Some of the most anticipated presentations at the 63rd Annual American Society of Hematology (ASH) Meeting and Exposition involve phase 3 results for chimeric antigen receptor (CAR) T-cell therapy in second-line treatment.
In 2017, FDA approved the first chimeric antigen receptor (CAR) T-cell therapies, tisangenlecleucel (tisa-cel), sold as Kymriah, and axicabtagene cilocleucel (axi-cel), sold as Yescarta, for patients with B-cell lymphomas treated with at least 2 prior therapies.
Not long after the question arose: would patients have better responses if they received CAR T-cell therapy earlier?
It’s a question that will get some answers during the 63rd Annual American Society of Hematology Meeting and Exposition, which takes place December 11-14 in Atlanta and online. Some of the most anticipated presentations at ASH involve phase 3 results for CAR T-cell therapy in second-line treatment, and there are also phase 2 results for axi-cel in the first-line setting coming Monday.
Given the cost of CAR T-cell therapy, which lists for $373,000 to $475,000, depending on the indication, the answer is important to payers, who want to know if these expensive processes are more likely to succeed if patients are treated when their immune systems are less depleted. CAR T-cell therapy works by harnessing the patient’s own immune system to fight cancer cells.
There’s also the issue of avoiding the cost of prior treatments. However, Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research, said during a keynote address in October that widespread use of CAR T-cell therapy at earlier stages might only come if the cost of these treatments came down significantly.
Second-line treatment in LBCL. Two presentations will address this, led by the primary analysis of ZUMA-7, the phase 3 randomized trial that examines the use of axi-cel vs second-line standard of care in relapsed/refractory large B-cell lymphoma (LBCL). Gilead Sciences, which sells axi-cel as Yescarta, announced in June that results showed axi-cel offered a 62% event-free survival benefit over chemotherapy and stem-cell transplant. Results will be presented in Sunday’s plenary session by Frederick Locke, MD, of Moffitt Cancer Center. Axi-cel is currently approved for LBCL or follicular lymphoma when patients have received at least 2 other therapies.
The race is already on for use of axi-cel in the first-line stage, with phase 2 results from ZUMA-12 to be presented by Sattva S. Neelapu, MD, of MD Anderson Cancer Center.
Getting a jump on ZUMA-7 will be a Saturday morning presentation on interim findings from the phase 3 TRANSFORM study involving lisocabtagene maraleucel (liso-cel), which was approved earlier this year for patients with certain types of LBCL who have received at least 2 treatments. Sold as Breyanzi, liso-cel has a different manufacturing process that investigators say results in less toxicity than earlier CAR T-cell therapies. Officials from Bristol Myers Squibb also announced a significant benefit based on early results; the prespecified interim analysis to be presented at ASH shows event-free survival of 10.1 months, while overall survival data are immature.
Results for tisa-cel in the second-line setting will be presented in the late-breaking session Tuesday, but Novartis announced in August that the BELINDA study did not meet its end point.
Biomarkers and CAR T-cell therapy. Payers will be interested in the effort by 12 academic institutions to track molecular features for 121 patients with diffuse LBCL and assess which biomarkers had effects on clinical outcomes after the patients were later treated with tisa-cel or axi-cel. This study promises to identify possible targetable pathways to bring better responses to CAR T-cell therapy and identify which patients will have the best outcomes.
MCL in real-world settings. FDA approved brexucabtagene autoleucel (brexu-cel) in mantle cell lymphoma (MCL) in July 2020, based on results from the ZUMA-2 trial that showed a 90% objective response rate (ORR) and a 67% complete response rate (CR). A study to be presented by the US Lymphoma Consortium leverages the use of real-world data to show that patients with MCL who fell outside the ZUMA-2 criteria have reported high safety and efficacy rates when treated with brexu-cel.
Beyond R-CHOP. For patients with previously untreated LBCL, there will still be choices beyond CAR T-cell therapy. Results from Tuesday morning’s late-breaking abstracts will start with the phase 3 POLARIX study, which examines the use of polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone, or pola-R-CHP, vs the well-known combination of rituxiumab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated diffuse LBCL.
A discussion, “Novel Findings in CAR T-Cell Therapies for Hematologic Malignancies,” with a live question and answer session, will take place Monday from 4:30 to 5:15 pm. The session chair will be Marcela V. Maus, MD, Massachusetts General Hospital and Harvard Medical School; panelists will be Maus; David Baker, PhD, University of Washington; and Marco Ruella, MD, University of Pennsylvania.