Back Back
Novel Immunotherapies in ALL
Addressing Financial Challenges With Use of New Immunotherapies for Relapsed ALL

Released: May 19, 2016

Expiration: May 18, 2017

Activity Information

Activity

Progress
1
Course Completed
Continue

Authors:  Jonathan Webster, MD, and B. Douglas Smith, MD

Case Report
A 60-year-old woman with Philadelphia chromosome (Ph)–positive pre-B acute lymphoblastic leukemia (ALL) was treated in our office with R-hyperCVAD and dasatinib, achieved a CR, and subsequently underwent allogeneic stem cell transplantation (SCT). Following SCT, she was switched from dasatinib to nilotinib as maintenance therapy due to symptomatic pleural effusions. She subsequently was treated with bosutinib and relapsed with a BCR-ABL E255K mutation. Adverse events and disease progression limited the use of all 3 second-generation TKIs, so we decided to treat her with blinatumomab. Our patient’s disease was Ph-positive pre-B ALL, which did not meet the strict FDA-approved indication. We presented her case to the hospital’s Pharmacy and Therapeutics Committee to ensure that this approach was not only reasonable but had clinical data to support its use, including a recent trial of 45 patients with relapsed/refractory Ph-positive pre-B cell ALL showing a 36% ORR. A request to the patient’s insurance company for coverage approval was initially denied.

What would you do in this case?

Relapsed ALL: Changes Underway
The prognosis of adults with relapsed ALL is poor, with a 5-year OS rate of just 7%. Fewer than 50% of patients achieve a second remission with standard chemotherapy. These poor outcomes have led to a proliferation of trials of immunotherapy approaches in relapsed/refractory ALL, both Ph positive and negative. Blinatumomab is currently approved for the treatment of relapsed/refractory Ph-negative pre-B ALL, whereas CAR T cells and inotuzumab ozogamicin are both likely to gain approval in this setting in the near future. Data suggest these novel immunotherapies are more effective than standard chemotherapy with fewer long-term toxicities. However, the early experience with blinatumomab indicates that the cost of these treatments may be a barrier to their use, particularly when used off label such as in the case example. Therefore, healthcare providers may have to weigh cost with the substantial clinical benefit when planning treatment for some of their patients with ALL.

Blinatumomab
Blinatumomab is a bispecific T-cell engager antibody construct with dual affinity for CD19 and CD3—this brings CD19+ tumor cells near CD3+ cytotoxic T cells that can attack and eliminate them. The trial that led to FDA approval of blinatumomab for the treatment of relapsed/refractory Ph-negative pre-B ALL demonstrated a response rate of 43%. There is general consensus that eligible patients who achieve remission should proceed to allogeneic SCT within the first few cycles of treatment, as the median relapse-free survival among patients achieving remission with blinatumomab was 5.9 months. Those who are ineligible for allogeneic SCT may receive up to 5 cycles of treatment, which is administered as a 28-day continuous infusion. Blinatumomab alone costs on average

-->
Continue

Poll

1.
What would you have done in the management of the patient in this case vignette?
Submit