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ATLANTA -- An antibody-drug conjugate (ADC) targeting CD22 achieved a high response rate and exceeded a prespecified survival goal in older patients with newly diagnosed acute lymphoblastic leukemia (ALL), according to a prospective study presented here.

After two cycles of inotuzumab ozogamicin (Besponsa) and low-dose chemotherapy, 88.8% of patients achieved a complete response (CR), and 73% of patients were minimal residual disease (MRD) negative. The 90 patients included in the analysis had a 1-year overall survival (OS) rate of 78%, exceeding the 1-year goal of 70%, or 10% greater than observed in a historical control group.

The regimen was generally well tolerated, reported Patrice Chevallier, MD, PhD, of Nantes University Hospital in France, during the American Society of Hematology annual meeting.

"The combination of fractionated inotuzumab with low-dose chemotherapy is a very active and well-tolerated frontline therapy for older patients with CD22-positive, Philadelphia chromosome [Ph]-negative B-cell precursor-ALL," he concluded. "After induction, the median survival was not reached, but 1-year survival was almost 80%. Liver toxicity was very low, only 3% SOS [sinusoidal obstruction syndrome]. Few patients received allo-transplantation. As inclusions continue to a total of 130 patients, we will look at the impact of prognostic factors, including MRD."

B-cell precursor (BCP)-ALL accounts for a majority of ALL in older patients. The condition represents a large unmet clinical need, associated with a 2-year OS rate of about 30%, Chevallier noted.

CD22 expression is almost universal in BCP-ALL. Inotuzumab ozogamicin consists of an anti-CD22 antibody conjugated to the cytotoxic agent calicheamicin. The agent has FDA approval for relapsed/refractory CD22-positive BCP-ALL in adults. In a previous , inotuzumab plus low-intensity chemotherapy led to a 2-year OS rate of 66% and a progression-free survival (PFS) rate of 59% in a group of older patients with newly diagnosed Ph-negative BCP-ALL.

Chevallier and colleagues sought to build on the earlier results with fractionated inotuzumab plus low-intensity chemotherapy. Patients received three doses of inotuzumab during a first induction, and those who achieved a CR (including CR with platelets <100 G/L; CRp) received a second induction that included two doses of inotuzumab. The induction regimen did not include an anthracycline, cytarabine, or rituximab (Rituxan).

Patients who completed both cycles of induction therapy received six cycles of consolidation therapy with cytarabine, methotrexate, and cyclophosphamide. At investigator discretion, patients could undergo allogeneic stem cell transplantation after completing at least three cycles of consolidation therapy. Following consolidation, the patients received 18 months of maintenance therapy.

The trial had a primary endpoint of 1-year OS, and secondary endpoints included CR, death during induction, molecular response, leukemia-free survival, and relapse. Investigators hypothesized that induction with fractionated inotuzumab and low-intensity chemotherapy would improve 1-year OS from 60%, derived from historical control data with , to 70%.

Eligible patients were at least 55 years old, had untreated CD22-positive BCP-ALL, Ph-negative disease, and no central nervous system involvement.

Chevallier reported findings for the first 90 patients, who had a median age of 69 (age range 55-84). The data showed that 73 (81.1%) patients received the planned five doses of inotuzumab, and six patients underwent allogeneic transplantation.

After the first induction, 78 of 90 (86.7%) patients had a CR, including six with CRp, increasing slightly to 80 of 90 (88.8%) after the second induction (eight CRp). Chevallier reported that 49 of the 80 (73%) patients with CR achieved MRD-negative status after the second induction. In addition to a 1-year OS rate of 78%, the study population had a 1-year relapse-free survival rate of 76%.

The safety profile included eight cases of grade 3/4 liver toxicity. Three patients developed SOS, two during induction and one following allo-transplant. Three patients died during induction therapy, and 29 patients died during follow-up. Chevallier said 16 deaths during follow-up were associated with relapse, and 13 with adverse events, including one death associated with COVID-19.

In response to a question from the audience, Chevallier said investigators have not yet studied potential associations between level of CD22 expression and outcomes.

The findings are comparable to those of a of inotuzumab plus mini-hyper-CVD chemotherapy, noted Armin Ghobadi, MD, of Washington University in St. Louis. Mini-hyper-CVD offers the advantage of better tolerability as compared with other chemotherapy regimens.

"Elderly patients with Ph-negative B ALL don't have a standard widely accepted first-line therapy," Ghobadi told 木瓜直播 in an email. "Low-dose chemotherapy with inotuzumab has provided an effective treatment with an acceptable toxicity."

While there is no head-to-head comparison, the "ease of scheduling of mini-hyper CVD plus inotuzumab make it a more attractive option for this group of patients," he said.

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