Brentuximab Vedotin Boosts Survival in Adult and AYA Patients with Advanced Hodgkin Lymphoma

Ann S. LaCasce, MD, MMSC

Findings from recent studies have demonstrated the value of brentuximab vedotin (Adcetris) in both adult and adolescent and young adult (AYA) patients with advanced Hodgkin lymphoma, Ann S. LaCasce, MD, MMSC, said during a presentation at the 2022 Pan Pacific Lymphoma Conference.¹

The FDA first approved brentuximab vedotin for adults with relapsed/refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma (sALCL) in 2011. That decision that changed the treatment landscape for this disease, said LaCasce, director, Dana-Farber/Mass General Brigham Fellowship in Hematology/Oncology; chair, Fellowship Program in Hematology/Oncology, institute physician and associate professor of medicine, Harvard Medical School.

The agency subsequently expanded the indication for the anti-CD30–directed antibody-drug conjugate, most recently in 2018 when the agent was approved in combination with chemotherapy for adults with previously untreated stage III/IV classical Hodgkin lymphoma.² In data from the phase 3 ECHELON-1 trial (NCT01712490), brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) induced a 2-year modified progression-free survival (PFS) rate of 82.1% (95% CI, 78.8%-85.0%) compared with 77.2% (95% CI, 73.7%-80.4%) for patients assigned to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; HR, 0.77; 95% CI, 0.60-0.98; P = .04).³

Investigators recruited 1334 patients into the trial, who were then randomly assigned to up to 6 cycles of A+AVD (n = 664) or ABVD (n = 670) intravenously on days 1 and 15 every 28 days.

In updated results collected at a median follow-up of 73 months and presented at the 2022 ASCO Annual Meeting, 6-year PFS estimates were 82.3% (95% CI, 79.1%-85.0%) with A+AVD vs 74.5% (95% CI, 70.8%-77.7%) with ABVD, respectively (HR, 0.68; 95% CI, 0.53-0.86; P = .002). A total of 112 PFS events occurred in the A+AVD arm compared with 159 in the ABVD arms.⁴

The estimated 6-year overall survival rates were 93.9% (95% CI, 91.6%-95.5%) with A+AVD vs 89.4% (95% CI, 86.6%-91.7%) with ABVD (HR 0.59; 95% CI, 0.40-0.88; P = .009). The median OS was not yet reached in either arm.

There were 14 secondary solid tumors in each treatment arm. However, LaCasce noted that investigators recorded fewer secondary hematologic malignancies in the A+AVD arm (9 vs 17).

“Most of these were lymphomas, actually. There were some myeloid diseases,” she said. “It’s not clear why this would be lower with brentuximab [vedotin]. Is this just chance with smaller numbers? Or is there really a signal here that by giving brentuximab [vedotin] perhaps you’re preventing subsequent non-Hodgkin lymphoma?”

Positive Pediatric Results from AHOD1331

“We don’t talk a lot about the pediatric regimens in adult oncology,” LaCasce said. “We’re not familiar with them, they have these longer acronyms—but I thought the results of this study were actually quite, quite impressive.”

Investigators in the multicenter, randomized, open-label, phase 3 AHOD1331 trial (NCT02166463) sought to assesses the value of brentuximab vedotin plus doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVE-PC) vs the standard pediatric dose intensive regimen of bleomycin plus AVE-PC (ABVE-PC) in AYA patients with Hodgkin lymphoma. Patients aged 2 to 21 years were randomly assigned to 5 cycles of ABVE-PC (n = 289) or Bv-AVE-PC (n = 298) every 21 days with granulocyte colony-stimulating factor (G-CSF) support.⁵

Investigators conducted PET-CT after 2 cycles to identify slow responding lesions (SRLs). Those with bulky mediastinal adenopathy or SRLs received involved site radiotherapy.

The median patient age was 15.6 years, and roughly 57% of patients in both cohorts were non-Hispanic White. Consistent with a high-risk population, 71% of patients had B symptoms, and about half of patients on each group had large mediastinal adenopathy.

In the intent-to-treat analysis at a median follow-up of 42 months, event-free survival (EFS) was 92.1% (95% CI, 88.4%-94.7%) in the experimental arm vs 82.5% (95% CI, 77.4%-86.5%) for the control (HR, 0.41; 95% CI, 0.25-0.67; P = .0002). “There’s a 10% difference—82.5% vs 92%—which is highly statistically significant, and I think, a quite impressive outcome. And again, they got 5 cycles,” LaCasce said.

Bv-AVE-PC induced superior 3-year EFS outcomes for patients who were SRL-positive (90.7% vs 68.3%; HR, 0.28; 95% CI, 0.1-0.8) and those who were SRL-negative (92.3% vs 85.7%; HR, 0.48; 0.3-0.8). “Those are…significantly better numbers than we would expect with escalated BEACOPP [bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone] in [the phase 3] RATHL [trial (NCT00678327)] or in our other studies in adults,” LaCasce said. “For those of us who treat a lot of AYA patients, I think it will be interesting to discuss whether we should be using this regimen.”

References

1. LaCasce AS. Advanced stage Hodgkin lymphoma. Presented at: 2022 Pan Pacific Lymphoma Conference; July 18-22, 2022; Koloa, Hawaii.
2. Brentuximab vedotin. FDA. March 20, 2018. Accessed July 20, 2022. https://bit.ly/3zl2MI4
3. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018;378(4):331-344. doi:10.1056/NEJMoa1708984
4. Ansell SM, Connors JM, Radford JA, et al. First-line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: an updated analysis of ECHELON-1. J Clin Oncol. 2022;40(suppl 16):7503. doi:10.1200/JCO.2022.40.16_suppl.7503
5. Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin and association with event-free survival (EFS) in children with newly diagnosed high-risk Hodgkin lymphoma (HL): A report from the Children's Oncology Group phase 3 study AHOD1331 (NCT 02166463). J Clin Oncol. 2022;40(suppl 16):7504. doi:10.1200/JCO.2022.40.16_suppl.7504