With Hands Tied, CMS' NTAP for Blinatumomab Is Ridden With Controversy

In their Viewpoint in JAMA Oncology, Sanket S. Dhruva, MD, and Vinay Prasad, MD, MPH, have raised objections to CMS’ turnaround on their prior decision with the antibody blinatumomab (Blincyto) in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

Blinatumomab was approved in December 2014 for the treatment of patients with a rare form of acute lymphoblastic leukemia, Philadelphia chromosome-negative precursor B-cell ALL. Blinatumomab is in a new class of molecular constructs called bi-specific T-cell engagers (BiTE). This BiTE antibody represents an innovative immunotherapy approach for fighting cancer by helping the body's immune system to detect and target cancer cells. BiTE constructs can selectively attach to a molecule on the tumor cell surface and to a molecule on the surface of normal T cells. By attaching to both the tumor and the T cell and bringing the 2 into close proximity, the T cells are able to fight the tumor cell. Blinatumomab targets CD19-expressing cells found in leukemias and lymphomas. Directing T cells to these CD19-expressing tumor cells helps the T cells engage with, and destroy, the tumor cells.

Following the FDA approval, Medicare had initially refused to cover the medication estimated to cost $178,000 for a standard course of treatment, which includes 2 continuous 4-week intravenous infusions, separated by a drug-free interval. With severe toxicities such as tumor lysis syndrome, neurologic effects, febrile neutropenia, and cytokine release syndrome, observed in participants in the registration trial, the FDA label recommends hospitalization for the first 9 days for adequate patient monitoring. Considering that only 13% of trial participants were older than 65 years of age—and 84% of Medicare beneficiaries are older than 65 years—CMS initially cited a dearth of information in the Medicare population with this drug.

But the drug developer, Amgen, was persistent, and provided CMS with supplemental evidence that turned the tide, and the government agreed that blinatumomab presented a substantial improvement over existing treatments for some patients. This formed the basis of the antibody being approved for an additional payment under CMS’ new technology add-on payment (NTAP) program.

The point being raised by Dhruva and Prasad in their opinion piece is that is this technology really worth its price to Medicare? The phase 2 study, with its small number of older enrollees, saw less than 42% patients achieve the primary surrogate end point—complete remission with or without partial hematologic recovery. Further, with a median period of just 5.7 months before patients relapsed or died of the disease, blinatumomab probably only helps tide the patients over to receive a stem-cell transplant (SCT) (40% of trial participants did). This complicates matters in Medicare patients who may suffer from comorbid conditions, are not the best candidates for SCTs, and may not be able to withstand the intense toxicity of the drug. Additionally, since the trial was uncontrolled, there is no evidence of improved performance of blinatumomab over the standard of care.

The authors write, “”For these reasons, the initial conclusion of the CMS on the drug’s merits alone was appropriate; no role exists for an NTAP for blinatumomab.” In the absence of cost considerations—since CMS is prevented from including cost in its coverage decisions—CMS is in no position to reject drugs that provide marginal benefits, they write. But with the NTAP program, cost is a consideration because NTAP is not evoked unless a technology is costly, they explain. “NTAP for blinatumomab should be questioned,” they conclude.