Optimizing treatment for adults with R/R Ph-negative B-cell ALL

During the ALL Hub Steering Committee meeting, Wendy Stock chaired a discussion on optimizing treatment for adults with relapsed/refractory (R/R) Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL), featuring André Baruchel, Nicolas Boissel, Mark Litzow, José María Ribera, Elias Jabbour, and Sabina Chiaretti.

This discussion was based on a patient case (Figure 1) and focused on four key questions:

• What are the therapy options to induce a remission prior to chimeric antigen receptor (CAR) T-cell therapy?
• What is the optimal use of inotuzumab ozogamicin (InO) to induce a remission and reduce the disease burden (dosing, number of cycles)?
• What should be monitored during therapy, and how can monitoring impact treatment to maximize patient outcomes?
• What are your management strategies following CAR T-cell therapy?

Figure 1. Patient case​

B-ALL, B-cell acute lymphoblastic leukemia; CAR, chimeric antigen receptor; CVAD, cyclophosphamide-vincristine-daunorubicin-dexamethasone; InO, inotuzumab ozogamicin.

Stock presented results from an analysis of the impact of bridging therapy with and without InO in adult patients with R/R B-ALL prior to treatment with obecabtagene autoleucel in the phase Ib/II FELIX trial (NCT04404660). Bridging therapies containing InO effectively reduced disease burden and, although the patients in the InO group had a higher baseline bone marrow blast percentage (bridging with InO, 73%; bridging without InO, 34%; no bridging therapy, 20%), efficacy outcomes were better in those that received bridging with vs without InO (Table 1).¹

Table 1. Efficacy outcomes following obe-cel infusion following bridging therapy with and without InO in the FELIX trial*

Stock then highlighted the key considerations for the use of InO in patients with R/R B-ALL, including advantages and limitations, potential dose modifications when used as a bridging therapy, toxicities associated with InO, and the impact of measurable residual disease (MRD) on outcomes. Finally, Stock discussed alternative bridging strategies, and potential complications following CAR T-cell therapy.

Discussion

Key discussion points included:

• The goal of bridging therapy is cytoreduction with minimal toxicity, and achieving a complete remission may not be necessary.
  • One cycle of InO with standard dosing (0.8 mg/m² on Day 1 and 0.5 mg/m² on Days 8 and 15) prior to CAR T-cell therapy may be sufficient, and MRD monitoring can help guide treatment decisions.
• Treatment with InO can result in rapid responses irrespective of baseline disease burden; however, as with all treatments, disease biology can affect the efficacy.
• B-cell aplasia and MRD should be monitored often to assess treatment response, and monitoring strategies can change depending on the genetics of the disease and the type of CAR T-cell therapy used.
• The management of CAR T-cell therapy complications is improving, and earlier intervention may improve outcomes.
• The panel discussed whether patients should proceed to transplantation following CAR T-cell therapy, and the factors impacting this decision.
  • There is a need to evaluate whether targeted immunotherapy bridging alone may suffice to proceed directly to transplantation.

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