-host disease (GVHD) prophylaxis regimen resulted in a low occurrence of GVHD in adult and pediatric patients with hematologic malignancies
Myeloablative transplantation with a total body irradiation (TBI) preparative regimen, followed by a graft-versus-host (GVHD) prophylaxis regimen results in a decreased incidence of chronic GVHD in adult and pediatric patients with hematologic malignancies, according to data presented at the 2022 Transplantation & Cellular Therapy Meetings.1
In the phase 2 trial, 63 patients were treated with TBI or busulfan (Busuflex) followed by a GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil (MMF) following allogeneic hematopoietic cell transplantation (HCT). The primary end point was cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment at 1 year after transplant.
At 1 year of follow-up, only 2 patients (0.031%) developed chronic GVHD requiring immune suppression; 1 patient in the MRD group and 1 patient in the MUD group, both of whom received peripheral blood stem cell graft.
Following HCT, investigators employed a myeloablative conditioning regimen of TBI at a total dose of 1320 cGy administered twice daily from days -4 to -1. Patients who were unable to receive further radiation received busulfan 3.2 mg/kg daily for a cumulative area under the concentration time curve of 19,000 to 21,000 µmol/min/L plus fludarabine 160 mg/m2 on days -5 to -2. Patients then underwent a GVHD prophylaxis regimen consisting of PTCy (50 mg/kg on days 3 and 4), tacrolimus (beginning at day 5), and MMF (beginning at day 5).
Most patients in the analysis were males (52%) and were over the age of 18 (83%). The median age of patients included in the analysis was 36 (range, 2-55) and the median follow up was 502 days post-HCT.
Patients had a comorbidity by the HCT-comorbidity index of low, intermediate, or high at a rate of 46%, 37%, and 17%, respectively. The most common diagnoses included acute lymphoblastic leukemia (38%), acute myeloid leukemia (35%), and myelodysplastic syndromes (11%).
All 63 patients achieved primary neutrophil engraftment by 42 days, with a median of 16 days (range, 13-27). Almost all patients (94%) experienced platelet engraftment by 6 months, with a median of 25 days (range, 16-98). By day 100, 86% of patients had achieved full donor bone marrow chimerism and 95% had achieved full donor peripheral blood CD3 and CD33 chimerism (both defined as > 95% donor DNA).
Further results from the study showed that the overall cumulative incidence of grade 2-4 active GVHD by 100 days post-transplant was 14% overall (95% CI, 6%-23%), including 7% in the MRD group and 32% in the MUD group. The incidence of grade 3/4 acute GVHD was 5% (95% CI, 0%-10%) and was found to be similar in both the MRD and MUD arms.
The estimated 2-year overall survival rate was 79% (95% CI, 65%-88%), with a 75% rate in the MRD group and a 95% rate in the MUD group. The estimated 2-year GVHD-free relapse survival rate was 57% (95% CI, 42%-69%), 56% in the MRD group and 63%, in the MUD group.
The 2-year cumulative estimated incidence of relapse was 22% in the MRD arm and 16% in the MUD arm, for a total of 21% overall. Finally, the 2-year cumulative incidence of non-relapse mortality was 13% overall, with a 15% and 5% rate in the MRD and MUD groups, respectively.
In terms of safety, 66% of patients needed total parenteral nutrition for oral mucositis and regimen-related toxicities during their initial transplant admission.
Study authors concluded that the regimen was feasible and effective for both adult and pediatric patients. They also added that a further improvement in outcomes could be reached through incorporating post-transplant mitigating strategies with supportive care to combat the toxicities related to the regimen.
Combining Avutometinib With Defactinib Yields High Response Rates in LGSOC
March 22nd 2024In heavily pretreated patients with recurrent low-grade serous ovarian cancer, the combination of avutometinib plus defactinib showing promising results within the phase 2 ENGOT-ov60/GOG-3052/RAMP 201 trial.
Read More
Lachowiez Considers the Use of Tagraxofusp in BPDCN as Bridge to SCT With Peers
March 21st 2024During a Targeted Oncology™ Case-Based Roundtable™ event, Curtis Lachowiez, MD, discussed targeted therapy for blastic plasmacytoid dendritic cell neoplasm and its role in patients who could receive allogeneic stem cell transplant.
Read More
Ixabepilone/Bevacizumab Improves PFS and OS in Platinum-Resistant/Refractory Ovarian Cancer
March 19th 2024Combining ixabepilone with bevacizumab generated improved survival rates and high response rates compared with ixabepilone monotherapy in platinum-resistant or platinum-refractory ovarian cancer.
Read More