June 6, 2016

Jason M. Broderick

Single-agent nivolumab induced responses in 66% of patients with classical Hodgkin lymphoma who had progressed following autologous stem cell transplant and brentuximab vedotin.

Anas Younes, MD

Single-agent nivolumab (Opdivo) induced responses in 66% of patients with classical Hodgkin lymphoma (cHL) who had progressed following autologous stem cell transplant (ASCT) and brentuximab vedotin (adcetris), according to findings from the phase II CheckMate-205 trial presented at the 2016 ASCO Annual Meeting.

The responses with nivolumab were durable and included 7 complete remissions (CR) and 46 partial remissions (PR). Among the 43 patients who did not respond to brentuximab vedotin, 72% (n = 31) responded to nivolumab. Based in part on data from the CheckMate-205 trial, the FDA previously granted nivolumab an accelerated approval for the treatment of patients with cHL in this setting in May 2016.

“CheckMate 205 demonstrated that nivolumab is an important new treatment for patients with cHL whose disease has progressed after autologous stem cell transplant and brentuximab vedotin,” lead author Anas Younes, MD, said in a video presentation included with his abstract poster at ASCO.

“The durability of both complete and partial responses was encouraging, with the majority of responses ongoing at the time of this analysis,” added Younes, who is chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center.

The overall CheckMate-205 trial evaluated nivolumab in both newly diagnosed and previously treated patients with cHL. Individuals enrolled in 1 of the study’s 3 pretreated patient cohorts (including the cohort Younes et al presented at ASCO) received 3 mg/kg of nivolumab as an IV injection every 2 weeks. The treatment-naïve patient cohort received 240 mg of nivolumab as an IV injection every 2 weeks plus 25 mg/m² of doxorubicin, 6 mg/m² of vinblastine, and 375 mg/m² of dacarbazine. The primary outcome measure was overall response rate (ORR).

The data Younes presented at ASCO were from the CheckMate-205 cohort that included 80 patients with cHL who had previously received ASCT and brentuximab vedotin. The median age of these patients was 37 years (range 18-72) and 96% of patients (n = 77) were aged <65 years. Sixty-four percent of patients (n = 51) were male, with 52.5% (n = 42) and 47.5% (n = 38) of patients having an ECOG performance status of 0 and 1, respectively.

Patients had received a median of 4 prior lines of therapy (range, 3-15) and 39 patients (49%) had ≥5 prior lines. Of the 80 patients, 74 (92.5%) had underwent 1 prior ASCT, and 6 (7.5%) had underwent ≥2 prior ASCT. All patients had received brentuximab vedotin, and 54% of patients (n = 43) did not have a response to the antibody-drug conjugate.

At a data cutoff in October 2015, the median follow-up was 8.9 months (95% CI, 1.9-11.7) and 64% of patients (n = 51) remained on treatment. Of the 36% of patients (n = 29) who stopped treatment, the reasons for discontinuation included progression (16%), toxicity (5%), proceeding to allogeneic stem cell transplant (6%), proceeding to ASCT (1%), and other (8%). All of the 6 patients who opted to end nivolumab treatment and undergo stem cell transplant were alive at the data cutoff.

ORR by independent radiologic review was 66% (n = 53; 95% CI, 54.8-76.4), which included a CR rate of 8.8% (95% CI, 3.6-17.2) and a PR rate of 57.5% (95% CI, 45.9-68.5). Of these responders, 62% (n = 33) remained in response at the data cutoff. Eighteen patients (23%) had stable disease (SD), 6 patients (8%) had progressive disease, and the status was unable to be determined for 3 patients (4%). The median time to response was 2.1 months (range, 1.6-5.7) and the median duration of response was 7.8 months (95% CI, 6.6 to not estimable).

The 6-month progression-free and overall survival rates per independent review were 76.9% (95% CI, 64.9-85.3) and 99%, (95% CI, 91-100) respectively. The median PFS was 10 months (95% CI, 8.4 to N/A).

The investigator assessed ORR was 73% (n = 58; 95% CI, 61.4-81.9), which included CR and PR rates of 27.5% (n = 22; 95% CI, 18.1-38.6) and 45% (n = 36; 95% CI, 33.8-56.5), respectively. Eighteen patients (23%) had SD, 3 patients (4%) had progressive disease, and the status was unable to be determined for 1 patient.

The adverse event (AE) profile was considered acceptable by the researchers and was consistent with previously reported safety data for approved indications of nivolumab. “The majority of events were manageable, with resolution occurring when immune-modulating medications were administered,” said Younes.

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.

AEs resulting in discontinuation included autoimmune hepatitis (n = 1), increased ALT/AST levels (n = 1), and multiorgan failure (n = 1). There 3 deaths, 1 due to progression, 1 due to multiorgan failure due to Epstein-Barr virus—positive T-cell lymphoma, and 1 for which the cause was undetermined after lost follow-up.

In his concluding remarks, Younes noted, “In addition to the recent FDA approval, nivolumab is also under review by the European Medicines Agency for use in previously treated patients with cHL.&rdquo

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).