Hodgkin lymphoma in the elderly: new perspectives and a 10‐year monocenter real‐life experience

TO THE EDITOR We read with great interest the recently published paper by Engert, that adfirms an improved survival for Hodgkin lymphoma (HL) has been mainly observed in younger patients, while older patients (≥60 years old) have a more aggressive disease characterized by adverse prognostic features, reduced tolerance to chemotherapy and less favourable outcome. Older HL patients appear an understudied category. Since severe comorbidities might preclude curative chemotherapy, Böll and colleagues have suggested to perform a comprehensive geriatric assessment (CGA) including activities of daily living (ADL), instrumental (I) ADL and Cumulative Illness Rating Scale (CIRS) before treatment. Older HL patients treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) experienced lower dose intensity, higher toxicity and treatment-related mortality compared to younger patients. Bleomycin-induced lung toxicity (BLT) was uncommon in patients receiving 2 cycles, while it was severe in 7/69 (10%) patients receiving 4 cycles (3 fatal cases). In the SHIELD study an attempt to reduce treatment intensity was made with VEPEMB regimen (vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone, bleomycin), including only 2 bleomycin doses. However, a randomized trial comparing VEPEMB with ABVD showed the same treatment-related mortality with reduced progression-free survival (PFS) for VEPEMB regimen. At our Institution, we have retrospectively analyzed a cohort of 34 elderly HL patients between 2009 and 2018. PFS was measured from date of treatment initiation to relapse, progression or death; overall survival (OS) was measured from date of treatment initiation to death. Statistical analyses was performed using the software MedCalc v2.0; categorical variables were analyzed using Fisher's exact test, survival analysis was performed by Kaplan-Meier method using the global log-rank test. All patients signed written informed consent in accordance with local Institutional Review Board requirements and the Declaration of Helsinki. Clinical characteristics were collected through chart review and are illustrated in Table 1. All patients completed staging with CT scan and PET. Geriatric assessment was performed in all cases and influenced treatment choice, fit/unfit patients until 70 years old received ABVD (reduced doses for unfit patients), the other unfit patients received VEPEMB regimen, while chlorambucil-vinblastineprocarbazine-prednisone (ChlVPP) was administered to frail patients; 1 HIV positive case received brentuximab vedotin (BV). If indicated, involved field radiotherapy (RT) was administered as consolidation. Final response assessment was done according to the 2007 Revised Response Criteria. Overall, 25/34 cases achieved a CR (4/34 a PR), CR rate and overall response rate (ORR) were 74% and 85%, respectively, median number of cycles was 4 (range 2-6). In early-stage patients, 12/13 achieved a CR (92%), 10/12 received RT as consolidation (1 patient refused and another was defined not suitable for RT). In advanced-stage patients, 13/21 achieved a CR (4/21 a PR), ORR and CR rate were 81% and 60%, respectively. There was a trend to superior CR for ABVD vs other regimes (p=0.05) and to inferior CR for advanced vs early-stage disease (p=0.1). Grade 3-4 neutropenia occurred in 12/34 cases (35%), infectious complications were observed in 9/34 cases (26%, hospitalization required in 2 cases), pulmonary toxicity and nausea were mild to moderate, no treatmentrelated deaths occurred. Grade 3-4 neutropenia and infectious complications rates were comparable for ABVD vs other regimens (8/21 cases, 38% vs 4/13 cases, 30.7% and 6/21 cases, 28.5% vs 3/13 cases, 23%; respectively, p=n.s.). After a median follow-up of 42 months, 24/34 patients (70.5%) were alive, cause of death was progressive disease (3 cases), second neoplasms (2 cases), cardiovascular disease (3 cases), cerebrovascular disease and HIV (1 case each). Out of 9 patients not achieving a CR, 4 received gemcitabine-based therapy (1 patient had early death because of HIV, 1 patient in PR refused treatment and the other 3 cases were frail and received supportive care). One patient, 62 years old, relapsed after ABVD, received ifosfamide, gemcitabine and vinorelbine and was consolidated with autologous transplantation. Estimated 3-year PFS was 62% (Figure 1), 3-year OS was 73%. Advancedstage disease, age>70 years old and unfit/frail status were associated with a trend to reduced PFS. Patients>70 years old and unfit/frail experienced a trend to increased infectious complications (p=0.05). We confirm in our real-life experience elderly HL patients are characterized by less favourable outcome if compared to published data about younger patients. Our study has some limitations, above all it is a retrospective analysis of a small sample size, even if comparable to previously published experiences. We recommend baseline CGA and suggest ABVD could represent a useful option with curative intent for a group of fit patients ≤70 years old. Patients >70 years old or with significant comorbidities are characterized by reduced treatment tolerance and inferior outcome (the lack of significance is probably due to the small sample size); thus we suggest they should receive less intensive regimens such as VEPEMB or ChlVPP. Received: 15 July 2019 Revised: 27 August 2019 Accepted: 28 August 2019 DOI: 10.1002/hon.2675