Adding inotuzumab ozogamicin to cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) with sequential blinatumomab is a “safe and highly effective” frontline treatment for Philadelphia chromosome-negative (Ph-negative) B-cell acute lymphoblastic leukemia (ALL), according to a recent phase II study.
Nicholas Short, MD, of the MD Anderson Cancer Center, and colleagues conducted the study and presented its results at the 2022 American Society of Hematology Annual Meeting and Exposition.
They evaluated the safety and efficacy of hyper-CVAD with sequential blinatumomab, with or without inotuzumab ozogamicin, in patients with newly diagnosed Ph-negative B-cell ALL. The study included 62 patients aged 14 to 59 years, with a median patient age of 34 years. More than half (52%) of the patients had at least one high-risk pretreatment characteristic when they enrolled. At enrollment, 14 of the patients were in complete remission, and half of those patients were negative for minimal residual disease (MRD).
Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles, followed by four cycles of blinatumomab at standard doses. Those who had CD20-positive disease received eight doses of ofatumumab 2000 mg or rituximab 375 mg/m2. Patients received eight doses of prophylactic intrathecal chemotherapy.
Patients received maintenance therapy with alternating blocks of blinatumomab and 6-mercaptopurine, vincristine, methotrexate, and prednisone (POMP). They received blinatumomab during maintenance cycles four, eight, and 12. Patients received POMP during maintenance cycles one through three, five through seven, nine through 11, and 13 through 15. Patients who had high-risk disease features began receiving blinatumomab after two cycles of hyper-CVAD. Starting with the 39th patient, the study’s investigators added inotuzumab ozogamicin 0.3 mg/m2 on days one and eight. They also added inotuzumab ozogamicin 0.3 mg/m2 to two cycles of methotrexate plus cytarabine and to two cycles of blinatumomab consolidation.
As of June 2022, 38 patients received treatment without inotuzumab ozogamicin and 24 received treatment with inotuzumab ozogamicin.
All 48 patients who had active disease when they enrolled achieved a complete remission, with 81% of patients achieving a complete remission after the first cycle. Most patients (70%) who were evaluable achieved MRD after one cycle, with 91% overall achieving MRD negativity.
The three-year continuous remission duration rate was 83% for the entire cohort, while the three-year overall survival (OS) rate was 84%. The three-year OS was 90% in patients without a high-risk baseline feature but was 78% in patients with at least one high-risk feature.
Patients who underwent hematopoietic stem cell transplantation in their first remission had a three-year OS rate of 86%, while it was 88% in those who did not.
In the patients receiving inotuzumab ozogamicin, the estimated one-year continuous remission duration rate was 100%, as was the one-year OS rate.
The treatment was “overall well-tolerated,” with one patient discontinuing blinatumomab due to a related grade 2 adverse event, according to the study’s authors. None of the patients discontinued inotuzumab ozogamicin due to toxicity, and no cases of veno-occlusive disease occurred.
“The addition of [inotuzumab ozogamicin] to hyper-CVAD with sequential blinatumomab is safe and highly effective as frontline treatment of Ph-negative B-cell ALL,” Dr. Short and colleagues concluded. “This study shows the feasibility of incorporating both [inotuzumab ozogamicin] and blinatumomab into the frontline treatment of [patients] with B-cell ALL. Outcomes of the [patients] treated in the [inotuzumab ozogamicin] cohort are particularly promising.”
Short N, Jabbour E, Ravandi F, et al. The addition of inotuzumab ozogamicin to hyper-CVAD plus blinatumomab further improves outcomes in patients with newly diagnosed B-cell acute lymphoblastic leukemia: updated results from a phase II study. Abstract #4043. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.