- A CAR-T cell therapy acquired by Celgene earlier this year could have a path forward in chronic lymphocytic leukemia (CLL), showing initial signs of efficacy in a small group of heavily pretreated patients with the blood cancer.
- Treatment with JCAR017, the main asset picked up in the biotech's $9 billion buyout of Juno, led to a response in 13 out of 16 patients with relapsed refractory CLL or small lymphocytic leukemia (SLL) who had been previously treated with Imbruvica. Seven of those responders went into a complete response.
- To date, CAR-T therapies have proven effective in acute lymphoblastic leukemia and in B-cell lymphoma. Celgene's not alone in exploring CLL, though. Gilead plans to begin a Phase 1 study of its CAR-T therapy later this year, while Novartis' Kymriah has been studied in the slower-growing cancer type at the University of Pennsylvania.
To a large degree, Celgene bought Juno for JCAR017, a CD19-targeted CAR-T therapy that the big biotech hopes will enable it to catch rivals Gilead and Novartis.
But the timeline for JCAR017's date with regulators in its lead indication of B-cell lymphoma has slipped, raising questions about Celgene's competitive positioning.
Just last December, for example, then independent Juno predicted JCAR017 would be approved as "early as the end of 2018." Celgene walked that back upon acquisition and now forecasts an approval in lymphoma by mid-2020.
Promised a pipeline in a drug, investors may take some solace that the therapy looks to have potential in CLL, too.
The fresh study results were unveiled Sunday at the annual meeting of the American Society of Hematology in San Diego. Notably, data were updated from a study abstract released ahead of the meeting, showing a higher response rate in a greater number of patients.
All 16 patients included in this latest data cut were previously treated with AbbVie and J&J's Imbruvica (ibrutinib), now a standard and highly effective therapy in CLL. Roughly 80% of those patients were refractory or resistant to Imbruvica.
Follow-up, though, is short. In CAR-T therapy, a key test of efficacy is how long responses endure. On that front, all five patients with six months or more of follow-up remained in response and were negative for minimal residual disease.
Treatment with JCAR017 led to cytokine release syndrome in three quarters of patients, although only one was ruled Grade 3. Three patients experienced Grade 3 neurologic side effects, another key risk to CAR-T cell therapy.
While JCAR017 could represent a potential option for patients who have failed other standard treatments, its potential in CLL may be limited by the strong efficacy of Imbruvica in earlier lines of treatment. Data presented at ASH have further bolstered Imbruvica's profile in both CLL and SLL.
Another possible approach could be combining JCAR017 with Imbruvica. A retrospective analysis also presented at ASH found concurrent administration of Imbruvica and another Juno CAR-T therapy was associated with deep responses and high in vivo expansion of CAR-T cells in patients with relapsed/refractory CLL.