The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496

Abstract

There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0·3% for patients aged <60 years (P < 0·001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P = 0·002; 5-year overall survival: 58% and 90%, respectively, P < 0·0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P = 0·37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, P = 0·30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P < 0·0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.

Trial registration: ClinicalTrials.gov NCT00003389.

Figure 1. Older Hodgkin lymphoma (HL) patient survival

The (A) failure-free survival (FFS) and (B) overall survival (OS) for all older HL patients. The (C) 3- and 5-year FFS for older patients who received ABVD was 58% and 53%, respectively, which compared with 54% and 42%, respectively, for patients who received Stanford V (p=0.99); while the (D) 3- and 5-year OS for older patients who received ABVD was 73% and 64%, respectively, which compared with 67% and 51%, respectively, for patients who received Stanford V (p=0.90).

Figure 2. Survival for older Hodgkin lymphoma (HL) patients based on International Prognostic Score (IPS) and including competing risk analysis

There were no significant differences in (A) failure-free survival and (B) overall survival according to IPS for older HL patients. The (C) cumulative incidence of death due to HL/progression and death due to HL treatment/toxicity (i.e., treatment-related mortality) vs death incidence rate due to all other causes. The associated cumulative incidence of death at 3 and 5 years for older HL patients was 23% and 30%, respectively vs 7% and 12%, respectively, for all other causes. The (D) cumulative incidence of death due to HL treatment/toxicity was plotted separately. The associated 3- and 5-year incidences of death was 16% and 21%, respectively, due to HL/progression, 7% and 9%, respectively, due to toxicity, and 7% and 12%, respectively, due to other causes.

Figure 3. Outcomes comparing older HL with younger patients

The (A) 3- and 5-year failure-free survival for patients aged ≥60 years was 56% and 48%, respectively, which compared with 76% and 74%, respectively, for patients aged <60 years (p=0.002); while (B) the 3- and 5-year overall survival for patients aged ≥60 years was 70% and 58%, respectively, which compared with 93% and 90%, respectively, for patients aged <60 years (p<0.0001). (C) The 2- and 5-year time-to-progression (TTP) for patients aged ≥60 years was 80% and 68%, respectively; this compared with 81% and 78%, respectively, for patients aged <60 years (p=0.37). (D) The rates of progression were determined with competing risk analysis because death without progression is a competing risk for disease progression. The incidence rates of progression including competing risks for patients aged ≥60 years at 2 and 5 years were 19% and 30%, respectively, compared with 19% and 23%, respectively, for patients aged <60 years (p=0.30); however, the incidence rates of death without progression for patients aged ≥60 years at 2 and 5 years were 13% and 22%, respectively, compared with 2% and 9%, respectively, for patients aged <60 years (p=<0.0001).