Dr Riedell agreed that this may be one potential reason that influenced product selection in the study, but pointed out that likely many factors that play a role. “Additionally, the intensity of the lymphodepleting chemotherapy platform is less with tisa-cel versus axi-cel and this conceivably could have influenced decision making, especially when considering this treatment in patients of older age,” he added in an email.
Dr Riedell and his colleagues also examined efficacy and safety outcomes for both products, finding that they generally fell in line with those reported in pivotal clinical studies. The 90-day complete response (CR) rate for tisa-cel in Dr Riedell’s study was 42%, compared with 40% in the JULIET trial.2 For axi-cel, Dr Riedell’s team observed a CR rate of 53%, compared with 58% in the ZUMA-1 trial.3
That is a good sign, particularly as 50% of axi-cel patients, and 30% of tisa-cel patients, would not have been eligible for the ZUMA-1 and JULIET studies, respectively, most frequently due to inadequate bone marrow reserve, blood count abnormalities, and depressed renal function. To Dr Riedell and Dr Cooper, this underscores the idea that clinical eligibility criteria are overly stringent.
Also noteworthy was the fact that 24% of tisa-cel patients received a product that was deemed out-of-specification for commercial release, often because the cell products fell below the cell viability level of 80% — a level that is required by the US Food and Drug Administration. Recent research looking at outcomes of patients that had received the out-of-specification tisa-cel product found that clinical outcomes were similar.4 “We don’t think that there’s a meaningful difference in terms of the safety and efficacy profile in [those] patients,” Dr Riedell said.
Tisa-cel patients experienced better toxicity scores than axi-cel patients: 85% of axi-cel recipients experienced cytokine release syndrome of any grade, with 8% above grade 3, compared with 41% and 1% of tisa-cel recipients, respectively. And, 53% of axi-cel patients experienced neurological toxicities of any grade, with 33% experiencing toxicities higher than grade 3, compared with 14% and 0%, respectively, for tisa-cel patients. Dr Riedell cautioned that “it’s not comparing apples to apples,” because the patient populations differ.
“We still don’t know which is, overall, the better product in terms of causing the cure,” because of the different patient populations, Dr Cooper said. However, “it’s pretty clear that the [tisa-cel] is the milder, better-tolerated [product], and more easily able to transfer to the outpatient area than the Yescarta product.” He added that he found the nonrelapse mortality of axi-cel recipients — 9%, compared with 2% for tisa-cel patients —concerning, as it is higher than rates observed for autologous stem cell transplants.
It remains to be seen how the products will perform as they continue to move into the real world, Dr Cooper said, noting that the treatment centers that participated in Dr Riedell’s study were academic centers — in some cases, the same ones where pivotal clinical trials took place. “One of the questions is going to be [whether] we are going to see the same results when this is done in centers that aren’t academic.”
Disclosures: Dr Riedell serves as a speaker for Kite/Gilead, Bayer, and on the advisory board for Verastem, Novartis, Celgene/BMS, and Bayer. He has received honoraria from Novartis and institutional research support from Celgene/BMS, Kite/Gilead, and Novartis.
- Riedell PA, Walling C, Nastoupil LJ, et al. A multicenter retrospective analysis of outcomes and toxicities with commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed/refractory aggressive B-cell lymphomas. Presentation at: the 2020 Transplantation & Cellular Therapy Meetings of ASCT and CIBMTR; February 19-23, 2020; Orlando, FL. Abstract 52.
- Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56.
- Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42.
- Chong EA, Gerson JN, Landsburg DJ, et al. Outcomes in aggressive B-cell non-Hodgkin lymphomas with anti-CD19 CAR T-cell (CTL019) products not meeting commercial release specifications. Blood. 2019;134(Supplement_1):594.