Risk-Oriented Therapy in Adults Previously Untreated Hodgkin’s Lymphoma (HL) with ABVD Followed by Involved Field Radiotherapy (IFRT). Final Results of the Argentinian Group for Treatment of Acute Leukemia (GATLA) Phase III Study.
Authors: Pavlovsky Santiago , Corrado Claudia S. , Pavlovsky Miguel A. , Prates Virginia , Zoppegno Lucia , Giunta Mario , Cerutti Ider , Palomino Elsa , Pagani Fernando , Lastiri Francisco , Narbaitz Maria C. , Cavagnaro Fernando , Avila Graciela 
Published: October 2019

Abstract
Introduction: The present goal standard for the treatment of HL is ABVD plus low doses of IFRT. With the purpose of maintaining a high response rate, event-free survival (EFS) and overall survival (OSV) with minimal toxicity we adapted the number of cycles of ABVD and doses of IFRT to the risk at diagnosis and early response.
Methods: From December 1996, up to October 2005 a total of 527 patients, 15 to 75 years old (median 28) previously untreated entered the study. Patients with clinical stage I, II, IIIA without bulky tumor (< 10 cm mass or < 1/3 thoraxic diameter) (low-risk) received 3 cycles of ABVD followed by IFRT 25 Gy to all node areas of more than 2 cm at diagnosis. A total of 55 out of 267 patients (21%) with low-risk who failed to achieve complete remission (CR) after 3 cycles of ABVD were included as high-risk completing 6 cycles of ABVD. Patients with clinical stage IIIB and IV or all other stages with bulky disease or persistance lymph nodes areas after 3rd cycle of ABVD (high risk) received 6 cycles of ABVD followed by IFRT 30 Gy to bulky areas at diagnosis or those areas remaining > 2cm after 3 cycles. The dose of ABVD was the standard; Adriamycin 25 mg/m2, Bleomycin 10 IU/m2, Vinblastine 6 mg/m2 and Dacarbacine 375 mg/m2 all IV on day 1 and 15 of each 28 days cycles. Patients who achieved partial remission (PR) were salvage with other regimen mainly ESHAP × 3 cycles followed by high dose therapy with autograft rescue.
Results: A total of 211 (99%) out of 212 patients with low-risk achieved CR. One 74 year old patient died of pneumonia after the third ABVD. A total of 277 (87%) of 315 patients with high-risk achieved CR, 28 PR, 9 failed to respond (FR), and 1 died of sepsis (P<0,001). The estimate EFS at 60 months was 91% and 72% (P< 0.001), while the OSV was 99% and 89% (P=0.001) for low and high risk respectively.
Of the 28 patients with PR, all received second line therapy followed in 17 by an autograft, 13 patients are in CR, 3 are in PR, 1 alive in progressive disease (PD) and 11 died of PD. Of the 9 who FR, five received an autograft, five are alive (CR 3, PR 2) and four died of PD. One patient developed a MDS/AML after relapsing from an autograft and 8 months after having been rescued with BEACOPP. Eight other second cancer (2 NHL, and 6 solid tumours) appeared after treatment, three died and 6 remain alive, 2 in CR of their HL.
Using the IPI HL 205 patients (45%) have scored 0–1, 206 (46%) scored 2–3, and 39 (9%) scored ≥ 4 out of 450 patients. The rate of CR was 97%, 90%, and 87% respectively (P<0.020). The estimated EFS at 60 months was 87%, 76% and 61% respectively (P=0.001). The OSV was 97%, 91% and 78% (P=0.004).
Conclusion: This risk-oriented therapy based in cycles of ABVD and doses of IFRT in 527 patients with HL without previous treatment, produced an overall CR rate of 93%, EFS of 80% and OSV of 93% at 60 months.