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EWALL-INO: Inotuzumab ozogamicin promising as first-line therapy for BCP-ALL

Presented By
Prof. Patrice Chevallier, Nantes University Hospital, France
ASH 2021
Phase 2, EWALL-INO
Fractionated inotuzumab ozogamicin plus low-intensity chemotherapy was well tolerated and demonstrated high activity as first-line therapy in older patients with CD22-positive, Philadelphia Chromosome-negative (Ph-neg) B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). This was the main primary result of the prospective, multicentre, phase 2 EWALL-INO trial [1].

“The 2-year overall survival rate of BCP-ALL in older patients is approximately 30%,” according to Prof. Patrice Chevallier (Nantes University Hospital, France). “Since BCP-ALL is the most common ALL in older patients, there is a high need for effective therapies. The high expression rate of CD22 in patients with BCP-ALL (>90%) justifies the investigation of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in this population.” The current phase 2 EWALL-INO trial (NCT03249870) included 90 patients (age ≥55 years) with CD22-positive, Ph-neg BCP-ALL to assess inotuzumab ozogamicin via 2 inductions:

  • Induction 1: 0.8 mg/m2 on day 1 and 0.5 mg/m2 on day 8 and 15.

  • Induction 2: 0.5 mg/m2 on day 1 and 8.

The induction periods were followed by 6 cycles of low-intensity chemotherapy and 18 months of POMP maintenance therapy. The primary endpoint was 1-year overall survival (OS).

The complete response rate was 86.7% after induction 1 and 88.8% after induction 2. In addition, 73% of the patients displayed measurable residual disease (MRD) negativity after induction 2. The 1-year OS rate was 78% (see Figure) and the 1-year relapse-free survival rate was 76%. Patients with KMT2A-rearrangement displayed worse OS and relapse rates than other oncogenetic subgroups.

Figure: 1-year OS rate in EWALL-INO [1]

The safety profile of inotuzumab ozogamicin was favourable. Liver toxicity grade 3-4 was reported in 8.8% of the patients and sinusoidal obstruction syndrome was observed in 3.3% of the patients. In total, 3 deaths occurred during induction therapy, and 29 patients died during the follow-up. The deaths during follow-up were attributable to relapse (n=16) or adverse events (n=13).

In conclusion, a reduced dose regimen of inotuzumab ozogamicin plus low-intensity chemotherapy was tolerable and efficacious in older patients with CD22-positive, Ph-neg BCP-ALL.

  1. Chevallier P, et al. Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study. Abstract 511, ASH 2021 Annual Meeting, 11–14 December.


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