September 2016 Edition Vol.11, Issue 9

EHA 2016: Stopping TKIs in CML and Improving Overall Survival in ALL

EHA 2016: Stopping TKIs in CML and Improving Overall Survival in ALL (continued)

Inotuzumab Ozogamicin in R/R ALL

In the phase 3 INO-VATE study of relapsed or refractory ALL (n=326), 2-year survival rates increased to 23% with inotuzumab ozogamicin (Pfizer) compared with 10% with SOC. The FDA granted breakthrough therapy designation for inotuzumab ozogamicin in October 2015. This designation was based on an interim analysis from the INO-VATE trial, and the final results of that trial were presented at EHA 2016. 

“Relapsed or refractory ALL is an aggressive leukemia in urgent need of new treatment options as about half of adult patients will not respond to chemotherapy or will see their disease return,” said Hagop M. Kantarjian, MD, lead study investigator and professor, The University of Texas MD Anderson Cancer Center, Houston, Texas. 

Only 20% to 40% of newly diagnosed adults with ALL are cured with current treatment regimens. Further, for adults with ALL who relapse after first-line therapy or are refractory to it, only 10% will survive 5 years or more with current treatment options.

Inotuzumab ozogamicin is an antibody-drug conjugate that targets CD22, which is found on cancer cells in almost every B-ALL patient. The antibody is linked to a cytotoxic agent, calicheamicin, which induces apoptosis.

“The efficacy results seen in patients treated with inotuzumab ozogamicin in this study are impressive, particularly median progression-free survival, high rates of hematological remission, and absence of minimal residual disease,” stated Kantarjian. 

Patients treated with inotuzumab ozogamicin had a median progression-free survival of 5.0 months vs 1.8 months with SOC (hazard ratio=0.45; p<.001). 

Complete responses were 80.7% with inotuzumab ozogamicin vs 29.4% with SOC. Minimal residual disease (MRD) was negative for 78.4% of the patients treated with inotuzumab ozogamicin vs 28.1% of patients treated with chemotherapy.

“About 3 to 5 times more patients on inotuzumab were ultimately able to access allogeneic stem cell transplantation. In my opinion, inotuzumab is well tolerated with appropriate prevention measures,” said Kantarjian. “These results suggest inotuzumab ozogamicin, if approved, could be a valuable new addition to currently available treatment options for ALL patients, including as a bridge to stem cell transplantation, which is the best chance for a cure at this stage of the disease.”

Inotuzumab ozogamicin treatment allowed 41% of patients to proceed to stem-cell transplant vs 11% of patients treated with SOC (p<.001).2

Cytopenias were the most common treatment-emergent adverse events in both arms. Inotuzumab led to a higher incidence of liver function abnormalities (all Grade, 23% vs 11%). 

Veno-occlusive liver disease (VOD) was more common in the inotuzumab arm than in the SOC arm (11% vs 1%, respectively), though only 3% of the patients receiving inotuzumab developed VOD prior to SCT.

“My hope is that in the near future, inotuzumab will be used not as a single agent, but in combination with chemotherapy or with other monoclonal antibodies that target CD19 both in salvage and frontline settings. This will hopefully improve the outcome of patients with ALL significantly compared to what we know today,” concluded Kantarjian.

References

  1. Sweet K and Oehler V. Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when is this a safe option to consider? Hematology Am Soc Hematol Educ Program. 2013;2013:184-188. doi: 10.1182/asheducation-2013.1.184.
  2. Kantarjian HM et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. New Engl J Med. 2016;375(8):740-753.

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