Combo Regimen Shows Significant Antitumor Activity in Refractory/Relapsed Neuroblastoma

In a study of patients with relapsed or refractory neuroblastoma, combination therapy with irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (GM-CSF) yielded significant antitumor activity (J Clin Oncol. 2020 Apr 28. Epub ahead of print).

“The combination of irinotecan, temozolomide, dintuximab, and [GM-CSF] demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial,” wrote Rajen Mody, MS, MD, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, and colleagues, who assessed the response rate and toxicity of this regimen in an expanded cohort of patients.

Patients were deemed eligible for inclusion in the study at the point of first relapse or designation of refractory disease. Temozolomide and irinotecan were administered on days 1 to 5 of 21-day cycles, dintuximab was administered on days 2 to 5, and GM-CSF was administered on days 6 to 12.

The primary end point of the study was objective response, assessed on an intent-to-treat basis per International Neuroblastoma Response Criteria.

A total of 17 patients were randomized to receive irinotecan, temozolomide, dintuximab, and GM-CSF between February 2013 and March 2015, and 36 additional patients were nonrandomly given the combination regimen between August 2016 and May 2017.

Objective responses, including complete or partial responses, were observed in 9 (52.9%) randomized patients (95% CI, 29.2%-76.7%) and 13 (36.1%) nonrandomized patients (95% CI, 20.4%-51.8%).

Overall, 22 (41.5%) patients had objective responses (95% CI, 28.2%-54.8%), and 22 had stable disease. The 1-year progression-free and overall survival rates were 67.9% ± 6.4% (95% CI, 55.4%-80.5%) and 84.9% ± 4.9% (95% CI, 75.3%-94.6%), respectively.

Because 2 patients were not given protocol therapy, only 51 patients were evaluable for toxicity. Frequently reported grade ≥3 toxicities among these 51 patients were fever/infection (35.3%), neutropenia 33.3%, pain (29.4%), and diarrhea (19.6%). There was 1 patient with unacceptable toxicity (grade 4 hypoxia).

Of note, higher DIN trough levels were linked to response.

In patients with relapsed/refractory neuroblastoma, the combination of irinotecan, temozolomide, dintuximab, and GM-CSF has significant antitumor activity, Dr Mody and colleagues said.

“Study of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers,” they concluded.—Hina M. Porcelli