Late Effects Comparison between Two Chemotherapy Regimens for Hodgkin Lymphoma

Introduction: Hodgkin lymphoma (HL) is highly curable disease, but therapy-related late effects remain a challenge. Risk-adoptive chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) has been a first line treatment option for many years, especially for young adult patients with HL. ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) treatment regimen was designed with the goal of enhancing tumor cytotoxicity to achieve excellent treatment efficacy while limiting long-term toxicity. Response-based chemotherapy with ABVE-PC is a standard treatment approach for pediatric HL. There has been no direct comparison of these regimens, and it remains unknown if chemotherapy with ABVE-PC is superior to ABVD in decreasing long-term side effects.

Methods: We performed a retrospective chart review of pediatric, adolescent, and young adult patients (age 0-39 at diagnosis) treated for HL at University of Nebraska Medical Center and Children's Hospital and Medical Center between 1/1/2006 and 12/31/2021. We recorded demographic data, treatment received, relapse and development of late effects. Patients who received chemotherapy regimens other than ABVE-PC or ABVD were excluded.

Our primary outcome was to compare the need for radiation treatment between the two regimens, as radiation is known to significantly increase the risk of multiple late effects. Our secondary outcome was to compare incidence of several late effects, including cardiotoxicity, secondary malignancy, thyroid dysfunction, and fertility concerns. Descriptive statistics were used to summarize demographic and clinical characteristics of the patients. Chi-Square or Fisher's Exact test was used, as appropriate, to compare all categorical variables between treatment groups. All analyses were conducted in SAS version 9.4.

Results: Out of 105 patients diagnosed with HL, 79 received either ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine in n=24 and doxorubicin, brentuximab, vinblastine, dacarbazine in n=6) or ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide in n=48 and doxorubicin, brentuximab, vincristine, etoposide, prednisone, cyclophosphamide in n=1). As expected, there was a significant difference (p<0.0001) in the age at diagnosis between treatment groups. Those treated with ABVD had a median age of 25.5 compared to 15 in the ABVE-PC group. There was also a significant difference in ethnicity between treatment groups (p=0.04); 20% of those in the ABVE-PC group were Hispanic compared to 3% in the ABVD group. Notably there was no difference in disease risk assignment between treatment groups (Table 1).

There was a significant difference (p=0.005) in the need for post-chemotherapy radiation between treatment groups. Over half of the patients (59%) in the ABVE-PC group required radiation for treatment compared to only 27% in the ABVD group. This was not affected by disease risk assignment (p = 0.63). Cumulative doxorubicin dose also significantly differed between groups (p<0.0001). About 8% of patients treated with ABVE-PC received a cumulative doxorubicin dose of >/=250 mg/m2 compared to 73% of those treated with ABVD (Table 1).

We did not find any statistical differences in the observed late effects between these groups. Relapse was seen in 13% of those treated with ABVD versus 8% of those treated with ABVE-PC (p=0.47) and secondary malignancy was seen in approximately 4% of the patients in each treatment group. Major cardiovascular events occurred in 6% of patients treated with ABVE-PC versus 0% of patients treated with ABVD (p=0.29). Thyroid dysfunction was seen in 19% of patients treated with ABVE-PC and 7% of patients treated with ABVD (p=0.2). Finally, fertility concerns were documented in 50% of patients treated with ABVD versus 39% of patients treated with ABVE-PC (p=0.34) (Table 2).

Conclusion: In our pediatric, adolescent, and young adult HL patients ABVD was superior to ABVE-PC in eliminating the need for radiation, which may have a beneficial impact in decreasing late effects of treatment. Despite a lower cumulative dose of doxorubin in the ABVE-PC treatment group there was a non-statistically significant observed increase in cardiotoxicity, which may be related to the higher rate of radiation. These findings need to be confirmed in a larger, ideally prospective, study.

Raulji:Sanofi-Genzyme: Consultancy.