Updated trial data shows that Opdivo had a high objective response rate for a cohort of patients with classical Hodgkin Lymphoma.
Opdivo (nivolumab) had a 73 percent objective response rate (ORR) for patients with classical Hodgkin lymphoma (cHL) who received Adcetris (brentuximab vedotin) before and/or after autologous hematopoietic stem cell transplantation (AHSCT), according to updated results from the CheckMate-205 trial.
The updated data are consistent with prior results from a separate CheckMate-205 cohort which supported the FDA’s May 2016 approval of Opdivo for patients with cHL who relapse or progress after AHSCT and post-transplantation Adcetris. 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, M.D., 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 2 CheckMate-205 trial included three primary cohorts: 63 patients who received AHSCT but were Adcetris —naïve (cohort A); 80 patients treated with AHSCT followed by Adcetris (cohort B); and 100 patients who received Adcetris before and/or after AHSCT (cohort C). A fourth cohort (D), which is now enrolling patients, is examining Opdivo combined with chemotherapy as a frontline regimen in newly diagnosed patients with advanced cHL.
All patients in the trial received Opdivo at 3 mg/kg IV every two weeks until progression or unacceptable toxicity. Patients in cohort C were also treated until complete response (CR) lasting one 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 percent (73 patients) ORR in this cohort was observed after a median follow-up of 8.8 months and was consistent regardless of the timing of Adcetris relative to AHSCT. In patients who received Adcetris before AHSCT, after AHSCT, or both, the ORR was 70 percent, 72 percent and 88 percent, respectively.
The CR rate was 17 percent (17 patients) in the overall cohort C population and the partial response (PR) rate was 56 percent (56 patients). The median duration of response was seven months. The six-month progression-free survival (PFS) rate, six-month overall survival (OS) rate, and median PFS were 76.6 percent, 93.9 percent and 11.2 months, respectively.
Among patients receiving Adcetris before AHSCT, the CR and PR rates were 18.2 percent (six patients) and 51.5 percent (17 patients), respectively. The median duration of response was seven months. The six-month PFS rate, six-month OS rate and median PFS were 83.7 percent, 97 percent, and 11.2 months respectively.
The CR and PR rates in patients receiving Adcetris after AHSCT were 12.3 percent (seven patients) and 59.6 percent (34 patients), respectively. The median duration of response was not available. The six-month PFS rate, six-month OS rate, and median PFS were 71.2 percent, 91 percent, and 8.9 months respectively.
In patients who received Adcetris before and after AHSCT, the CR rate was 38 percent (three patients) and the PR rate was 50 percent (four patients). The median duration of response was not available. The six-month PFS and six-month OS rates were 83.3 percent and 100 percent, 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 Opdivo in cHL, according to Bristol-Myers Squibb, the manufacturer of Opdivo.
“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, M.D., head of development, Oncology, Bristol-Myers Squibb, said in a statement.
Previously reported data from cohort B, in which all patients received Adcetris after AHSCT, were used to support the FDA approval of Opdivo in cHL. In findings from the cohort presented at the 2016 ASCO Annual meeting, Opdivo had an ORR of 66 percent, including seven CRs (8.8 percent) and 46 PRs (57.5 percent). The 6-month PFS and OS rates were 76.9 percent and 99 percent, respectively. The median PFS was 10 months.
All-grade treatment-related adverse events (AEs) were reported for 90 percent of patients (72 patients). The most common all-grade AEs were fatigue (25 percent), infusion reaction (20 percent), rash (16 percent), pyrexia (14 percent), arthralgia (14 percent), nausea (13 percent), diarrhea (10 percent) and pruritus (10 percent).
Twenty-five percent of patients (20 patients) 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 percent or less of patients.
In Europe, the Committee for Medicinal Products for Human Use has recommended approval of Opdivo for the treatment of patients with relapsed/refractory cHL after autologous stem cell transplant and treatment with Adcetris. The positive opinion is now being reviewed by the European Commission for a final approval decision.