Axi-cel Receives Positive Opinion from EU for DLBCL/HGBL

The European Medicines Agency Committee for Medicinal Products for Human Use has granted a positive opinion for axicabtagene ciloleucel for the treatment of adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion for axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.1

The positive opinion was based on findings from the phase 3 ZUMA-7 trial (NCT03391466), which showed that patients treated with axi-cel achieved a median event-free survival (EFS) of 8.3 months compared with 2.0 months for standard of care (SOC; HR, 0.40; 95% CI, 0.31-0.51; P < .001). Additionally, the 2-year EFS rates for the axi-cel and SOC arms were 41% and 16%, respectively.

“For people with DLBCL and HGBL who do not respond to first-line treatment or have an early relapse, outcomes are often poor and there are limited curative treatment options for these patients,” Marie José Kersten, MD, PhD, professor of hematology at Amsterdam University Medical Centers, stated in a press release. “If approved, axi-cel may offer a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in a randomized trial of axi-cel vs the current standard of care, quality of life also showed greater improvement in the experimental arm.”

The ongoing, open-label, global, multicenter ZUMA-7 trial is evaluating axi-cel vs SOC as second-line therapy for 359 adult patients with relapsed or refractory large B-cell lymphoma (LBCL) within 12 months of first-line therapy. First-line treatment needed to include of a minimum of an anti-CD20 monoclonal antibody unless the tumor was deemed CD20 negative, and an anthracycline-containing chemotherapy regimen.2

Patients needed to intend to proceed to high-dose chemotherapy with autologous stem cell transplant.3 Patients were not permitted to have received a prior autologous or allogeneic stem cell transplant.

Enrolled patients were randomly assigned 1:1 to receive a single infusion of axi-cel (n = 180) or SOC featuring two or three cycles of protocol-defined, investigator-selected, platinum-based chemoimmunotherapy (n = 179).

Along with the primary end point of EFS, secondary end points included objective response rate (ORR), overall survival (OS), modified EFS, progression-free survival, duration of response, and safety.

Additional data from ZUMA-7 showed that EFS benefits with axi-cel vs SOC were consistent across key subgroups of patients, including elderly patients (HR, 0.28; 95% CI, 0.16-0.46), primary refractory patients (HR, 0.43; 95% CI, 0.32-0.57), patients with HGBL including double-hit and triple-hit lymphoma (HR, 0.28; 95% CI, 0.14-0.59), and patients with double expressor lymphoma (HR, 0.42; 95% CI, 0.27-0.67).

Patients in the axi-cel arm achieved an ORR of 83% with a complete response (CR) rate of 65%, compared with an ORR of 50% and a CR rate of 32% for patients in the SOC arm. An interim analysis showed the estimated 2-year OS rates in the axi-cel and SOC groups were 61% and 52%, respectively.

In 170 safety-evaluable patients treated with axi-cel, grade 3 or higher cytokine release syndrome (CRS) occurred in 6% of patients, and grade 3 or higher neurologic events were observed 21% of patients. No Grade 5 CRS or neurologic events were reported. In the SOC arm, 83% of patients had high-grade events consisting primarily of cytopenias.

Patient-reported outcomes also demonstrated that patients treated with axi-cel (n = 165) reported statistically significant improvements in quality of life at day 100 compared with those given SOC (n = 131).

In April 2022, the FDA approved axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.4

In August 2018, the European Commission approved axi-cel as a treatment for adult patients with relapsed/refractory DLBCL or primary mediastinal LBCL following at least 2 lines of systemic therapy.5

References

  1. Kite’s CAR T-cell therapy Yescarta® first In Europe to receive positive CHMP opinion for use in second-line diffuse large B-cell lymphoma and high-grade B-cell lymphoma. News release. Gilead. September 16, 2022. Accessed September 19, 2022. https://bit.ly/3Ls6Uu4
  2. Efficacy of axicabtagene ciloleucel compared to standard of care therapy in subjects with relapsed/refractory diffuse large B cell lymphoma (ZUMA-7). ClinicalTrials.gov. Updated April 29, 2022. Accessed September 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03391466
  3. Locke F, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133
  4. 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/3iSQ8XT
  5. Yescarta® (axicabtagene ciloleucel) receives European marketing authorization for the treatment of relapsed or refractory DLBCL and PMBCL, after two or more lines of systemic therapy. News release. Gilead. August 27, 2018. Accessed September 19, 2022. https://bit.ly/3DAtIpL