Meeting News

Triplet therapy shows promise in relapsed, refractory Hodgkin lymphoma

Catherine M. Diefenbach, MD
Catherine M. Diefenbach

SAN DIEGO — Treatment with brentuximab vedotin, nivolumab and ipilimumab appeared well tolerated and showed promising complete response rates in patients with recurrent Hodgkin lymphoma, according to a multicenter phase 1/phase 2 study presented at ASH Annual Meeting and Exposition.

However, the triplet therapy was associated with more grade 3 adverse events than doublet therapy with brentuximab vedotin (Adcetris, Seattle Genetics) and nivolumab (Opdivo, Bristol-Myers Squibb) observed in other study groups.

“In this triplet combination, we found was that, in general, patients did very well and did not have substantial toxicity,” study author Catherine M. Diefenbach, MD, assistant professor at NYU Langone and clinical director of lymphoma program services at Perlmutter Cancer Center, told HemOnc Today. “Most patients tolerated the therapy very well. There were a few patients who had toxicity, most of which was manageable. They were able to stay on study.”

In this ongoing ECOG/ACRIN Cancer Research Group-sponsored study, researchers evaluated 22 patients (median age, 35 years; range, 19-60; 11 men) with confirmed relapsed/refractory Hodgkin lymphoma.

The current analysis includes three groups of patients receiving triplet therapy with:

3 mg/kg IV nivolumab on day 1 of cycles 1-46; 1 mg/kg IV ipilimumab (Yervoy, Bristol-Myers Squibb) on day 1 every 12 weeks for 2 years; and 1.2 mg/kg IV brentuximab vedotin on day 1 of cycles 1-16 (group G; n = 7);

3 mg/kg IV nivolumab, 1 mg/kg IV ipilimumab and 1.8 mg/kg IV brentuximab vedotin (group H; n = 6); or

3 mg/kg nivolumab; 1 mg/kg ipilimumab and 1.2 mg/kg brentuximab vedotin (expansion cohort, group I; n = 9).

Patients received a median of two (range, 1-5) prior treatments — including one patient previously treated with brentuximab vedotin — and nine patients (41%) previously underwent hematopoietic stem cell transplantation.

Researchers evaluated dose-limiting toxicity within the first treatment cycle.

Of the 22 enrolled patients, three dose-limiting toxicities occurred, one in each group.

One patient in group G discontinued treatment after cycle 1 due to grade 4 diabetic ketoacidosis and hyperglycemia.

One patient in group H experienced transient grade 3 aspartate aminotransferase elevation, although it did not cause a therapy delay.

One patient in group I, who had undergone allogeneic HSCT, had grade 4 Stevens-Johnson syndrome with grade 3 pruritis, rash and graft-versus-host disease. This patient’s treatment was discontinued.

Grade 3 adverse events that led to dose delays included rash, colitis, gastritis, pancreatitis and arthritis, each occurring in one patient. Grade 2 angioedema occurred in one patient in cycle 1, leading to discontinuation. There were no grade 5 adverse events.
A total of 19 patients were evaluable for response, after excluding three patients who stopped treatment after cycle 1.

The overall response rate for the full population was 82% (n = 18) with 72% (n = 16) achieving complete response. Among the patients evaluable for response after at least three treatment cycles, the ORR was 95% (n = 18), with 84% (n = 16) achieving complete response.

Six patients proceeded to HSCT from treatment.

The median PFS had not been reached at a median follow-up of 0.75 years, and median OS had not been reached at a median follow-up of 0.99 years.
A larger, phase 2 study is underway that compares patients randomly assigned to treatment with either doublets or triplets, according to Diefenbach.
“This is obviously too small a study to be practice-changing,” Diefenbach told HemOnc Today. “However, it's very exciting data, and it's led to a large, randomized phase 2 study comparing the doublet regimen of brentuximab vedotin and nivolumab with the triplet regimen of the dual immunotherapy and brentuximab vedotin.” – by Jennifer Byrne

Reference:

Diefenbach C, et al. Abstract 679. Presented at: ASH Annual Meeting and Exposition; Dec 1-4, 2018; San Diego.

Disclosures : Diefenbach reports research funding from or consultant roles with Acerta, Bristol-Myers Squibb, Denovo, Genentech, Incyte, Merck, Millennium/Takeda, Seattle Genetics and Trillium. Please see the abstract for all other authors’ relevant financial disclosures.

Catherine M. Diefenbach, MD
Catherine M. Diefenbach

SAN DIEGO — Treatment with brentuximab vedotin, nivolumab and ipilimumab appeared well tolerated and showed promising complete response rates in patients with recurrent Hodgkin lymphoma, according to a multicenter phase 1/phase 2 study presented at ASH Annual Meeting and Exposition.

However, the triplet therapy was associated with more grade 3 adverse events than doublet therapy with brentuximab vedotin (Adcetris, Seattle Genetics) and nivolumab (Opdivo, Bristol-Myers Squibb) observed in other study groups.

“In this triplet combination, we found was that, in general, patients did very well and did not have substantial toxicity,” study author Catherine M. Diefenbach, MD, assistant professor at NYU Langone and clinical director of lymphoma program services at Perlmutter Cancer Center, told HemOnc Today. “Most patients tolerated the therapy very well. There were a few patients who had toxicity, most of which was manageable. They were able to stay on study.”

In this ongoing ECOG/ACRIN Cancer Research Group-sponsored study, researchers evaluated 22 patients (median age, 35 years; range, 19-60; 11 men) with confirmed relapsed/refractory Hodgkin lymphoma.

The current analysis includes three groups of patients receiving triplet therapy with:

3 mg/kg IV nivolumab on day 1 of cycles 1-46; 1 mg/kg IV ipilimumab (Yervoy, Bristol-Myers Squibb) on day 1 every 12 weeks for 2 years; and 1.2 mg/kg IV brentuximab vedotin on day 1 of cycles 1-16 (group G; n = 7);

3 mg/kg IV nivolumab, 1 mg/kg IV ipilimumab and 1.8 mg/kg IV brentuximab vedotin (group H; n = 6); or

3 mg/kg nivolumab; 1 mg/kg ipilimumab and 1.2 mg/kg brentuximab vedotin (expansion cohort, group I; n = 9).

Patients received a median of two (range, 1-5) prior treatments — including one patient previously treated with brentuximab vedotin — and nine patients (41%) previously underwent hematopoietic stem cell transplantation.

Researchers evaluated dose-limiting toxicity within the first treatment cycle.

Of the 22 enrolled patients, three dose-limiting toxicities occurred, one in each group.

One patient in group G discontinued treatment after cycle 1 due to grade 4 diabetic ketoacidosis and hyperglycemia.

One patient in group H experienced transient grade 3 aspartate aminotransferase elevation, although it did not cause a therapy delay.

One patient in group I, who had undergone allogeneic HSCT, had grade 4 Stevens-Johnson syndrome with grade 3 pruritis, rash and graft-versus-host disease. This patient’s treatment was discontinued.

Grade 3 adverse events that led to dose delays included rash, colitis, gastritis, pancreatitis and arthritis, each occurring in one patient. Grade 2 angioedema occurred in one patient in cycle 1, leading to discontinuation. There were no grade 5 adverse events.
A total of 19 patients were evaluable for response, after excluding three patients who stopped treatment after cycle 1.

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The overall response rate for the full population was 82% (n = 18) with 72% (n = 16) achieving complete response. Among the patients evaluable for response after at least three treatment cycles, the ORR was 95% (n = 18), with 84% (n = 16) achieving complete response.

Six patients proceeded to HSCT from treatment.

The median PFS had not been reached at a median follow-up of 0.75 years, and median OS had not been reached at a median follow-up of 0.99 years.
A larger, phase 2 study is underway that compares patients randomly assigned to treatment with either doublets or triplets, according to Diefenbach.
“This is obviously too small a study to be practice-changing,” Diefenbach told HemOnc Today. “However, it's very exciting data, and it's led to a large, randomized phase 2 study comparing the doublet regimen of brentuximab vedotin and nivolumab with the triplet regimen of the dual immunotherapy and brentuximab vedotin.” – by Jennifer Byrne

Reference:

Diefenbach C, et al. Abstract 679. Presented at: ASH Annual Meeting and Exposition; Dec 1-4, 2018; San Diego.

Disclosures : Diefenbach reports research funding from or consultant roles with Acerta, Bristol-Myers Squibb, Denovo, Genentech, Incyte, Merck, Millennium/Takeda, Seattle Genetics and Trillium. Please see the abstract for all other authors’ relevant financial disclosures.

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