Checkpoint Inhibitor Therapy

The anti–PD-1 antibody nivolumab induced objective responses in 20 of 23 adult patients (87%) with relapsed Hodgkin lymphoma.[29]

In a phase I/II study of children with refractory malignancies, single-agent nivolumab was tolerable and showed antitumor activity.[30][Level of evidence C3]

In a phase I/II study of children with refractory malignancies, single-agent nivolumab was tolerable and showed antitumor activity.[30][Level of evidence C3]

Among ten children with Hodgkin lymphoma, there was one complete response, two partial responses, and five cases of stable disease.

Twenty-eight patients, aged 5 to 30 years, with low-risk relapsed Hodgkin lymphoma were treated with four cycles of nivolumab and brentuximab vedotin. Patients who had a complete metabolic response to this therapy received an additional two cycles of nivolumab and brentuximab vedotin. Patients who had an inadequate response received intensification therapy with two cycles of brentuximab vedotin and bendamustine. Complete metabolic response (Deauville score ≤3) was assessed after the initial four cycles of treatment or after intensification therapy. Those who achieved a complete metabolic response at any time received involved-field radiation therapy after six total cycles of immunotherapy.[31]

Twenty-eight patients, aged 5 to 30 years, with low-risk relapsed Hodgkin lymphoma were treated with four cycles of nivolumab and brentuximab vedotin. Patients who had a complete metabolic response to this therapy received an additional two cycles of nivolumab and brentuximab vedotin. Patients who had an inadequate response received intensification therapy with two cycles of brentuximab vedotin and bendamustine. Complete metabolic response (Deauville score ≤3) was assessed after the initial four cycles of treatment or after intensification therapy. Those who achieved a complete metabolic response at any time received involved-field radiation therapy after six total cycles of immunotherapy.[31]

After four cycles of nivolumab and brentuximab vedotin, 23 of 28 patients (82%) achieved a complete metabolic response.

Twenty-eight patients, aged 5 to 30 years, with low-risk relapsed Hodgkin lymphoma were treated with four cycles of nivolumab and brentuximab vedotin. Patients who had a complete metabolic response to this therapy received an additional two cycles of nivolumab and brentuximab vedotin. Patients who had an inadequate response received intensification therapy with two cycles of brentuximab vedotin and bendamustine. Complete metabolic response (Deauville score ≤3) was assessed after the initial four cycles of treatment or after intensification therapy. Those who achieved a complete metabolic response at any time received involved-field radiation therapy after six total cycles of immunotherapy.[31]

Twenty-six of the 28 patients (93%) achieved a complete metabolic response at some time before radiation therapy.

Twenty-eight patients, aged 5 to 30 years, with low-risk relapsed Hodgkin lymphoma were treated with four cycles of nivolumab and brentuximab vedotin. Patients who had a complete metabolic response to this therapy received an additional two cycles of nivolumab and brentuximab vedotin. Patients who had an inadequate response received intensification therapy with two cycles of brentuximab vedotin and bendamustine. Complete metabolic response (Deauville score ≤3) was assessed after the initial four cycles of treatment or after intensification therapy. Those who achieved a complete metabolic response at any time received involved-field radiation therapy after six total cycles of immunotherapy.[31]

At 31.9 months of follow-up, the 3-year EFS rate was 87%, and the PFS rate was 95%.

Twenty-eight patients, aged 5 to 30 years, with low-risk relapsed Hodgkin lymphoma were treated with four cycles of nivolumab and brentuximab vedotin. Patients who had a complete metabolic response to this therapy received an additional two cycles of nivolumab and brentuximab vedotin. Patients who had an inadequate response received intensification therapy with two cycles of brentuximab vedotin and bendamustine. Complete metabolic response (Deauville score ≤3) was assessed after the initial four cycles of treatment or after intensification therapy. Those who achieved a complete metabolic response at any time received involved-field radiation therapy after six total cycles of immunotherapy.[31]

The safety profile was consistent with that of each agent used.

In a phase II study, pediatric and young adult patients (70% were <18 years) with standard-risk relapsed or refractory Hodgkin lymphoma were treated with nivolumab and brentuximab vedotin.[32]

In a phase II study, pediatric and young adult patients (70% were <18 years) with standard-risk relapsed or refractory Hodgkin lymphoma were treated with nivolumab and brentuximab vedotin.[32]

After four induction cycles of nivolumab plus brentuximab vedotin, 59% of patients (23 of 43) achieved a complete metabolic response.

In a phase II study, pediatric and young adult patients (70% were <18 years) with standard-risk relapsed or refractory Hodgkin lymphoma were treated with nivolumab and brentuximab vedotin.[32]

Patients without a complete metabolic response also received intensification therapy with brentuximab vedotin and bendamustine before undergoing autologous HSCT. After intensification therapy and before consolidation therapy, 94% of patients achieved a complete metabolic response.

The anti–PD-1 antibody pembrolizumab produced an objective response rate of 65% in 31 heavily pretreated adult patients with Hodgkin lymphoma whose disease relapsed after receiving brentuximab vedotin.[34] For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.

A phase II study of 210 adult patients (median age, 35 years; range, 18–76 years) with refractory/relapsed classical Hodgkin lymphoma who were treated with pembrolizumab reported the following:[35][Level of evidence C3]

A phase II study of 210 adult patients (median age, 35 years; range, 18–76 years) with refractory/relapsed classical Hodgkin lymphoma who were treated with pembrolizumab reported the following:[35][Level of evidence C3]

An overall response rate of 69% (95% CI, 62.3%–75.2%), with a complete response rate of 22.4% (95% CI, 6.9%–28.6%).

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

Two patients achieved complete responses, and seven patients achieved partial responses, for an overall objective response rate of 60% (95% CI, 32.2%–83.7%).

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

Adverse events were documented in 97% of the 154 patients enrolled in the study; most were grades 1 to 2 toxicities.

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

Grades 3 to 5 events, seen in 45% of the cases, consisted mostly of anemia and lymphopenia.

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

Treatment interruptions were most commonly caused by transaminitis, hypertension, pleural effusion, and pneumonitis.

In a multicenter, nonrandomized, open-label, single-arm phase I/II study, 15 pediatric patients with relapsed or refractory Hodgkin lymphoma were treated with pembrolizumab at a dose of 2 mg/kg every 3 weeks.[36][Level of evidence C1]

Two deaths were attributed to drug administration (one resulting from pulmonary edema and the other from pleural effusion and pneumonitis).