- Updated results from a pivotal study of Gilead Sciences Inc.'s CAR-T therapy Yescarta offers new proof of the treatment’s benefit over the longer term, suggesting those patients who go into remission are likely to remain so more than one year after infusion with the cell therapy.
- In the ZUMA-1 study, 42% of patients with diffuse large B-cell lymphoma (DLBCL) remained in response —and 40% in a complete response — at a median follow-up of 15.4 months, data presented Sunday at the annual meeting of the American Society of Hematology shows.
- "Long-term follow-up of ZUMA-1 confirms that these responses can be durable and the ongoing responses at 24 months suggest that late relapses are uncommon," said Sattva Neelapu, lead study author and professor at The University of Texas MD Anderson Cancer Center, in a statement.
The new data from the ZUMA-1 study is another milestone reinforcing the promising clinical profile of Yescarta (axicabtagene ciloleucel) and, more broadly, CD19-targeted CAR-T therapies.
As Gilead's Yescarta began to gather real momentum last fall and into this past spring, one of the key questions was whether the sparkling initial response rates would be durable. While the numbers for overall and complete response rates fell at the three-month mark, both appeared to stabilize at six months.
With over a year of follow-up data now in hand, the complete response rate remains compelling at 40%. That’s significantly higher than the 7% rate seen in a retrospective study sponsored by Kite Pharma (now owned by Gilead) of patient outcomes with other available therapies.
Notably, nearly 60% of the 108 patients treated across the Phase 1 and 2 portions of the study remained alive at 12 months.
Twenty three out of 60 patients who had either a partial response or stable disease at one month eventually achieved a complete response as late as 15 months post-infusion without additional therapy.
On the safety side, no late-onset cases of cytokine release syndrome or neurotoxicity, two known side effects of CAR-T treatments, were observed. Eight new infections, however, did occur after six months of follow-up.
Long-term data like this won't factor into Yescarta's existing approval for relapsed and refractory DLBCL patients. But it does help bolster Gilead's case that, for some, CAR-T can function as the one-time treatment it is envisioned to be. That will be important in winning over payers, as Yescarta currently carries a list price of $373,000.
For those who still relapse following CAR-T treatment, the updated analysis presented at ASH gives some clues as to why.
In a third of patients who relapsed post-infusion, tumor cells stopped expressing the CD19 antigen that Yescarta is engineered to target. Loss of CD19 could thereby render the CAR-T cells less effective, the thinking goes. Other tumors analyzed showed signs of a protein called PD-L1 that can act as an immunosuppressant.
These findings are important because they suggest directions for improving CAR-T and broadening the number of patients who can benefit. Pairing CAR-T with a checkpoint inhibitor that targets PD-L1 could be one option, for example. Designing a CAR-T to lock onto two different antigens to overcome loss of CD19 could be another way.
Gilead has already taken a step in this direction with its recent acquisition of Cell Design Labs, which specializes in engineering cells like CAR-Ts.