Inotuzumab Ozogamicin Shows MRD Clearance in B-Cell ALL Trial

Inotuzumab ozogamicin (Besponsa) cleared measurable residual disease (MRD) in most adults with B-cell acute lymphoblastic leukemia (ALL) in morphologic remission, according to findings from a single-center phase 2 trial (NCT01371630) published in Blood Cancer Journal.¹

What were the efficacy results with inotuzumab ozogamicin?

The overall MRD negativity rate was 70% (n = 26/37), including 76% (n = 13/17) of patients with Philadelphia chromosome (Ph)–negative ALL and 65% (n = 13/20) of those with Ph-positive ALL. By assessment method, MRD negativity was achieved in 90% (n = 19/21) of patients by multiparameter flow cytometry, 73% (n = 11/15) by next-generation sequencing (NGS), and 59% (n = 10/17) by BCR::ABL1 transcripts.

Responses were rapid, occurring after a median of 1 cycle in patients with Ph-negative disease. With a median follow-up of 50 months, the median overall survival (OS) was 61 months, and the median relapse-free survival (RFS) was 40 months. Outcomes favored patients treated earlier; those treated in first complete remission (CR1) had a median OS that was not reached vs 14 months (95% CI, 9.2-18.5) for patients treated in second or later remission (CR2+; P = .056).

What was the safety profile of inotuzumab ozogamicin?

Inotuzumab ozogamicin was well tolerated, and investigators observed manageable adverse effects (AEs). Three cases (8%) of nonfatal sinusoidal obstruction syndrome (SOS) were observed. All patients received supportive care with ursodiol for SOS prophylaxis throughout treatment.

The safety findings were consistent with the known profile of the antibody-drug conjugate, supporting its use in patients in remission who may subsequently proceed to allogeneic stem cell transplantation or CAR T-cell therapy in a lower-disease state. The most common treatment-related AEs of any grade included thrombocytopenia (70%), increased aspartate aminotransferase (51%), and increased alanine aminotransferase (49%).

“Our results show that inotuzumab is highly effective at clearing residual disease in patients already in remission, with durable responses and encouraging survival,” lead study investigator Elias Jabbour, MD, a professor in the Department of Leukemia and Division of Cancer Medicine at MD Anderson Cancer Center, stated in a press release on these findings.² “This approach has the potential to deepen remissions and change how we manage patients at high risk of relapse.”

What was the trial design?

The phase 2, single-center study enrolled adults 18 years or older with B-cell ALL in morphologic remission and detectable MRD at more than 1 × 10⁻⁴ by multiparameter flow cytometry, BCR::ABL1 transcripts of more than 0.01% by polymerase chain reaction, or more than 1 × 10⁻⁶ by NGS.

Patients received intravenous inotuzumab ozogamicin at 0.6 mg/m² on day 1 and 0.3 mg/m² on day 8 in cycle 1, followed by 0.3 mg/m² on days 1 and 8 in cycles 2 to 6, for up to six 28-day cycles. Patients with Ph-positive disease could receive concurrent tyrosine kinase inhibitors.

Of the 37 patients treated, the median age was 49 years (range, 19-71), 20 had Ph-positive ALL, 17 had Ph-negative ALL, and 76% were in CR1. The primary end point was RFS, with secondary end points including OS, MRD negativity rate, and safety.

What is inotuzumab ozogamicin, and why does clearing MRD matter?

Inotuzumab ozogamicin is an anti-CD22 antibody-drug conjugate linked to calicheamicin that is approved for relapsed or refractory B-cell ALL. MRD is among the strongest predictors of relapse and survival in ALL, and its eradication—particularly in CR1 and by NGS—has been associated with favorable long-term outcomes.

References

1. Jabbour E, Rausch CR, Goulart H, et al. Inotuzumab ozogamicin therapy for measurable residual disease in adult acute lymphoblastic leukemia. Blood Cancer J. Published online June 27, 2026. doi:10.1038/s41408-026-01551-6
2. Novel antibody-drug conjugate eliminates residual cancer cells in majority of patients with B-cell ALL. News release. The University of Texas MD Anderson Cancer Center. July 7, 2026. Accessed July 8, 2026. https://tinyurl.com/y66n9a7h