All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know ALL.

The ALL Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Introducing

Now you can personalise
your ALL Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

The ALL Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the ALL Hub cannot guarantee the accuracy of translated content. The ALL Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
LOADING
You're logged in! Click here any time to manage your account or log out.
LOADING
You're logged in! Click here any time to manage your account or log out.
2023-07-03T10:12:40.000Z

Inotuzumab ozogamicin and blinatumomab in older adults with newly diagnosed B-ALL: ALLIANCE trial

Jul 3, 2023
Share:
Learning objective: After reading this article, learners will be able to cite a new clinical development in ALL.

Older patients (≥60 years) with newly diagnosed Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) have poor survival with conventional chemotherapy. The phase II ALLIANCE A042001 (NCT05303792) trial investigated induction with inotuzumab ozogamicin (InO) and consolidation with blinatumomab in older adult patients with relapse/refractory (R/R) ALL. The study hypothesized that this regimen would improve 1-year event-free survival (EFS) compared with historical outcomes with conventional chemotherapy (1-year EFS, 10%). The aim was to provide an alternative treatment to conventional chemotherapy as first-line therapy in older patients (≥60 years old) who may experience multiagent chemotherapy regimens as toxic and only modestly effective.

Study design

This phase II, interventional clinical trial enrolled patients who were previously untreated for CD22+ Ph-negative ALL. Patients eligible for this study had Ph-negative B-ALL and were

  • ≥60 years of age;
  • had an Eastern Cooperative Oncology Group Performance Status of 0 to 2;
  • had no planned allogeneic or autologous hematopoietic cell transplant (HCT);
  • had no active central nervous system or testicular leukemia or additional malignancy active within the previous 2 years; and
  • had no history of chronic liver disease, veno-occlusive disease/sinusoidal obstruction syndrome, significant cardiac disease, or clinically relevant neurologic disorder.

The study consisted of a treatment schema involving two courses of InO given at an induction dose on a weekly basis before a response assessment. Patients who showed response after the first assessment went on to receive a second dose of InO and those who did not went straight onto consolidation therapy (Figure 1).

The primary endpoint was estimated 1-year EFS (event = progression of disease prior to the end of cycle 2 of consolidation blinatumomab, relapse, or death from any cause). Secondary endpoints included overall survival, relapse-free survival, complete response rate, minimum residual disease (MRD) negativity rate, treatment-related mortality, and safety and tolerability.

Figure 1. Patient treatment schema for ALLIANCE A042001* 

ALL, acute lymphoblastic leukemia; CIV, continuous intravenous infusion; CNS, central nervous system; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; InO, inotuzumab ozogamicin; IT MTX, intrathecal methotrexate; R/R, relapsed/refractory.
*Adapted from Wieduwilt, et al.1

Results

A total of 33 patients aged between 60–84 years were treated. At baseline, 24% had prior malignancy and chemo/radiotherapy and 18% had multiple myeloma. Additionally, 92% had CD22 expression. Baseline characteristics are summarized in Table 1.

Table 1. Baseline characteristics*

Characteristic, % (unless otherwise stated)

Total (N = 33)

Age

 

               Median, years (range)

71 (60-84)

               ≥70 years

52

Race

 

               White

85

               Asian

3

               Not reported / unknown

12

Ethnicity

 

               Not Hispanic or Latino

82

               Hispanic or Latino

9

               Unspecified

9

Gender

 

               Male

58

ECOG performance status

 

               0

24

               1

58

               2

18

Prior malignancy and chemo-RXT

 

               Any

24

               Multiple Myeloma

18

Presenting WBC (range), median ×1000/mcl

3.2 (0.6–38)

Median CD22 expression (range)

92 (21–100)

ECOG, Eastern Cooperative Oncology Group; WBC, white blood count; RXT, radiotherapy.
*Adapted from Wieduwilt, et al.1

 

Hematologic response and efficacy

The study met its primary endpoint and overall survival after one year was promising, with median overall survival not been reached (95% confidence interval [CI], 31 months–not reached) (Figure 2). In total, 12 events were recorded in all patients, with nine patients relapsing from the systemic central nervous system, CD19 or CD22 negative.

Composite complete remission was achieved by 96% of patients in both treatment groups, with 60% of this group achieving complete responses. Complete response/complete remission with partial hematologic recovery/complete remission with incomplete hematologic recovery was achieved by 85% of patients on the course of treatment IA/IB/IC and CR was achieved by 58% of patients by the end of the second course of treatment.

Figure 2. Efficacy outcomes* 

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

Safety

The most common ≥Grade 3 adverse events reported in over 30% of patients were decreased neutrophil count (87.9%), platelet count decrease (72.7%), anemia (42.4%), and white blood cell decrease (39.4%). Overall, there were nine deaths, six due to relapsed ALL and three due to adverse events.

Conclusion

The ALLIANCE A042001 trial reached its primary endpoint. The author concluded that a conventional chemotherapy-free regimen of InO induction and blinatumomab consolidation was highly effective and safe in older patients with newly diagnosed Ph-negative CD22+ B-ALL. Further study is required to establish the significance of these results; however, this trial shows InO plus blinatumomab may be a more suitable alternative to conventional chemotherapy in this population of patients.

In your experience, which treatment goals are most important for older adult patients with acute lymphoblastic leukemia?

Minimal side effects

100%

Disease control

0%

Fewer hospital visits

0%

Maintaining QoL

0%

1 vote

  1. Wieduwilt MJ. Chemotherapy-free treatment with inotuzumab ozogamicin and blinatumomab for older adults with newly diagnosed, Ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia: Alliance A041703. Oral abstract #7006. 2023 American Society of Clinical Oncology Annual Meeting; June 6, 2023; Chicago, US.

Newsletter

Subscribe to get the best content related to ALL delivered to your inbox