Treatment practices and outcomes of advanced stage classical Hodgkin lymphoma in India: An analysis from the hematology cancer consortium

Abstract This retrospective study evaluated treatment practices and outcomes in patients with advanced stage classical Hodgkin lymphoma (cHL) in India, across 10 centers of the Hematology Cancer Consortium. It included patients treated between January 2020 – December 2023, with one center contributing data from 2018. A total of 1524 patients were diagnosed with cHL at these centers, of whom 876 had advanced stage disease (Ann Arbor stage IIBX–IV). Among these, 703 patients opted to continue treatment at the reporting institutions. The median age was 34 years; 466(66.2%) had B symptoms, 445(63.3%) had stage IV disease, 146(21%) had bulky disease, and 306(44%) had extra nodal involvement. The most commonly used chemotherapy protocol was ABVD in 628 (89%) patients. Other regimens included BEACOPP (n=39; 5.5%), platinum-based protocols (n=8; 1.1%), and regimens with Brentuximab Vedotin (n=3; 0.4%) or Nivolumab (n=7; 1.0%). Of the 703 patients who initiated treatment, interim response assessment was available for 586 (84%) patients. Among these, 471 underwent interim response assessment using FDG-PET/CT, while the remaining were assessed using CT or ultrasound. PET-based assessments reported Deauville scores (DS) of 1–3 in 372 (84%) patients, DS4 in 53 (12%) patients, and DS5 in 17 (3.8%) patients. Bleomycin toxicity was reported in 48 (7%) patients and 4 patients succumbed to the same. A total of 21 (2.9%) patients died during the treatment period. End-of-treatment (EOT) response was available for 590 patients: 481 (68.4%) achieved complete response (CR), 54 (7.7%) achieved partial response (PR), progressive disease (PD) in 55 (7.8%); data was not available for 113(16.1%) patients. Radiotherapy was administered at end of therapy in 122 patients (18%): 43 patients received it as part of the initial treatment plan for bulk disease, and 56 patients received it for residual disease following chemotherapy. At a median follow-up of 27 months (estimated by reverse Kaplan–Meier), 458 patients (65%) were in complete remission, 146 (21.1%) were not in CR, 37 (5.3%) had died, and disease status was unavailable for 62 (8.8%) patients. The 2-year event-free survival (EFS) for the entire cohort (n=703) was 79.3 ± 1.7%. EFS was 87.8 ± 1.9% for iPET2-negative (DS1–3), 61.2 ± 7.8% for DS4, and 50.5 ± 14.8% for DS5 (p < 0.001).A low International Prognostic Score (IPS) (0–3) was associated with superior 2-year EFS (86.9 ± 3.1%) compared to a high IPS score (>3), which had an EFS of 77.7 ± 3.0% (p = 0.022). In a univariate analysis of all prognostic variables included in the original Hasenclever analysis, albumin < 4 gm/dL(HR 2.51; p<0.001) and hemoglobin < 10.5 gm/dl (HR 3.35; p<0.001) were associated with an inferior event-free survival Additional parameters significantly associated with EFS included iPET2 DS score 4–5(HR 4.15; p<0.001),WBC count ≤4000/mm³(HR 1.70; p = 0.018) and elevated LDH(HR 1.53; p = 0.031). On the Multivariate Cox Proportional Hazards (PH) Model, only the iPET retained prognostic significance for EFS (HR 3.92; p<0.001) . EFS varied significantly when stratified by both IPS and iPET response. Patients with IPS low (0-3) and iPET negative (DS1-3) had the most favourable outcomes, with a 2-year EFS of 90.3 ± 2.9%. In contrast, those with iPET positivity, regardless of IPS score, had inferior outcomes—EFS of 54± 8.5% in IPS high and 62 ± 13.7 % in IPS low patients. Patients with a high IPS and iPET negativity had intermediate outcomes, with an EFS of 84.4 ± 3%. The difference in EFS across the four groups was statistically significant (p < 0.001), highlighting the combined prognostic value of IPS score and iPET2 response. In this large multi-center cohort from India, ABVD remains the predominant regimen for advanced-stage cHL , achieving a 2-year EFS of 79%. iPET response was the strongest predictor of event-free survival, outperforming traditional prognostic markers like the IPS score. Combining iPET and IPS can be further used to stratify risk, though this requires validation in prospective cohorts.