What’s new in the field of hematologic cell and gene therapy: Part III

Julianne Dunphy, PhD, Global Director, Medical Strategy at Mind+Matter, part of EmerGENE, shares a series of standout findings presented at the 63rd American Society of Hematology (ASH) annual meeting and exposition in December 2021.

In this final segment of insights from attending ASH, Julianne delves into new discussions on CAR-T therapies and how their place in therapy might be shifting. Find part I and II of this blog series here.

Driving CAR-T therapies up the line

The efficacy and safety of CAR-T therapies in hematologic malignancies have been well established in later lines of treatment where the standard of care is less firm. Now, results from the large phase 3 ZUMA-7 trial of Gilead’s axicabtagene ciloleucel (axi-cel; Yescarta) and other data (of note BMS’ TRANSFORM trial of lisocabtagene maraleucel (liso-cel)) show that CD19 CAR-T cell therapy has the potential to change that[i]. Both studies demonstrated superior efficacy vs. 2^nd-line standard of care in aggressive relapsed or refractory large B cell lymphoma (LBCL) and in the case of axi-cel, a greater proportion of patients maintained this effect at 2 years compared to standard of care treatment. Both studies also suggest an improvement in QoL associated with the treatment.

Given that standard of care in this setting is generally high-dose chemotherapy followed by transplant, the potential impact of these results is striking. Moving up a line in therapy significantly increases the number of patients who would be candidates for CAR-T cell therapy. Furthermore, not all patients are not eligible for current second-line standard of care, further increasing these treatments’ value in this earlier setting. Indeed Dr. Locke stated that “results from the ZUMA-7 trial herald a paradigm shift: axi-cel should be a new standard” in this treatment setting. Transplant isn’t going away any time soon, but the results did raise the question. As one attendee mused, is CAR-T treatment the “new transplant”? Overall, the excitement during the conference was palpable and stimulated discussion and debate into the subsequent weeks.

And a note about equity in clinical trials

In the Q&A session following the ZUMA-7 presentation, questions were raised around the ethnic makeup of the patients in the clinical trial. The response was that the participating patients, as with many clinical trials, were not epidemiologically representative of the real-world patient populations. The reply was then that perhaps such a trial should therefore not be included in the prestigious Plenary Session.

This discussion is indicative of a broader concern relating to health equity in clinical trials, which has received increasing attention in recent years as it is invariably inadequate. Diversity, equity, and inclusion were important and prominent topics at ASH and were the subject of several sessions and abstracts. As Indianapolis oncologist, Dr Ruemu Birhiray, noted: “We have to do better.”

Discover EmerGENE

At EmerGENE, we are committed to exploring the latest advancements in C&GT to guide our customers in getting these life-changing treatments to patients. None of these studies could be done without the generous support and participation of the patients and caregivers and are the driving force behind what we do as well. For further insights, please click here.

References

[i] Jeremy S. Abramson, et al: 3845 Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study. Abstract available at: https://ash.confex.com/ash/2021/webprogram/Paper151611.html

Mahmoud Elsawy, et al: 430 Patient-Reported Outcomes in a Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard of Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma (ZUMA-7). Abstract available at: https://ash.confex.com/ash/2021/webprogram/Paper147598.html

Manali Kamdar, et al: 91 Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform Study. Abstract available at: https://ash.confex.com/ash/2021/webprogram/Paper147913.html

Frederick L. Locke, et al: 2 Primary Analysis of ZUMA‑7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard‑of‑Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma. Abstract available at: https://ash.confex.com/ash/2021/webprogram/Paper148039.html