A recent analysis confirmed the importance of radiotherapy (RT) in pediatric patients with early‐stage low-risk classical Hodgkin lymphoma (cHL) who had a positive interim PET response after 1 cycle (PET1) of treatment with doxorubicin, vincristine, prednisone, and cyclophosphamide (AVPC), according to researchers.

The sites of relapse in these patients suggest the need to further optimize therapy with alternative upfront systemic therapy or intensified RT at the relapse sites, the researchers wrote in the journal Blood.

The researchers explained that the Children’s Oncology Group AHOD0431 trial examined whether reducing upfront treatment in early-stage, low‐risk cHL by using a response‐based approach with minimal initial chemotherapy and omission of involved‐field RT (IFRT) in patients with a complete response (CR) could maintain overall survival and event‐free survival (EFS) while reducing late toxicity. Results showed that a slow early response (SER) at PET1 was associated with significantly worse EFS in the absence of IFRT despite patients having a CR at the end of chemotherapy.


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In the present analysis, the researchers assessed the impact of PET1 and IFRT on outcomes and relapse pattern in patients on AHOD 0431 who underwent PET1 response assessment after AVPC (ClinicalTrials.gov Identifier: NCT00302003).

The researchers defined rapid early response (RER) as a negative PET1 and SER as a positive PET1. Patients with a partial response (PR) by CT and functional imaging following 3 chemotherapy cycles received 21 Gy IFRT, while patients with CR received no IFRT.

The researchers evaluated progression-free survival (PFS) for the patients with RER and SER treated with or without IFRT. The team also assessed recurrence sites (initial, new, or both) and characterized relapses involving initial sites as those “within PET1+ site” or “initially involved but outside PET1+ site.”

A total of 222 patients who underwent PET1 assessment and, if positive, a subsequent PET3 assessment were included in the current analysis. The median follow-up was 118 months. The PET1 response assessment indicated 54% of patients had RER and 46% had SER.

Relapse occurred in 18% of patients. Both patients with and without relapse had a median age of 15 years. The median time to relapse was 10.02 (range, 4.11‐32.39) months. For patients with RER, the median time to relapse was 10.83 months in those who did not receive RT and 6.57 months in those who received RT. For patients with SER, the median time to relapse was 8.46 months in those who did not receive RT and 21.40 months in those who received RT.

Patients with SER were more likely to be female (P =.032), have stage II disease (P =.0017), have an erythrocyte sedimentation rate >20 (P =.0001), and have 3 or more sites of disease (P =.0052).

The 10-year PFS rate among patients with RER was 96.6% with IFRT and 84.1% without IFRT (P =.10). Among those with SER, the 1-year PFS rate was 80.9% with IFRT and 64.0% without IFRT (P =.03).

A total of 14 relapses occurred in 90 patients with RER who did not receive IFRT, and all of these relapses included an initial site. A total of 16 relapses occurred in 45 patients with SER who received no IFRT, and 14 of the 16 (88%) relapses were in the initial site (9 PET1+ site only). A total of 10 relapses occurred in 58 patients with SER who received IFRT, and 5 of the 10 (50%) relapses were in the PET1+ site.

“Following 3 cycles of AVPC alone, patients [with RER] experienced favorable results,” the researchers wrote. “Conversely, patients [with SER] experienced unfavorable outcomes with AVPC alone, although they improved with 21‐Gy IFRT. Radiotherapy remains an important component of treatment for patients who [have SER].”

Limitations of the study included the exploratory nature, which did not reflect specific upfront planned endpoints, and the small sample size in some subgroups.

Reference

Parekh A, Keller FG, McCarten KM, et al. Targeted radiotherapy for early-stage low-risk pediatric Hodgkin lymphoma slow early responders: a COG AHOD0431 analysis. Published online June 28, 2022.  Blood. doi:10.1182/blood.2022016098

This article originally appeared on Hematology Advisor