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Phase II trial results of inotuzumab ozogamicin in older patients with de novo B-ALL: GMALL-INITIAL1 trial

Jan 19, 2023
Learning objective: After reading this article, learners will be able to cite a new clinical development in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) represents 5% of all newly diagnosed leukemias in older patients aged 55–70 years. With recent advances mainly being focused on younger populations, older patients have seen limited prognostic benefit. Survival outcomes for elderly patients remain poor with age-adapted, dose-reduced chemotherapy regimens, even after moderately intensive doses; this patient subset is ineligible for unmodified pediatric-based therapies.1

The ALL Hub has previously reported on the efficacy and safety of inotuzumab ozogamicin (InO) as a frontline treatment for older patients (>55 years) with Philadelphia-chromosome-negative (Ph) ALL.1 InO plus mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone has demonstrated promising survival rates in older patients with Ph ALL.1,2

Below, we summarize recent efficacy and safety data from the phase II GMALL-INITIAL-1 trial (NCT03460522) investigating InO induction in patients with de novo Ph ALL, presented by Stelljes at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in 2022.2

Study design

This study was conducted across 13 sites in Germany and included patients enrolled between June 2018 and April 2021. Eligible patients were aged >55 years, had CD22+ Ph B-ALL with or without CNS involvement, and had received no previous ALL-specific treatment (except prephase). The treatment schedule consisted of three cycles of InO induction, conventional chemotherapy consolidation, and subsequent maintenance (Figure 1). 

Figure 1. Study design*

ARAC, cytarabine; Asp, asparaginase; 6MP, 6-mercaptopurine; MTX, methotrexate.
Administered intrathecally.
*Adapted from Stelljes, et al.2

The primary endpoint was event-free survival at the 12-month follow-up. An event was defined as any of the following: persisting bone marrow blasts after two cycles of InO, relapse, or death. An event rate of <40% at 12 months was considered promising for further evaluation.

Secondary endpoints included remission rates, rate of minimal residual disease negativity, remission after induction treatment, relapse-free survival and overall survival at two 2-years, rate of deaths during induction/and or death in complete remission (CR), and the proportion of patients with molecular relapse.


Updated efficacy2

Of the 45 patients included, 43 were evaluable for hematological remission and follow-up assessments. Baseline characteristics are summarized in Table 1.

Table 1. Baseline characteristics*

Characteristic, n (unless otherwise stated)

n = 43

Median age (range), years

64 (56–80)

               >65 years


               >70 years








Common ALL features


Pro B-ALL features


Blasts >20% positive for CD20


Median CD22 expression (range)

69 (21–99)

               Blasts >20-40% positive for CD22


               Blasts >40-60% positive for CD22


               Blasts >60% positive for CD22


B-ALL, B-cell acute lymphoblastic leukemia.
*Adapted from Stelljes et al.2

Overall, induction with InO resulted in high remission rates (Table 2).

Table 2. Response rates*

Hematological remission, % (unless otherwise stated)

n = 43

CR/CRi after 2 induction cycles


Patients receiving three cycles of InO


Early deaths within the first 6 months


Evaluable for MRD

MRD negative after 2nd induction cycle


MRD negative after 3rd induction cycle


Median time between 1st and 2nd induction (range), days

21 (21–31)

Median time between 2nd and 3rd induction (range), days

28 (27–33)

Median time and between 3rd induction  1st consolidation (range), days

30 (26–42)

CR, complete remission; CRi, complete remission with incomplete count recovery; InO, inotuzumab ozogamicin; MRD, minimal residual disease.
*Adapted from Stelljes, et al.2
One patient received only two induction cycles (died in molecular CR).
n = 31/42

  • Within the first year, a total of five events occurred; two patients with relapsed disease and three deaths in CR
  • The primary endpoint was met, with an event rate of 12%
  • At a median follow-up of 697 days, the study showed promising overall survival and event-free survival rates at 1 and 2 years (Figure 2)

Figure 2. 1 and 2-year OS and EFS* 

EFS, event free survival; OS, overall survival.
*Adapted from Stelljes, et al.1

As of July 2022, subsequent treatment given includes blinatumomab in seven patients (five for relapse and two for minimal residual disease), InO in three patients (for relapse), CAR-T-cell therapy in one patient (for relapse), and allogeneic hematopoietic cell transplantation in ten patients (six after relapse and four in 1st CR).

Updated safety2

Adverse events mostly occurred in the first induction cycle of InO and were likely to be disease related. The three most common adverse events overall were leukocytopenia, anemia, and thrombocytopenia (Table 3).

Table 3. Grade 3–4 AEs reported after INO induction*

CTC AEs > 5% (3-4; 4.0)

Induction 1
(n = 43)

Induction 2
(n = 43)

Induction 3
(n = 42)

















Elevation of GOT/GPT





Elevation of bilirubin










Febrile neutropenia










AE, adverse event; CTC, Common Terminology Criteria; GOT; glutamic oxalacetic transaminase; GPT; glutamic pyruvic transaminase; INO, inotuzumab ozogamicin; VOD, veno-occlusive disease.
*Adapted from Stelljes, et al.1

One patient reported with suspected VOD after 2nd induction cycle.


In this study, InO as induction therapy demonstrated high efficacy and a manageable toxicity profile in older patients with B-ALL. The study reported high remission rates, promising survival outcomes and no early deaths in the first 6 months. These results provide a basis for the integration of InO induction in future treatment recommendations; however, evaluation in prospective randomized trials is needed.

  1. Stelljes M. Final induction therapy results of an open label phase II study using inotuzumab ozogamicin for induction therapy, followed by a conventional chemotherapy based consolidation and maintenance therapy in patients aged 56 years and older with acute B-lymphoblastic leukemia (INITIAL-1 trial). Poster #2300. 63rd American Society of Hematology Annual Meeting and Exposition; Dec 12, 2021; Atlanta, US.
  2. Stelljes M. Inotuzumab ozogamicin induction followed by standard chemotherapy yields high remission rates and promising survival in older (>55 Years) patients with de novo B-lymphoblastic leukemia (GMALL-Initial1 Trial). Oral abstract #212. 64th American Society of Hematology Annual Meeting and Exposition; Dec 10, 2022; New Orleans, US.