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NEW ORLEANS -- Consolidation chemotherapy with blinatumomab (Blincyto) improved overall survival (OS) in patients with newly diagnosed measurable residual disease (MRD)-negative B-lineage acute lymphoblastic leukemia (ALL), results from a phase III trial showed.

Median OS was not reached among patients treated with the bispecific CD19-directed CD3 T-cell engager combined with chemotherapy versus 71.4 months for patients treated with chemotherapy alone (HR 0.42, 95% CI 0.24-0.75, P=0.003), reported Mark Litzow, MD, of the Mayo Clinic in Rochester, Minnesota.

Relapse-free survival was not reached in the blinatumomab arm compared with 22.4 months in the chemotherapy-alone arm (HR 0.46, 95% CI 0.27-0.78, P=0.004).

In a planned interim analysis at a median of 43 months, the OS rate was 83% in the blinatumomab arm compared with 65% in the chemotherapy-alone arm.

"This represents a new standard of care for these patients, and should be incorporated into their standard therapy," Litzow said during a press briefing at the 2022 American Society of Hematology annual meeting.

Blinatumomab is already approved by the FDA and in multiple countries for the treatment of relapsed and refractory ALL, as well as in patients with MRD-positive ALL, Litzow noted. "Here, we aimed to test it in patients who were MRD-negative because we know that even if we can't find leukemia in these patients' bone marrow, it's still hiding there, and they can often relapse during their treatment."

Press briefing moderator Cynthia Dunbar, MD, of the National Heart, Lung, and Blood Institute at the NIH, asked how the results of this trial will factor into decisions on whether to send a patient on to allogeneic transplant, "because in adults with B-cell ALL, that is very often thought to be the only route to cure."

Litzow responded that several factors play a role in this decision, including MRD status, with patients who achieve MRD negativity having a better prognosis than patients who are MRD positive.

Additionally, molecular findings indicate "whether [a patient] has a more stubborn leukemia that may come back more frequently," he added. "So, those are some of the factors that weigh into whether we should consider transplant for a patient or not. I think these results suggest that fewer patients will need a transplant, given that with this survival curve it's pretty hard to beat that with a transplant. So, I think we will see diminishing use of transplant in this setting because of these results."

The trial included 488 adults at 77 sites across the U.S., Canada, and Israel. These patients underwent standard induction chemotherapy for about 2 months to induce remission, followed by a 1-month course of intensified chemotherapy designed to prevent the leukemia from reaching the central nervous system.

After evaluation of MRD status (with MRD negativity defined as <0.01%), 224 were found to be MRD-negative and were assigned 1:1 to either the blinatumomab/chemotherapy arm or the chemotherapy-alone arm.

Litzow was asked to explain the large difference between the patients enrolled in the study and those who were eventually randomized. He pointed out that over 100 patients were unable to continue on the study because they did not achieve complete remission, and that a number of patients relapsed quickly after achieving remission.

"So, it certainly raises the question, should we be moving up immunotherapy earlier in the course," Litzow said. "This study was designed over 12 years ago and we've learned a lot since then, and I think that's one of the lessons that comes out of this study as well."

Among the 224 MRD-negative patients, 22 in each arm underwent allogeneic transplant. About 60% received all four cycles of blinatumomab, while 80% received two or more cycles.

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