‘Bridge’ Therapy May Benefit Some Kids With High-Risk Neuroblastoma

‘Bridge’ Therapy May Benefit Some Kids With High-Risk Neuroblastoma

June 22, 2022 0 By Jennifer Walker

Bridge therapy ahead of autologous stem cell transplantation (ASCT) consolidation may benefit certain high-risk neuroblastoma patients with residual disease following induction regimens, according to a multicenter retrospective study.

In the analysis of more than 200 children with high-risk neuroblastoma, end-of-induction (EOI) response tended to be worse for those who went on to receive bridge therapy prior to ASCT compared with those who went directly to transplant, reported Ami Desai, MD, of the University of Chicago, and colleagues.

Yet at 3 years, no significant differences were observed for event-free survival (EFS, P=0.77) or overall survival (OS, P=0.85) between patients who received bridge therapy and those who went directly to ASCT following induction, they wrote in Cancer.

“Response to induction therapy is known to be prognostic of survival, and our study suggests that bridge therapy prior to consolidation therapy benefits patients with high-risk neuroblastoma with a poor response to induction,” Desai said in a statement. “Also, response to bridge therapy prior to consolidation therapy is associated with outcome, and patients with less than a partial response may benefit from alternative treatment approaches.”

For patients with stable metastatic disease following induction therapy, EFS was significantly improved among the patients who received bridge therapy (P=0.04). “Although no difference in OS was observed, this may reflect the effects of additional treatments that these patients may have received to treat relapsed disease,” noted Desai and coauthors.

Bridge therapies in the study consisted most commonly of chemoimmunotherapy with dinutuximab (Unituxin) plus irinotecan and temozolomide (Temodar; DIT) or 131I-metaiodobenzylguanidine (MIBG). And 3-year EFS and OS rates, respectively, were the following with bridge therapy regimens containing:

  • DIT without MIBG (n=22): 52.7% and 87.3%
  • MIBG without DIT (n=20): 50% and 85%
  • MIBG and DIT (n=2): 100% and 100%
  • No MIBG or DIT (n=7): 57.1% and 85.7%

By comparison, in children that went directly to transplant, 3-year rates were 58.9% for EFS and 80.2% for OS.

“Prospective clinical trials will be needed to validate these findings and identify those patients most likely to benefit from bridge therapy,” Desai’s group concluded.

In an accompanying editorial, Sara Federico, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and Thomas Cash, MD, of Emory University in Atlanta, highlighted how patients who were able to achieve a metastatic complete response (CR) had improved outcomes in comparison to those with EOI metastatic stable disease who did not receive bridge therapy, suggesting “that a subset of patients may benefit from additional therapy before ASCT with the goal of achieving an improved metastatic response before consolidation.”

But while they called the findings “compelling,” the editorialists cautioned against continuing to treat until a metastatic CR without additional prospective studies to validate such an approach.

“The Desai dataset included very few patients (7%) with EOI stable disease, so it is not clear that the ‘metastatic CR bar’ can be applied to all patients with an EOI response worse than a [partial response],” Federico and Cash argued. “This approach may delay consolidation and/or could lead to overtreatment and increased toxicity without additional improvements in outcomes.”

The study consisted of 201 children with high-risk neuroblastoma treated from 2008 to 2018 at six U.S. centers. Desai’s group homed in on those who had a partial response or worse following induction therapy. Of these, 123 underwent consolidation with ASCT following induction (cohort 1), 51 received bridge therapy prior to ASCT (cohort 2), and 27 patients received post-induction therapy but did not undergo ASCT (cohort 3) due to poor metastatic response to post-induction therapy.

Patients in cohort 3 had significantly worse EFS and OS compared with the other two cohorts.

Treatment varied widely among cohorts and was largely based on response at metastatic sites, the study authors noted. Cohort 1 had the highest proportion of patients with a better overall response, and with a metastatic response. For example, only 3.2% of this group had EOI metastatic stable disease in the soft tissue and bone, as compared to 48-51% of those in the other two cohorts. And 7% in cohort 1 had metastatic stable disease in the bone at EOI versus 33.3% in cohort 2 and 18.5% in cohort 3.

While all kids in the study were high risk, a higher proportion of patients in cohorts 2 and 3 were 18 months or older and had stage 4 disease on the International Neuroblastoma Staging System. MYCN amplification was more common among the patients in cohort 1, however.

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    Ian Ingram is Managing Editor at MedPage Today and helps cover oncology for the site.

Disclosures

The study was funded in part by the Matthew Bittker Foundation, the MacRitchie Family, and the NCI.

Desai reported relationships with GlaxoSmithKline, Merck, Ology Medical Education, Pfizer, Viatris, and Y-mAbs Therapeutics. Coauthors disclosed relationships with Alkermes, Fennec Pharmaceuticals, Innervate Radiopharmaceuticals, Lilly, Merck, Novartis, Ology Medical Education, Pfizer, PlatformQ, and Y-mAbs Therapeutics.

Federico reported no disclosures. Cash disclosed relationships with Celgene/Bristol Myers Squibb, EUSA Pharma, Lilly, Roche/Genentech, United Therapeutics, and Y-mAbs Therapeutics.