It’s possible to compare apples and oranges – both are fruits, after all; likewise, in the absence of head-to-head trials, it’s possible to make an indirect comparison of two immunotherapy strategies for treating relapsed or refractory pediatric acute lymphoblastic leukemia (r/r ALL): chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel (Kymriah), and immunotherapy with the bi-specific T-cell engager (BiTE) blinatumomab (Blincyto).
Michael Verneris, MD, of the University of Colorado Anschutz Medical Center in Aurora, and associates carried out the first such indirect, patient-level comparison of these two immunotherapies.
“The large differences in CR and OS outcomes across multiple differing assessments suggest that our findings describe a true treatment impact. Although the current analysis is retrospective and limited by cross-study comparison, these findings support the growing body of clinical trial and real-world evidence demonstrating that tisagenlecleucel is an important treatment option for children and young adults with r/r ALL,” they wrote in an article published in Blood Advances.
However, as two pediatric leukemia experts uninvolved in the study noted, the comparison may be of limited use because the two immunotherapy agents can have different indications and applications, depending on the clinical situation.
Trial data compared
Dr. Verneris and colleagues looked at patient-level data from two clinical trials: the phase 2 single-arm ELIANA trial evaluating tisagenlecleucel in patients with relapsed and refractory B-cell lineage ALL (79 patients), and the efficacy phase of the MT103-205 trial assessing blinatumomab in a similar population (70 patients).
To account for differences between the studies, the investigators used five different statistical approaches, including propensity score weighting and adjustment for prognostic factors.
Regardless of the analytical method they used, results showed that patients treated with tisagenlecleucel were significantly more likely to have complete remissions than were patients treated with blinatumomab, with odds ratios favoring the CAR T-cell construct ranging from 6.71 to 9.76.
Similarly, treatment with tisagenlecleucel was associated with lower risk for death, with hazard ratios ranging from 68% to 74%.
The authors acknowledged that some prognostic variables such as bone marrow blast count, remission duration, and performance status were not recorded in the patient level data from the blinatumomab trial and therefore they could not be used in the analyses. They also conceded that selection bias could account for some of the differences in outcomes between the trials.
Patient characteristics drive choice
The comparison of the two agents “is something we as treating physicians often think about, because we are faced with a choice often of tisagenlecleucel or blinatumomab when we have a relapsed/refractory patient, ” Melinda Pauly, MD, medical director of oncology at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, said in an interview.
Courtesy CHOA
Dr. Melinda Pauly
Dr. Pauly, who was not involved in the study, said that the choice of therapy is based primarily on patient characteristics and the specific clinical situation.
“For patients who have prior toxicity with bone marrow transplant or don’t have a good donor option for bone marrow transplant, those are certainly patients that we are looking for a therapy that would be more sustained, and that would definitely be the tisagenlecleucel,” she said.
CAR T-cell therapy may not be an immediate option for patients for whom time is critical, however, due to the requirements of apheresis for T-cell harvesting, cell transduction, expansion, and infusion, and for such patients who have disease refractory to chemotherapy, blinatumomab may be an option.
Blinatumomab may also serve as a bridge to transplant, she said.
Dr. Pauly, who has a special interest in the care of infants with ALL, noted that apheresis can be difficult to accomplish in very young patients and may not yield T-cells sufficient for CAR T therapy, and for these patients blinatumomab may be the better option.
Howard Weinstein, MD, unit chief of the division of pediatric hematology/oncology at Mass General Hospital for Children in Boston, noted that “there are all kinds of statistical methodologies to try to balance the two populations in the studies, and they did as best as you can at balancing the risk factors, such as the number of patients with relapses after prior bone marrow transplants.”
Courtesy Massachusetts General Hospital
Dr. Howard Weinstein
“But there are so many genetic subtypes of acute lymphoblastic leukemia that have differing prognoses, it’s hard to do this kind of retrospective analysis when it’s not a randomized head-to-head trial,” he said in an interview.
Novartis Pharmaceuticals, maker of tisagenlecleucel, sponsored the study. Dr. Verneris disclosed serving on advisory boards for Novartis, and five of the study coauthors are employees of the company. Dr. Pauly and Dr. Weinstein reported having no conflicts of interest.