SAN FRANCISCO—Combining inotuzumab ozogamicin with low-intensity chemotherapy achieved results better than that observed with chemotherapy alone in patients with newly diagnosed B-cell acute lymphoblastic leukemia (ALL), results of a study (Abstract 794) reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
This approach, dubbed miniHCVD-INO, “may become the new standard of care for frontline treatment of older patients with ALL,” said Elias Jabbour, MD, of the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX.
Inotuzumab ozogamicin is a CD22 monoclonal antibody bound to a toxin, calicheamicin; CD22 expression occurs in more than 90% of patients with ALL.
By adding this agent to mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 83% dose reduction), the investigators sought to determine whether outcomes might be improved in this population, which has a significantly worse outcome because they tolerate intensive chemotherapy poorly.
Twenty-eight patients 60 years of age or older received rituximab and intrathecal chemotherapy on days 2 and 8 for the first 4 courses. Inotuzumab ozogamicin was given on day 3 of each of the first 4 courses. The first 6 patients received 1.3 mg/m2 for cycle 1 followed by 0.8 mg/m2 for subsequent cycles; the patients who followed received 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles.
All patients received maintenance therapy with POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) for 3 years.
Median age of the patients was 68 years (range 60-79); 16 patients were men.
Following treatment, 27 patients responded, 22 complete responses and 5 with CR except for platelets (CR/CRp), for an overall response rate of 96%. One patient was enrolled with a CR after dexamethasone and 1 dose of vincristine. All patients who achieved CR also achieved flow-cytometric MRD negative status.
At a median follow-up of 15 months (range, 4-31), 17 patients were alive on POMP maintenance; 2 had relapsed and died; 3 had received consolidation therapy; 1, an allogeneic stem cell transplant; and 4 patients had died, 1 in CR/CRp, 2 from sepsis, 1 of a gunshot wound, and 1 of an unknown cause of death. The 1 patient resistant to treatment died of progressive disease.
The 1-year progression-free survival (PFS) and overall survival (OS) rates were 88% and 81%, respectively; the median was not reached for either PFS or OS.
Grade 3 or 4 adverse events included infections (during induction and consolidation), hemorrhage, cardiac, hyperglycemia, hypokalemia, hyperbilirubinemia, ALT/AST, and hyponatremia.
“Early results are better than those achieved with the HCVAD regimen,” Dr. Jabbour concluded.