SUMMARY: The American Cancer Society estimates that in the United States for 2023, about 8830 new cases of Hodgkin Lymphoma will be diagnosed and about 900 patients will die of the disease. Hodgkin Lymphoma is classified into two main groups – Classical Hodgkin Lymphomas and Nodular Lymphocyte Predominant type, by the World Health Organization. The Classical Hodgkin Lymphomas include Nodular sclerosing, Mixed cellularity, Lymphocyte rich, Lymphocyte depleted, subtypes and accounts for approximately 10% of all malignant lymphomas. Nodular sclerosis Hodgkin lymphoma histology, accounts for approximately 80% of Hodgkin Lymphoma cases in older children and adolescents in the United States. Classical Hodgkin Lymphoma is a malignancy of primarily B lymphocytes and is characterized by the presence of large mononucleated Hodgkin and giant multinucleated Reed-Sternberg (RS) cells collectively known as Hodgkin and Reed-Sternberg cells (HRS).
Patients with Stage I/II classical Hodgkin Lymphoma (cHL) with bulky disease (mass more than 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray), are typically treated with chemotherapy followed by radiation. However radiotherapy to the chest can result in late complications which include risk of secondary malignancies, particularly breast cancer in women treated under the age of 30 years, cardiovascular disease, as well as the possibility of radiation-associated pneumonitis and fibrosis. Given the prognostic impact of interim PET scans after two cycles of chemotherapy (PET2) on Progression Free Survival, several trials evaluated response-adapted therapy, with de-escalation of treatment in patients with negative PET2, and intensifying therapy in patients with PET2-positive findings.
CALGB 50801 is a single-arm, Phase II trial with response-adapted therapy on the basis of centrally reviewed interim PET, and is the first study focusing exclusively on patients with bulky Stage I and II disease. The researchers hypothesized that a PET-adapted strategy would be effective and limit the use of mediastinal radiotherapy and prevent late complications in this high-risk group of patients. This study included 94 eligible and evaluable patients with bulky disease, for the safety and efficacy analyses. Patients were treated with two cycles of full-dose ABVD (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine) without delay, regardless of neutrophil count, followed by interim FDG PET (PET2). Patients with a negative PET2 defined as 1-3 on the Deauville 5 point scale received four additional cycles of ABVD. Patients with a positive interim PET2 defined as 4 and 5 on the Deauville 5 point scale were treated with escalated BEACOPP (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone) for four cycles, followed by 30 Gy involved-field radiotherapy. Median age of patients was 30 years, 22% were PET2 positive and 78% were PET2 negative after two cycles of ABVD.
The Primary objectives of this study were to use a PET-adapted approach to maintain Progression Free Survival (PFS) in patients with negative PET2 without the use of radiotherapy, and to improve outcomes in PET2 positive patients by intensifying therapy. The researchers assessed whether PFS for PET2 positive patients receiving escalated BEACOPP was not inferior to that of PET2 negative patients receiving ABVD, compared with historical differences in PFS between PET2 positive patients and PET2 negative patients receiving ABVD.
This PET-adapted study met the primary objective of maintaining ongoing remissions in PET2 negative patients treated with chemotherapy only, without the addition of radiation therapy. The Primary end point of 3-year Progression Free Survival was 93.1% in PET2 negative patients and 89.7% in PET2 positive patients. The 3 year Overall Survival was 98.6% and 94.4%, respectively. Outcomes were similar with intensified chemotherapy followed by radiation for the 22% of PET2 positive patients. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia. The majority of PET2 positive patients remained disease free without the need for high-dose chemotherapy with Autologous Stem Cell Transplant. The researchers pointed out that this study was initiated before the publication of RATHL study, and consistent with current practice, recommended eliminating Bleomycin from cycles 3-6 in PET2 negative patients.
It was concluded from this study that PET-adapted therapy in bulky Stage I/II classical Hodgkin Lymphoma met its primary goal and was associated with an excellent 3-year Progression Free Survival in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.
Positron Emission Tomography–Adapted Therapy in Bulky Stage I/II Classic Hodgkin Lymphoma: CALGB 50801 (Alliance). LaCasce AS, Dockter T, Ruppert AS, et al. J Clin Oncol 2023; 41:1023-1034.
