CAR-T therapies have shown impressive results in acute lymphoblastic leukemia. But so far, no cell therapy has been approved to treat chronic lymphocytic leukemia, a more prevalent form of blood cancer. And Bristol Myers Squibb wants to change that with Breyanzi.
A phase 1/2, single-arm trial testing Breyanzi in previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) has hit its goal, Bristol Myers said Thursday. The CD19-targeted CAR-T met the goal when compared with historical control in clearing signs of tumor, namely, triggering complete responses.
BMS said it will complete a full evaluation of the current TRANSCEND CLL 004 trial data and will discuss them with health authorities.
CLL represents a large indication. AbbVie and Johnson & Johnson’s BTK inhibitor Imbruvica, thanks mainly to its frontline CLL nod, registered more than $8 billion in sales in 2022. And as BMS noted, there’s currently no standard of care for relapsed or refractory CLL/SLL after prior treatment with targeted agents.
The question is: Are the Breyanzi data enough to support an FDA application? And if approved, will they make a difference in CLL treatment?
Right now, without specifics, it remains unclear.
In this study, Breyanzi met its complete response goal in heavily pretreated CLL/SLL patients whose cancer was refractory to a BTK inhibitor such as AbbVie and Johnson & Johnson’s Imbruvica and had failed on AbbVie and Roche’s BCL-2 inhibitor Venclexta.
Historically, positive complete response rates in heavily pretreated blood cancer patients have been enough to begin an FDA review.
The TRANSCEND CLL 004 trial marks the first multi-center trial evaluating a CAR-T cell therapy in heavily pretreated CLL/SLL, BMS’ head of cell therapy development, Anne Kerber, said in a statement Thursday. BMS’ rival, Gilead Sciences’ Kite Pharma, currently doesn’t list a CLL trial for its CAR-T pipeline. And there’s a reason for the lack of progress. As Kerber noted, CLL’s complex biology and immune dysregulation have made the development of T cell therapies “very challenging.”
Past early-stage trials of CAR-T therapy in CLL showed an average complete response rate of around 30%, a study published last year in the journal Current Oncology found. That was less exciting than the near-70% complete response rates that CD19 CAR-Ts have shown in ALL.
But when CAR-Ts do elicit a complete response, the effect could be long-lasting, potentially amounting to a cure. In a landmark Nature study published last year, a team led by cell therapy pioneer Carl June found that two patients with end-stage CLL were still in remission about 10 years after treatment with Novartis’ CD19 CAR-T Kymriah.
By comparison, Lilly’s small-molecule pirtobrutinib didn’t trigger a single complete response in a post-BTK-BCL2 subgroup in its own phase 1/2 BRUIN trial.
Still, because CLL patients are typically older and have undergone significant treatment, their immune systems may be impaired, making them less-than-ideal candidates for CAR-T treatment.