New Data Sustain Strong Benefit for Nivolumab in Hodgkin Lymphoma

Andreas Engert, MD

Updated results from the CheckMate-205 trial showed that nivolumab (Opdivo) had an objective response rate (ORR) of 73% in a cohort of patients with classical Hodgkin lymphoma (cHL) who received brentuximab vedotin (Adcetris) before and/or after autologous hematopoietic stem cell transplantation (AHSCT).

The updated data are consistent with prior results from a separate CheckMate-205 cohort which supported the FDA’s May 2016 approval of nivolumab for patients with cHL who relapse or progress after AHSCT and posttransplantation brentuximab vedotin. The latest findings were presented at 10th International Symposium on Hodgkin Lymphoma (ISHL) in Cologne, Germany.

“These data…build on existing evidence supporting the benefit of Opdivo in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and posttransplantation brentuximab vedotin,” Andreas Engert, MD, study investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Germany, said in a statement.

“[The latest results] indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients,” added Engert.

The open-label phase II CheckMate-205 trial included 3 primary cohorts: 63 patients who received AHSCT but were brentuximab vedotin—naïve (cohort A); 80 patients treated with AHSCT followed by brentuximab vedotin (cohort B); and 100 patients who received brentuximab vedotin before and/or after AHSCT (cohort C). A fourth cohort (D), which is now enrolling patients, is examining nivolumab combined with chemotherapy as a frontline regimen in newly diagnosed patients with advanced cHL.

All patients in the trial received nivolumab at 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Patients in cohort C were also treated until complete response (CR) lasting 1 year as per investigator assessment. The primary endpoint was ORR per assessment by an independent radiologic review committee.

The data presented at the ISHL were the outcomes from cohort C. The 73% (n = 73; 95% CI, 63.2-81.4) ORR in this cohort was observed after a median follow-up of 8.8 months and was consistent regardless of the timing of brentuximab vedotin relative to AHSCT. In patients who received brentuximab vedotin before AHSCT, after AHSCT, or both, the ORR was 70% (23/33; 95% CI, 51.3-84.4), 72% (41/57; 95% CI, 58.5-83), and 88% (7/8; 95% CI: 47.3-99.7), respectively.

The CR rate was 17% (n = 17) in the overall cohort C population and the partial response (PR) rate was 56% (n = 56). The median duration of response was 7 months. The 6-month progression-free survival (PFS) rate, 6-month overall survival (OS) rate, and median PFS were 76.6%, 93.9%, and 11.2 months, respectively.

Among patients receiving brentuximab vedotin before AHSCT, the CR and PR rates were 18.2% (n = 6) and 51.5% (n = 17), respectively. The median duration of response was 7 months. The 6-month PFS rate, 6-month OS rate, and median PFS were 83.7%, 97%, and 11.2 months respectively.

The CR and PR rates in patients receiving brentuximab vedotin after AHSCT were 12.3% (n = 7) and 59.6% (n = 34), respectively. The median duration of response was not available. The 6-month PFS rate, 6-month OS rate, and median PFS were 71.2%, 91%, and 8.9 months respectively.

In patients who received brentuximab vedotin before and after AHSCT, the CR rate was 38% (n = 3) and the PR rate was 50% (n = 4). The median duration of response was not available. The 6-month PFS and 6-month OS rates were 83.3% and 100%, respectively. The median PFS was not available.

There were no new safety signals observed and the safety profile was consistent with previously reported results for nivolumab in cHL, according to Bristol-Myers Squibb, the manufacturer of nivolumab.

“We continue to expand our immuno-oncology science in hematology, and these latest results from CheckMate-205 will help inform our research into classical Hodgkin lymphoma and aid us in determining whether Opdivo may provide benefit to a broader population of patients living with this difficult-to-treat disease,” Fouad Namouni, MD, head of development, Oncology, Bristol-Myers Squibb, said in a statement.

Previously reported data from cohort B, in which all patients received brentuximab vedotin after AHSCT, were used to support the FDA approval of nivolumab in cHL. In findings from the cohort presented at the 2016 ASCO Annual meeting, nivolumab had an ORR of 66%, including 7 CRs (8.8%) and 46 PRs (57.5%). The 6-month PFS and OS rates were 76.9% and 99%, respectively. The median PFS was 10 months.

All-grade treatment-related adverse events (AEs) were reported for 90% of patients (n = 72). The most common all-grade AEs were fatigue (25%), infusion reaction (20%), rash (16%), pyrexia (14%), arthralgia (14%), nausea (13%), diarrhea (10%), and pruritus (10%).

Twenty-five percent of patients (n = 20) had grade 3/4 AEs. The most frequently occurring serious AEs included pyrexia, tumor progression, arrhythmia, infusion reaction, septic meningitis, and pneumonia, each of which occurred in 4% or less of patients.

In Europe, the Committee for Medicinal Products for Human Use has recommended approval of nivolumab for the treatment of patients with relapsed/refractory cHL after autologous stem cell transplant and treatment with brentuximab vedotin. The positive opinion is now being reviewed by the European Commission for a final approval decision.

Younes A, Santoro A, Zinzani PL, et al. Checkmate 205: Nivolumab (nivo) in classical Hodgkin lymphoma (cHL) after autologous stem cell transplant (ASCT) and brentuximab vedotin (BV)—A phase 2 study. J Clin Oncol 34, 2016 (suppl; abstr 7535).