CAR T-cell therapies for lymphoma shine at ASH blood cancer conference

Dec 21, 2021

CAR T-cell therapies for lymphoma shine at ASH blood cancer conference

Two CAR T-cell therapies are already approved for B-cell lymphoma, but data indicates they should be used earlier in the treatment process – good news for expanding patient access to these life-saving therapies.

The 63rd annual conference of the American Society of Hematology (ASH) was held Dec. 11-14 at the Georgia World Congress Center in Atlanta. The meeting featured multiple presentations highlighting the progress of cell and gene therapy for blood cancers like lymphoma.

Clinical and follow-up data on patients treated with Yescarta® (Axicabtagene Ciloleucel) and Breyanzi ® (Lisocabtagene Maraleucel), two approved CAR T-cell therapies for blood cancers, were some of the highlights from the conference.

What are Yescarta® and Breyanzi®?

Yescarta and Breyanzi are CAR T-cell therapies, and they are already approved for certain patients with B-cell lymphoma. The U.S Food and Drug Administration (FDA) approved Yescarta (brand name of axicabtagene ciloleucel, or “axi-cel”) for non-Hodgkin lymphoma as a third-line therapy. Third-line therapy means two prior treatment attempts must have failed. 

Breyanzi (brand name of lisocabtagene maraleucel, or “liso-cel”) is also a third-line option for B-cell lymphoma. 

Like other CAR T-cell therapies, Yescarta and Breyanzi help detect previously undetectable blood cancer cells by adding chimeric antigen receptors (CARs) to a patient’s existing T cells. Both engineer the body’s T cells to look for CD19, which is a protein antigen associated with B-cell lymphoma.

Data presented at ASH conference

Two clinical trials, ZUMA-7 and TRANSFORM, studied Yescarta, from Kite, a Gilead company, and Breyanzi from Bristol Myers Squibb, respectively. Both therapies performed exceptionally, outdoing the standard second-line treatment combination of chemotherapy plus a stem-cell transplant:

  • Yescarta’s event-free survival was 8.3 months, versus 2.0 for standard care.
  • Breyzani’s event-free survival was 10.2 months, versus 2.3 for standard care.
  • Yescarta reached 61% two-year survival rate, up from 52% for chemotherapy with stem-cell transplantation.
  • Breyanzi showed progression-free survival of 14.8 months, more than double standard care (5.7).

Frederick L. Locke, MD, of Moffitt Cancer Center, commented at the ASH conference about ZUMA-7’s success.

“Nearly three times the number of patients in the axi-cel (Yescarta) arm received definitive therapy versus the standard-of-care arm,” he said in a press briefing. “Axi-cel had a manageable safety profile consistent with previous studies.”

Several other presentations featured CAR T-cell therapies for blood cancers. Some of them are below:

  • MB-106, a CD20-targeting CAR T-cell therapy from Mustang Bio, posted a 95% overall response rate and 65% complete response rate in an early phase trial for B-cell lymphoma and chronic lymphocytic leukemia.
  • Yescarta had an 89% overall response rate and 78% complete response rate as a first-line therapy for large B-cell lymphoma. The phase 2 trial has an estimated 92% one-year survival rate.
  • Ciltacabtagene autoleucel (cilta-cel) from Janssen and Legend Biotech, led to a 98% response rate and 82.5% complete response rate for patients with relapsed or refractory multiple myeloma. The two-year survival rate in the early phase study was an impressive 74%. Cilta-cel is reportedly close to FDA approval for these advanced cases of multiple myeloma.

What does this mean for advancing CAR T-cell therapy?

In the short term, the success of these phase 3 trials means there’s a good chance both Yescarta and Breyanzi will be approved by the FDA as a second-line therapy for B-cell lymphoma. Phase 3 is a vital stage in the clinical process: better survival and safety results than standard care therapies will usually result in an FDA approval. 

If approved as second-line treatment for B-cell lymphoma, CAR T-cell therapy may provide patients with significantly better outcomes both in the short-term, following treatment, but also in long-term quality of life. Patients will be exposed to less high-dose chemotherapy, which can have limited benefit for many patients.

“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” said Laurie Sehn, MD, MPH, of the BC Cancer Agency for Lymphoid Cancer in Vancouver, Canada.

She added the second-line approach of “more chemotherapy and at higher doses” often doesn’t work. Dr. Sehn is not surprised “a novel approach and a cellular therapy” outperformed chemotherapy.

Larger message about cancer cell and gene therapy

Long-term, this news has an effect for more than just people with blood cancers. Alliance for Cancer Gene Therapy championed CAR T-cell therapy for blood cancers at the beginning of the century – and our support opened the doors for the first FDA approvals, and first patient survivor stories. The most impactful way to make cancer cell and gene therapy more accessible to patients is to continue to build a pipeline of research that leads to successful clinical trials and new product approvals. 

The potential for CAR T-cell therapies and other cell and gene therapies to succeed in solid tumors, such as pancreatic cancer and brain cancer – the current focus of Alliance for Cancer Gene Therapy (ACGT). 

With the support of our donors, ACGT is driving breakthroughs in cell and gene therapy research to develop more innovative treatments to defeat all cancers. Today, these breakthrough FDA-approved CAR T-cell therapies for blood cancers, including Yescarta and Breyanzi, are changing lives thanks to our early funding. 

A donation to ACGT supports our mission and will allow us to fund ground-breaking research that will lead to more life-changing cancer cell and gene therapies for patients. Please consider a gift to the Alliance as we continue creating a hopeful future for people diagnosed with cancer. 

Page sources

  1. CAR T-Cell Therapy Makes Strong Case for Earlier Use in Lymphoma. Medpage Today. Retrieved from: https://www.medpagetoday.com/meetingcoverage/ashhematology/96150. Accessed: 12/13/2021.
  2. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. The New England Journal of Medicine. Accessed: https://www.nejm.org/doi/full/10.1056/NEJMoa2116133. Accessed: 12/13/2021.
  3. ‘Remarkable’ Results With CAR T Cells Could Make Chemo Obsolete. Medscape. Retrieved from: https://www.medscape.com/viewarticle/964646. Accessed: 12/13/2021.
  4. Treatment With Cilta-Cel Continues Yield Robust, Long-Lasting Outcomes in Relapsed/Refractory Multiple Myeloma. Cancer Network. Retrieved from: https://www.cancernetwork.com/view/treatment-with-cilta-cel-continues-yield-robust-long-lasting-outcomes-in-relapsed-refractory-multiple-myeloma. Accessed: 12/14/2021
  5. Mustang Bio Announces Updated Interim Phase 1/2 Data for MB-106 in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. Mustang Bio. Retrieved from: https://ir.mustangbio.com/News/news-details/2021/Mustang-Bio-Announces-Updated-Interim-Phase-12-Data-for-MB-106-in-Patients-with-Relapsed-or-Refractory-B-cell-Non-Hodgkin-Lymphoma-and-Chronic-Lymphocytic-Leukemia/default.aspx. Accessed: 12/14/2021.