Neuroblastoma cells microscope image
Credit: OGPhoto/GettyImages

A retrospective study led by University of Chicago researchers has shown that “bridge” therapy between induction and consolidation treatments benefits high-risk neuroblastoma patients who respond poorly to induction.

“There are approximately 700–800 cases of neuroblastoma each year and about half of these cases will be high-risk,” first author Ami Desai, from the Department of pediatrics at the University of Chicago told Inside Precision Medicine.

Patients with neuroblastoma are typically treated first with induction therapy consisting of chemotherapy and surgery followed by consolidation therapy, which involves high-dose chemotherapy plus autologous stem cell transplantation (ASCT).

Despite this intensive, multi-modality approach, “approximately 40% of patients with high-risk neuroblastoma continue to relapse, and survival for this cohort of patients is dismal,” Desai said.

In order to improve outcomes, researchers have suggested that post-induction bridge therapy before consolidation with ASCT could reduce disease burden among patients with residual disease at the end of induction, and many providers are already using this approach.

Treatments include dinutuximab combined with irinotecan and temozolomide (DIT), targeted therapy with radiolabeled meta-iodobenzylguanidine (131I-MIBG), and combinations of chemotherapeutic agents, but the benefits of this strategy are unclear.

To investigate, Desai and colleagues carried out a multicenter, retrospective analysis of data from 201 high-risk neuroblastoma patients who had residual disease after completing induction therapy between 2008 and 2018.

They report in Cancer that the patients were treated according to three strategies which varied according to physician, institutional, or family preferences but were broadly based on response to induction therapy at metastatic sites.

The first group (cohort 1; n=123) underwent consolidation with ASCT directly after the completion of induction therapy, the second group (cohort 2; n=51) received bridge therapy before ASCT, and the third group (cohort 3; n=27) received post-induction therapy but did not undergo ASCT.

The researchers note that the main reason physicians’ gave for not using consolidation therapy in cohort 3 was poor metastatic response to post-induction therapy.

Desai and team found that the overall primary tumor response rate (comprising complete and partial responses) at the end of therapy was significantly better for cohort 1 (97.6%) than cohorts 2 (78.3%) and 3 (81.4%), and a similar pattern was observed for end-induction metastatic soft tissue and bone disease response (85.4 versus 47.1 and 51.8%, respectively).

In spite of this, the 3-year event-free survival (EFS) and overall survival (OS) rates were not significantly different between cohorts 1 and 2, which the researchers say “suggests that patients in cohort 2 may have benefited from the bridge therapy.”

By contrast, individuals in cohort 3 had significantly worse EFS and OS than those in cohorts 1 and 2.

Among patients with stable, but not improved, metastatic disease at the end of induction therapy, 3-year EFS was significantly better in cohort 2 than in cohort 1, which Desai et al believe “further supports the efficacy of bridge treatment.”

“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,” they write.

The researchers also found that four patients in cohort 3 had a complete response at metastatic sites after bridge therapy. These individuals had significantly better 3-year EFS than those with residual metastatic disease.

Commenting on the findings, Desai said: “Response to induction therapy is known to be prognostic of survival, and our study suggests that bridge therapy prior to ASCT benefits high-risk neuroblastoma patients with poor response to induction.”

She added: “Although we also identified a small number of patients with favorable outcome who achieved a metastatic complete response to post-induction therapy who did not undergo ASCT, prospective studies will need to be conducted to confirm these findings.”

Also of Interest