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)

Blinatumomab improved overall survival in R/R acute lymphoblastic leukemia (ALL)

This confirmatory study supported the accelerated FDA approval of blinatumomab (BLINCYTO; Amgen) for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Blinatumomab was FDA approved in December 2014 as a breakthrough therapy for Philadelphia chromosome-negative (Ph-) B-cell precursor ALL and was granted conditional marketing approval in the EU in November 2015 for adults with R/R Ph- B-cell precursor ALL.

Overall survival (OS) was prolonged almost 2-fold with blinatumomab vs standard of care (SOC) chemotherapy in R/R ALL (7.7 months vs 4.0 months, respectively). The open-label TOWER phase 3 study randomized patients 2:1 to receive blinatumomab (n=271) or SOC (n=134). Patients had R/R Ph- B-cell precursor ALL. 

The trial was ended early for efficacy based on the recommendation of an independent data monitoring committee. This was the first study to show improved survival with immunotherapy vs SOC in R/R ALL.

"Acute lymphoblastic leukemia is the most aggressive type of B-cell malignancy," said Max S. Topp, MD, professor and head of hematology, University Hospital of Würzburg, Germany. "The data presented today not only reinforce the potential of immunotherapy delivered by T cell engaging bispecific antibody constructs, but also validate the efficacy of BLINCYTO in these heavily pretreated patients."

Blinatumomab is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct. It binds specifically to CD19 on B-precursor ALL cells and to CD3 on normal T cells. This type of modified antibody juxtaposes T cells to cancer cells. 

Currently, no broadly accepted standard regimen exists for adult patients with ALL beyond chemotherapy. The prognosis for adults with R/R ALL is typically very poor, as their median OS is 3 to 5 months.

The OS benefit from blinatumomab vs SOC for intent-to-treat patients (stratified log-rank p=.012; HR=0.71 [95% CI, 0.55-0.93]) held across subgroup analyses. 

When the OS data were censored for allogeneic hematopoietic stem cell transplantation (allo-HSCT), the median OS was 6.9 months for blinatumomab treatment (95% CI, 5.3-8.8 months) vs 3.9 months for SOC (95% CI, 2.8-4.9 months; stratified log-rank p=.004; HR=0.66 [95% CI, 0.50-0.88]). 

Further, blinatumomab improved OS regardless of age, for 0 or 1 prior salvage therapy, for  +/- prior allo-HSCT, and for baseline bone marrow blasts above or below 50%.

Overall response rate was 45% in the blinatumomab group vs 30% in the SOC group (p=.007). Complete remissions occurred in 34% of patients treated with blinatumomab and 16% of patients treated with SOC (p<.001). 

Among patients who responded, molecular remission (<10-4 blasts in the first 12 weeks) occurred in 76% of patients treated with blinatumomab and 48% of patients treated with SOC. 

Adverse events in patients treated with blinatumomab were consistent with prior studies. Blinatumomab was associated with less frequent Grade 3 or higher neutropenia and infection than SOC, while both treatment regimens had similar rates of neurologic events of Grade 3 or higher (9% vs 8%).

Pages: 1 2 3

Post a Comment

OBR Archives

To view previous issues of OBR green you can visit our archives. The entire library of OBR green articles is searchable.