Combination of Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Relapsed or Refractory Ph-Negative ALL

Key Points

  • In patients with relapsed or refractory Ph-negative ALL, response to inotuzumab with low-intensity mini–hyper-CVD chemotherapy was achieved in 78% of patients; median overall survival was 11 months.
  • Veno-occlusive disease occurred in 15% of patients. 

In a single-center phase II trial reported in JAMA Oncology, Jabbour et al found that the combination of inotuzumab ozogamicin (Besponsa) and low-intensity chemotherapy produced promising results in patients with relapsed or refractory Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL).

Study Details

In the study, 59 patients were treated at MD Anderson Cancer Center with inotuzumab ozogamicin and mini–hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine). Compared with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), the lower-intensity mini–hyper-CVD regimen consists of cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine. Inotuzumab ozogamicin was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles, with the lower doses being used after observation of veno-occlusive disease at the initial doses. The primary endpoints were overall response rate and overall survival. Overall, 30 patients were female, and the median age was 35 years (range = 18–87 years).

Efficacy Outcomes

Median follow-up was 24 months. Response was observed in 46 patients (78%), with a complete response occurring in 35 patients (59%). Among responders, 82% were negative for minimal residual disease. Allogeneic stem cell transplantation (ASCT) was received by 26 patients (44%). Median relapse-free and overall survival were 8 and 11 months, with 1-year rates of 40% and 46%. Overall survival at 1 year was 57%, 26%, and 39% (P = .03) for patients receiving salvage 1, salvage 2, and salvage ≥ 3 treatment, respectively.

Adverse Events

Grade 3 or 4 adverse events included prolonged thrombocytopenia in 81% of patients, infection in 73%, and hyperbilirubinemia in 14%. Overall, 95% of patients had hepatic adverse events of any grade, with grade ≥ 3 events occurring in 12 patients (20%). Veno-occlusive disease occurred in nine patients (15%), all of whom had ASCT; of them, three had received ASCT prior to inotuzumab ozogamicin treatment, five received ASCT after inotuzumab ozogamicin, and one had ASCT both before and after treatment.

The investigators concluded: “The combination of inotuzumab with low-intensity mini-[hyper]-CVD chemotherapy shows encouraging results in [relapsed/refractory] ALL. The risk of [veno-occlusive disease] should be considered carefully in patients with previous liver damage and among transplant candidates.”

The study was supported by grants from Pfizer.

Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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