Last week saw the release of two studies with new long-term follow-up data on chimeric antigen receptor (CAR) T-cell therapies in B-cell acute lymphoblastic leukemia (ALL). As many expected, the results were positive and provided further evidence that CAR T-cells are a safe and durable treatment option in both pediatric and adult ALL patient populations. The first study gave us more data from Novartis’ ELIANA study in ALL patients up to 25 years old, while the second introduced new data from Memorial Sloan Kettering Cancer Center (MSKCC) for their own CAR T-cell construct, 28-19z, in adult ALL patients (18 years and older).

Kymriah’s FDA approval last year for the treatment of relapsed/refractory ALL in pediatric and young adult patients was heralded as a landmark breakthrough for cancer therapy. The high response rates achieved were unprecedented for the indication, but most experts were cautious about its durability. Though updated results from the ELIANA study will likely put some of those concerns to rest. The current data indicate that Kymriah’s overall remission rate at 3 months was 81% (in 75 patients), little changed from the previously reported 83% (1,2). But importantly, Kymriah was detectable in patients up to 20 months post-infusion, indicating long-term persistence of the one-time treatment. The median follow-up time was 13.1 months, and the median duration of remission is yet to be reached.

As for MSKCC’s surprising new contender in the ALL CAR T-cell space; 28-19z, has longer follow-up data available with a median of 29 months. Their Phase I study reported an 83% complete rate post infusion (53 patients), and resulted in a median overall survival of 12.9 months (3). Most notably patients with low tumor burden had a median overall survival of 20.1 months, significantly higher than for patients with high tumor burden.

For most spectators, these studies will reinforce the role of CAR T-cells in the ALL treatment algorithm, and serve to shift the focus of the CAR T-cell conversation. Indeed, if efficacy and safety are no longer in question, for ALL at least, which are the issues that still need addressing?

Following the real-world rollout of Kymriah for pediatric and young adult ALL, as well as Gilead/Kite’s Yescarta for adult relapsed large B-cell lymphoma, key opinion leaders comment that access and reimbursement are a major bottleneck to treatment. The restriction of CAR T-cell availability to approved treatment centers results in logistical and administrative barriers to access, and uncertain insurance cover continues to limit uptake in the US. While the long-term efficacy and safety concerns of CAR T-cells are yet to be fully resolved, the current evidence appears to be in its favour and support clinical uptake. As patients are keen to gain access to CAR T-cell therapies, these commercialization issues need to be resolved before their true market potential can be realised.


  1. Maude SL et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018; 378:449-459.
  2. Buechner J et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL): Update to the interim analysis. EHA Learning Center. 2017; abstract #S476.
  3. Park JH et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med 2018; 378:449-459.


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