Programmed death-1 (PD-1) inhibitors can play an important role in the treatment of relapsed/refractory classical Hodgkin lymphoma (HL) patients in “real-world” settings.

“In HL patients who progress after prior cytotoxic therapy, immunotherapy in a real-world setting induces outcomes that are similar to in prior clinical trials,” Steven M. Bair, MD, of the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, told MedPage Today. “For those who do progress, our study shows they can respond to conventional strategies, which could provide a bridge to transplant.”

Approximately 8,260 patients are diagnosed with HL in the United States each year, according to statistics from the Leukemia & Lymphoma Society. While HL is a highly curable malignancy, 20% of patients are not able to be cured with conventional treatments. PD-1 inhibition has resulted in impressive activity in the relapsed/refractory setting, leading to FDA approval of nivolumab in 2016 and pembrolizumab in 2017, but there has been limited information on experience with these agents in HL patients outside of clinical trials.

At the American Society of Hematology (ASH) annual meeting, Bair presented a multicenter, retrospective analysis of relapsed/refractory HL patients treated with PD-1 inhibitors in a real-world setting. The study included 42 patients, median age of 34, from seven centers in the United States. At diagnosis, 60% of the patients had stage III/IV disease, half had previously undergone an autologous stem cell transplant (SCT), and 7% had prior allogeneic SCT.

Patients received a median of four lines of therapy prior to the PD-1 inhibitor; 85% had ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/AVD as frontline therapy, and 95% had brentuximab vendotin. Nivolumab was the initial PD-1 inhibitor; three-quarters of patients received a dose of 3 mg/kg every 2 weeks. Concurrent therapies with PD-1 inhibitors were used at some point in 19% of patients.

Almost two-thirds of patients (62%) achieved an overall response to nivolumab as assessed by the treating physician, with 45% achieving a complete response (CR). The median time to best response was 3 months.

At a median follow-up of 13 months at the time of the analysis, the median progression-free survival (PFS) and overall survival (OS) had not been reached. The 12-month OS rate was 96%, and the 12-month PFS rate was 65%. The median duration of therapy was 9 months. The median duration of response in patients with CR was 13 months, and for those in partial response, 9 months.

Dose delays occurred in one-third of patients — most commonly due to toxicity, non-adherence, and patient preference, Bair reported. Dose delays did not affect PFS: Half the patients discontinued the original PD-1 inhibitor, primarily due to disease progression. Four patients died — all due to disease progression.

Among the 40 patients for whom toxicity data were available, nearly half had toxicity attributed to the PD-1 inhibitor. The most common toxicities were hypothyroidism, rash, pneumonitis/dyspnea, and colitis. Toxicities resulting in drug discontinuation included encephalitis, colitis, and skin graft-versus-host disease. Toxicities were managed with systemic steroids, thyroid replacement, drug discontinuation, dose delay, or local steroid therapy. There were no treatment-related deaths.

In the 21 patients who discontinued PD-1 inhibitor therapy, two-thirds had subsequent systemic therapies and 12 were evaluable for response. A clinical benefit of systemic therapy was seen immediately after PD-1 inhibitor therapy in 75% of patients, with five responding to cytotoxic chemotherapies.

“Patients can respond after failing initial therapy,” Bair said. “The thought is that checkpoint inhibitors sensitize tumors to cytotoxic therapy.”

In another presentation at ASH17, French researchers hypothesized that anti-PD-1 therapy may increase sensitivity to chemotherapy given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). The retrospective analysis of 30 relapsed/refractory HL patients showed that patients with an unsatisfactory response or progressive disease with anti-PD-1 therapy had a new objective response with chemotherapy alone (61%) or chemotherapy in combination with anti-PD-1 therapy (90%). This response could make some patients eligible for allograft, the researchers suggested.

“This is the first multi-center retrospective analysis to describe the real-world experience with PD-1 inhibitors in HL patients in the United States. There was good concordance in a real-world setting with clinical trials in terms of overall response rate, survival, and the toxicity profile in general,” Bair said, noting that the patterns of discontinuation and dose delays did not affect outcomes.

“Systemic therapies after PD-1 inhibitor discontinuation appear to be active. Our results support the important role of PD-1 inhibitor therapy in relapsed/refractory HL and provide insight into practice patterns,” he continued. “When HL patients fail cytotoxic therapy, they have an option of salvage immunotherapy.”

Researchers are now exploring further regimens, sequences, and combinations with immunotherapy and cytotoxic therapy that could be a bridge to transplant, Bair noted. “We have a possible paradigm to treat HL that is progressing rapidly, and are also starting to see immunotherapy move into the frontline setting in HL.”