Response-Based Radiation Is Effective, Safe in Pediatric High-Risk Hodgkin Lymphoma

The use of response-based consolidation coupled with radiation therapy was found to be effective and well tolerated, with low failure rates, in pediatric patients with high-risk classical Hodgkin lymphoma, according to results of a phase 3 trial that were presented at the 2020 ASTRO Annual Meeting.^1,2

The study, which was conducted by the Children’s Oncology Group, included 164 patients who were younger than 22 years old and had either stage IIIB (43%) or stage IVB (57%) disease. Patients were defined as rapid early responders or slow early responders after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC).

Slow early responders received 2 additional chemotherapy cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC, followed by adapted involved-field radiation therapy to areas of bulky disease and/or slow-responding sites. The rapid early responders received 2 additional ABVE-PC cycles and involved-site radiation to areas of initial bulky involvement.

At a median follow-up of 4.5 years, 27 of 145 patients had relapsed while 23 patients were evaluable; 11 of them were rapid early responders and 12 were slow early responders. Of the relapses, 64% occurred in an initial involvement site, including 18% that were at an initial site of bulky disease, 32% in a new site of disease that would not been covered by RT, and 2.4% were isolated out-of-field relapses that would have been covered by IFRT. Ninety-four percent of relapses occurred in sites that were initially PET2-negative.

“We have determined response-based consolidation with modern radiation therapy appears to be a safe and effective standard of care with very low rates of failures and will continue to be the backbone of the standard protocol for pediatric patients with high-risk Hodgkin lymphoma,” said lead study author Rahul R. Parikh, MD, of the Rutgers Cancer Institute of New Jersey.

In an interview with OncLive, Parikh, medical director of the Laurie Proton Therapy Center, and a radiation oncologist at Rutgers Cancer Institute of New Jersey, dove into the details of this response-based approach in Hodgkin lymphoma and what it means for clinical practice going forward.

OncLive: What was the rationale to conduct this type of trial? What are the unmet needs of this patient population?

Parikh: For high-risk pediatric Hodgkin lymphoma patients, the usual treatment has been combined modality therapy—induction chemotherapy, followed by radiation therapy. This study, [which is] part of a phase 3 study from the Children’s Oncology Group, was designed to determine whether response-adapted therapy improves outcomes in high-risk pediatric classical Hodgkin lymphoma. We examined patterns of relapse in the study, which utilized a modern, response-adapted radiation therapy protocol.

What was unique about the study design?

The design of this trial allowed for a response-adapted radiation therapy program after induction chemotherapy. This meant that patients who had large [bulky] disease or a “slow response” after chemotherapy based on functional PET/CT imaging, went on to have radiation therapy fields that were designed to maximally control their disease.

Please discuss the findings in detail. What did you find most intriguing about them?

For a 25-month period from 2009 to 2012, the study looked at 164 evaluable patients younger than 22 years old with stage 3b [43%] and stage 4b [57%] classical Hodgkin lymphoma. Overall, 84% of patients presented with large tumors, or bulky disease. Patients were categorized as rapid early responders or slow early responders after receiving 2 cycles of a standard chemotherapy combination used with radiation therapy. The slow early responder patients were randomized to receive 2 additional standard combination cycles as well as 2 chemotherapy cycles of ifosfamide and vinorelbine, followed by the delivery of radiation adapted only to larger tumors or slow-responding sites.

At the 4.5-year median follow-up, 27 of 145 patients [19%] relapsed and 23 patients were evaluable. Among these 23 patients, 11 were rapid early responders and 12 were slow early responders. Within the 23 evaluable patients with relapse, there were a total of 105 total sites [median = 4, range: 1-11] of relapse. Sixty-four percent of relapses occurred within an initial site of involvement. Overall, 94% of relapses occurred in sites that were initially PET2-negative. Researchers have determined [that] response-based consolidation with modern radiation therapy appears to be a safe and effective standard of care with very low rates of failures.

Were there any safety differences between the slow and rapid responders?

There did not appear to be any differences in safety between these groups of patients.

What are the next steps of this study?

Future/current studies will further examine the role of immunotherapy and targeted agents in combination with standard chemotherapy options and add radiotherapy for those patients with more resistant disease.

References

1. Parikh RR, Hoppe BS, Hodgson D, et al. Patterns of relapse from a phase 3 study of response-based therapy for high-risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group. Presented at: 2020 ASTRO Annual Meeting; October 24-28, 2020; virtual. Abstract 73.
2. Studying patterns of relapse in pediatric Hodgkin lymphoma using a response-based therapy approach. News release. Rutgers Cancer Institute of New Jersey. October 23, 2020. November 30, 2020. https://bit.ly/3oamk9w