Axicabtagene ciloleucel (axi-cel; Yescarta) was approved by the FDA for the treatment of adult patients with large B-cell lymphoma (LBCL) whose disease was refractory to or which relapsed within 12 month after first-line chemoimmunotherapy, according to a press release from the FDA.

Results of the phase 3 ZUMA-7 trial (NCT03391466)

, which examined axi-cel vs standard-of-care (SOC) in patients with relapsed/refractory LBCL, supported the approval. At the 

2021 American Society of Hematology Annual Meeting

, investigators reported a statistically significant event-free survival (EFS) improvement in those treatment in the active therapy arm.

At a median follow-up of 24.9 months, findings showed that the median EFS for patients treated with axi-cel and SOC were 8.3 months (95% CI, 4.5-15.8) and 2.0 months (95% CI, 1.6-2.8), respectively (HR, 0.398; 95% CI, 0.308-0.514; 

 <.0001). The corresponding 2-year EFS rates were 40.5% (95% CI, 33.2%-47.7%) and 16.3% (95% CI, 11.1%-22.2%) in each respective group.

Updated findings showed that independent review committee–assessed best objective response rate was significantly improved with axi-cel at 83% (95% CI; 77%-88%) vs 50% (95% CI; 43%-58%) with SOC.

Standard of care in the second-line curative setting is salvage chemotherapy followed by consolidation high-dose therapy (HDT)–autologous stem cell transplant (ASCT). However, many patients with poor prognosis are unable to compete therapy. In ZUMA-7, about 35% of patients in the SOC arm went on the receive on-protocol ASCT. Lack of chemotherapy response was most cited as a reason for not receiving ASCT.

Axi-cel is already approved for use to treat numerous hematologic malignancies, including indications in diffuse large B-cell lymphoma and follicular lymphoma. The treatment carries a boxed warning for cytokine release syndrome and neurologic toxicities, which are common adverse effects associated with this class of therapy.

The recommended dose of axi-cel in 2 × 10

 CAR-positive viable T cells/kg, with a maximum of 2 × 10

FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed April 1, 2022. https://bit.ly/3LAUUFD

Locke F, Miklos DB, Jacobson CA, et al. 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. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 2.

Articles

Based on results of the ZUMA-7 trial, the FDA approved axicabtagene ciloleucel for the treatment of certain patients with large B-cell lymphoma who received chemoimmunotherapy in the frontline setting. 

FDA Grants Approval to Axi-Cel for Adults With LBCL Following First-Line Chemoimmunotherapy 

Axicabtagene Ciloleucel for Relapsed/Refractory Large B-cell Lymphoma Following Chemoimmunotherapy 

Frederick Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as program co-leader of Immuno-Oncology at Moffitt Cancer Center in Tampa, Florida, spoke to CancerNetwork® about further research of axicabtagene ciloleucel (Yescarta; axi-cel) for patients with large B-cell lymphoma (LBCL).

 for patients pretreated with chemoimmunotherapy in the frontline setting and who relapsed within 12 months based on the phase 3 ZUMA-7 trial (NCT03391466) which compared axi-cel with standard of care therapy.

Axi-cel is a CAR T-cell therapy and one of the things that we don’t fully understand is why does CAR T-cell therapy does not work for more patients [with LBCL]. It targets CD19 on the surface of the cells, but the loss of CD19 does not seem to be a dominant mechanism for the tumor to evade CAR T-cell therapy. We need to figure out why patients progress even though they’ve been given CAR T-cell therapy. Once we understand that, we can design better CAR T-cell therapies. There are other ways to intervene, that includes either dual targeting against not just CD19, but other targets on the cell surface. We’re also looking at off-the-shelf or allogenic donor CAR T-cells which can be accessed easier and be given to the patient quicker. We’re looking at other strategies using other natural killer cells and gamma delta T-cells with other ways to get therapy quickly to the patients that can work best.

FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed April 8, 2022. https://bit.ly/3LAUUFD

Locke F, Miklos DB, Jacobson CA, et al. 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. 

. 2021;138(suppl 1):2. doi:10.1182/blood-2021-148039

Videos

Frederick Lock, MD, spoke about how future research regarding axicabtagene ciloleucel for patients with large B-cell lymphoma will progress.

Frederick Locke, MD, Reviews the Next Steps for Axi-Cel in LBCL

Frederick Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as program co-leader of Immuno-Oncology at Moffitt Cancer Center in Tampa, Florida, spoke to CancerNetwork® about the use of axicabtagene ciloleucel (Yescarta; axi-cel) for patients with relapsed/refractory large B-cell lymphoma (LBCL) has improved survival. Recently, the 

therapy was approved for patients who were pretreated with frontline chemoimmunotherapy

 and relapsed within 12 months based on the phase 3 ZUMA-7 trial (NCT03391466),

 which compared axi-cel with standard of care, with a median event-free survival improvement of 8.3 months (95% CI, 4.5-15.8) vs 2.0 (95% CI, 1.6-2.8) with standard of care (HR, 0.398; 95% CI, 0.308-0.514; 

This approval addresses an unmet need, which is patients who relapse within 12 months of initial therapy. Patients with LBCL who progress within 12 months of initial therapy have overall poorer outcomes. We now know that if we can get them CAR T-cell therapy with axi-cel as a second-line treatment, we’re ultimately offering the best treatment for the patients earlier. On the trial that led to this approval for axi-cel in the second line, 40% of patients who were randomized to receive axi-cel remain without progression, alive, and not needing other therapy 2 years after the treatment. That’s compared with 16% of patients who went down the path of chemotherapy and if they responded, got an autologous transplant. The key here is that we should give the best treatment available to patients earlier in the disease course. That requires early referral.

Frederick Lock, MD, spoke about how axicabtagene ciloleucel has improved survival in patients with large B-cell lymphoma.

Frederick Locke, MD, Talks Unmet Needs Reduced by Axi-Cel Use in LBCL

Frederick Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as program co-leader of Immuno-Oncology at Moffitt Cancer Center in Tampa, Florida, spoke to CancerNetwork® about the recent approval of axicabtagene ciloleucel (Yescarta; axi-cel) for patients with large B-cell lymphoma (LBCL) whose disease relapsed or was refractory to frontline chemoimmunotherapy.

 The approval was based on data from the phase 3 ZUMA-7 trial (NCT03391466), which compared axi-cel with standard of care.

The recent approval of axi-cel as second-line treatment for LBCL is critical. It’s going to mean that hopefully more patients will be getting this potentially lifesaving therapy. The therapy is already approved for the third or later line in patients with relapsed/refractory LBCL. This new approval allows its use in the second-line setting. This is different than the prior standard of care, which was for patients to get a multi-agent chemotherapy regimen. There was [no regimen] that was better than another; [it was] dealer’s choice of chemotherapy regimens. Then only the patients who responded to chemotherapy would get consolidated with a autologous hematopoietic stem cell transplant. In that treatment paradigm, chemotherapy followed by transplant can only eradicate lymphoma in 20% of patients at best.

Now we know that CAR T-cell therapy with axi-cel as the second-line treatment as a single infusion for a patient with LBCL could get rid of the lymphoma where it hasn’t relapsed. In 40% of the patients, they haven’t needed any other therapy. [We’ve seen] remarkable results in the trial that led to this approval. It means that if you have a patient with LBCL who needs second-line therapy, the best bet for them if they relapse within 12 months of initial therapy [is to get] CAR T-cell therapy next, and the data is convincing to me.

1. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed April 8, 2022. https://bit.ly/3LAUUFD

2. Locke F, Miklos DB, Jacobson CA, et al. 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. Blood. 2021;138(suppl 1):2. doi:10.1182/blood-2021-148039

Frederick Lock, MD, spoke about the approval of axicabtagene ciloleucel and how it’s beneficial for patients with large B-cell lymphoma who were treated with frontline chemoimmunotherapy. 