Patient characteristics, treatment, toxicity, and survival of older early-stage favorable HL patients treated with 2 cycles of AVD (HD13 trial), 2 cycles of ABVD (HD10 and HD13 trials), or 4 cycles of ABVD (HD10 trial)
| . | . | HD13 . | HD10 . | ||
|---|---|---|---|---|---|
| . | . | 2×AVD (n = 82) . | 2×ABVD (n = 67) . | 2×ABVD (n = 70) . | 4×ABVD (n = 68) . |
| Age | Median (range) | 66 (60-75) | 65 (60-74) | 64 (60-74) | 65 (60-75) |
| Gender | Male | 44 (54%) | 38 (57%) | 41 (59%) | 37 (54%) |
| WHO activity index | 0 | 70 (85%) | 59 (88%) | 60/68 (88%) | 58 (85%) |
| 1 | 12 (15%) | 8 (12%) | 8/68 (12%) | 9 (13%) | |
| 2 | 1 (1%) | ||||
| Clinical stage | I | 39 (48%) | 39 (58%) | 27 (39%) | 27 (40%) |
| II | 43 (52%) | 28 (42%) | 43 (61%) | 41 (60%) | |
| Risk factors | B symptoms | 10 (12%) | 3 (4%) | 6 (9%) | 7 (10%) |
| Bulk | 15 (18%) | 10 (15%) | 21 (30%) | 20 (29%) | |
| Infradiaphragmatic involvement | 13/81 (16%) | 11 (16%) | 11 (16%) | 11/66 (17%) | |
| Histology | Mixed cellularity | 39/71 (55%) | 27/57 (47%) | 36/66 (55%) | 37/63 (59%) |
| Nodular sclerosis | 14/71 (20%) | 18/57 (32%) | 16/66 (24%) | 13/63 (21%) | |
| Lymphocyte-rich | 13/71 (18%) | 8/57 (14%) | 7/66 (11%) | 4/63 (6%) | |
| Nodular lymphocyte-predominant | 3/71 (4%) | 2/57 (4%) | 5/66 (8%) | 5/63 (8%) | |
| Classical HL numbers | 2/71 (3%) | 2/57 (4%) | 2/66 (3%) | 4/63 (6%) | |
| Early termination of protocol treatment | Total | 2 (2%) | 2 (3%) | 3 (4%) | 12 (18%) |
| During chemotherapy | 1 (1%) | 1 (1%) | 4 (6%) | ||
| After chemotherapy, but before radiotherapy | 1 (1%) | 2 (3%) | 6 (9%) | ||
| During or after radiotherapy | 1 (1%) | 1 (1%) | 2 (3%) | ||
| Reason for early termination | Toxicity | 9 (13%) | |||
| Patient’s wish | 1 (1%) | 1 (1%) | 1 (1%) | ||
| Progression | 1 (1%) | 1 (1%) | |||
| Disease-related | 1 (1%) | ||||
| Other/unknown | 1 (1%) | 1 (1%) | 1 (1%) | 1 (1%) | |
| Chemotherapy | Patients with complete documentation | 79 (96%) | 63 (94%) | 69 (99%) | 67 (99%) |
| Correct number of chemotherapy cycles | 79/79 (100%) | 62/63 (98%) | 66/69 (96%) | 91/67 (91%) | |
| Total relative chemotherapy dose (mean ± SD) | 99 ± 3% | 97 ± 8% | 103 ± 21% | 93 ± 11% | |
| Chemotherapy delay (mean ± SD) | 0.6 ± 0.8 wk | 0.8 ± 1.0 wk | 0.9 ± 1.1 wk | 2.1 ± 2.1 wk | |
| Acute toxicity of chemotherapy | No. of patients “as treated” | 79 | 62 | 66 | 70 |
| Any grade III/IV event* | 31/77 (40%) | 26/62 (42%) | 24/65 (37%) | 45/69 (65%) | |
| Leukopenia | 18/77 (23%) | 18/62 (29%) | 14/65 (22%) | 26/69 (38%) | |
| Hair loss | 16/77 (21%) | 9/62 (15%) | 11/65 (17%) | 24/69 (35%) | |
| Nausea or vomiting | 6/77 (8%) | 2/62 (3%) | 5/65 (8%) | 9/69 (13%) | |
| Infection | 2/77 (3%) | 4/62 (6%) | 5/65 (8%) | 8/69 (12%) | |
| Pain | 4/77 (5%) | 2/62 (3%) | 3/65 (5%) | 2/69 (3%) | |
| Respiratory tract disorders including BLT | 1/62 (2%) | 1/65 (2%) | 7/69 | ||
| Response to treatment | Complete remission with or without residual abnormalities | 80 (98%) | 66 (99%) | 67 (96%) | 60 (88%) |
| Partial remission | 2 (3%) | 1 (1%) | |||
| Progressive disease | 1 (1%) | 1 (1%) | |||
| Unknown† | 1 (1%) | 1 (1%) | 7 (10%) | ||
| Observation time | Median | 57 mo | 58 mo | 84 mo | 84 mo |
| Progression/relapse | Any event | 11 (13%) | 6 (9%) | 7 (10%) | 8 (12%) |
| Progression | 1 (1%) | 1 (1%) | |||
| Early relapse | 2 (2%) | 1 (1%) | 2 (3%) | 1 (1%) | |
| Late relapse | 8 (10%) | 5 (7%) | 4 (6%) | 7 (10%) | |
| Reason of death | Total | 12 (15%) | 8 (12%) | 16 (23%) | 15 (22%) |
| HL | 2 (3%) | 2 (3%) | |||
| Toxicity of first-line or salvage therapy | 1 (1%) | 2 (3%) | 4 (6%) | ||
| Second malignancy | 4 (5%) | 1 (1%) | 6 (9%) | ||
| Cardiovascular disease | 3 (4%) | 5 (7%) | |||
| Respiratory | 2 (2%) | 1 (1%) | 1 (1%) | 1 (1%) | |
| Other disease | 1 (1%) | 2 (3%) | 4 (6%) | ||
| Accident | 1 (1%) | ||||
| Unclear | 4 (5%) | 1 (1%) | 1 (1%) | 2 (3%) | |
| Progression-free survival | 5-y estimate (95% CI) | 79% (69-89) | 78% (66-89) | 79% (70-89) | 79% (70-89) |
| 5-y difference, other - 2×ABVD (95% CI) | 2% (−14 to 17) | 0% (−14 to 14) | |||
| Hazard ratio, other vs 2×ABVD (95% CI) | 1.28 (0.63-2.59) | 1.09 (0.58-2.04) | |||
| Overall survival | 5-y estimate (95% CI) | 91% (84-98) | 86% (77-96) | 84% (76-93) | 87% (79-95) |
| 5-y difference, other −2×ABVD (95% CI) | 5% (−7 to 17) | 3% (−9 to 14) | |||
| Hazard ratio, other vs 2×ABVD (95% CI) | 1.30 (0.53-3.20) | 0.97 (0.48-1.96) | |||
| . | . | HD13 . | HD10 . | ||
|---|---|---|---|---|---|
| . | . | 2×AVD (n = 82) . | 2×ABVD (n = 67) . | 2×ABVD (n = 70) . | 4×ABVD (n = 68) . |
| Age | Median (range) | 66 (60-75) | 65 (60-74) | 64 (60-74) | 65 (60-75) |
| Gender | Male | 44 (54%) | 38 (57%) | 41 (59%) | 37 (54%) |
| WHO activity index | 0 | 70 (85%) | 59 (88%) | 60/68 (88%) | 58 (85%) |
| 1 | 12 (15%) | 8 (12%) | 8/68 (12%) | 9 (13%) | |
| 2 | 1 (1%) | ||||
| Clinical stage | I | 39 (48%) | 39 (58%) | 27 (39%) | 27 (40%) |
| II | 43 (52%) | 28 (42%) | 43 (61%) | 41 (60%) | |
| Risk factors | B symptoms | 10 (12%) | 3 (4%) | 6 (9%) | 7 (10%) |
| Bulk | 15 (18%) | 10 (15%) | 21 (30%) | 20 (29%) | |
| Infradiaphragmatic involvement | 13/81 (16%) | 11 (16%) | 11 (16%) | 11/66 (17%) | |
| Histology | Mixed cellularity | 39/71 (55%) | 27/57 (47%) | 36/66 (55%) | 37/63 (59%) |
| Nodular sclerosis | 14/71 (20%) | 18/57 (32%) | 16/66 (24%) | 13/63 (21%) | |
| Lymphocyte-rich | 13/71 (18%) | 8/57 (14%) | 7/66 (11%) | 4/63 (6%) | |
| Nodular lymphocyte-predominant | 3/71 (4%) | 2/57 (4%) | 5/66 (8%) | 5/63 (8%) | |
| Classical HL numbers | 2/71 (3%) | 2/57 (4%) | 2/66 (3%) | 4/63 (6%) | |
| Early termination of protocol treatment | Total | 2 (2%) | 2 (3%) | 3 (4%) | 12 (18%) |
| During chemotherapy | 1 (1%) | 1 (1%) | 4 (6%) | ||
| After chemotherapy, but before radiotherapy | 1 (1%) | 2 (3%) | 6 (9%) | ||
| During or after radiotherapy | 1 (1%) | 1 (1%) | 2 (3%) | ||
| Reason for early termination | Toxicity | 9 (13%) | |||
| Patient’s wish | 1 (1%) | 1 (1%) | 1 (1%) | ||
| Progression | 1 (1%) | 1 (1%) | |||
| Disease-related | 1 (1%) | ||||
| Other/unknown | 1 (1%) | 1 (1%) | 1 (1%) | 1 (1%) | |
| Chemotherapy | Patients with complete documentation | 79 (96%) | 63 (94%) | 69 (99%) | 67 (99%) |
| Correct number of chemotherapy cycles | 79/79 (100%) | 62/63 (98%) | 66/69 (96%) | 91/67 (91%) | |
| Total relative chemotherapy dose (mean ± SD) | 99 ± 3% | 97 ± 8% | 103 ± 21% | 93 ± 11% | |
| Chemotherapy delay (mean ± SD) | 0.6 ± 0.8 wk | 0.8 ± 1.0 wk | 0.9 ± 1.1 wk | 2.1 ± 2.1 wk | |
| Acute toxicity of chemotherapy | No. of patients “as treated” | 79 | 62 | 66 | 70 |
| Any grade III/IV event* | 31/77 (40%) | 26/62 (42%) | 24/65 (37%) | 45/69 (65%) | |
| Leukopenia | 18/77 (23%) | 18/62 (29%) | 14/65 (22%) | 26/69 (38%) | |
| Hair loss | 16/77 (21%) | 9/62 (15%) | 11/65 (17%) | 24/69 (35%) | |
| Nausea or vomiting | 6/77 (8%) | 2/62 (3%) | 5/65 (8%) | 9/69 (13%) | |
| Infection | 2/77 (3%) | 4/62 (6%) | 5/65 (8%) | 8/69 (12%) | |
| Pain | 4/77 (5%) | 2/62 (3%) | 3/65 (5%) | 2/69 (3%) | |
| Respiratory tract disorders including BLT | 1/62 (2%) | 1/65 (2%) | 7/69 | ||
| Response to treatment | Complete remission with or without residual abnormalities | 80 (98%) | 66 (99%) | 67 (96%) | 60 (88%) |
| Partial remission | 2 (3%) | 1 (1%) | |||
| Progressive disease | 1 (1%) | 1 (1%) | |||
| Unknown† | 1 (1%) | 1 (1%) | 7 (10%) | ||
| Observation time | Median | 57 mo | 58 mo | 84 mo | 84 mo |
| Progression/relapse | Any event | 11 (13%) | 6 (9%) | 7 (10%) | 8 (12%) |
| Progression | 1 (1%) | 1 (1%) | |||
| Early relapse | 2 (2%) | 1 (1%) | 2 (3%) | 1 (1%) | |
| Late relapse | 8 (10%) | 5 (7%) | 4 (6%) | 7 (10%) | |
| Reason of death | Total | 12 (15%) | 8 (12%) | 16 (23%) | 15 (22%) |
| HL | 2 (3%) | 2 (3%) | |||
| Toxicity of first-line or salvage therapy | 1 (1%) | 2 (3%) | 4 (6%) | ||
| Second malignancy | 4 (5%) | 1 (1%) | 6 (9%) | ||
| Cardiovascular disease | 3 (4%) | 5 (7%) | |||
| Respiratory | 2 (2%) | 1 (1%) | 1 (1%) | 1 (1%) | |
| Other disease | 1 (1%) | 2 (3%) | 4 (6%) | ||
| Accident | 1 (1%) | ||||
| Unclear | 4 (5%) | 1 (1%) | 1 (1%) | 2 (3%) | |
| Progression-free survival | 5-y estimate (95% CI) | 79% (69-89) | 78% (66-89) | 79% (70-89) | 79% (70-89) |
| 5-y difference, other - 2×ABVD (95% CI) | 2% (−14 to 17) | 0% (−14 to 14) | |||
| Hazard ratio, other vs 2×ABVD (95% CI) | 1.28 (0.63-2.59) | 1.09 (0.58-2.04) | |||
| Overall survival | 5-y estimate (95% CI) | 91% (84-98) | 86% (77-96) | 84% (76-93) | 87% (79-95) |
| 5-y difference, other −2×ABVD (95% CI) | 5% (−7 to 17) | 3% (−9 to 14) | |||
| Hazard ratio, other vs 2×ABVD (95% CI) | 1.30 (0.53-3.20) | 0.97 (0.48-1.96) | |||
CI, confidence interval; SD, standard deviation; WHO, World Health Organization.
Including anemia, thrombopenia, mucositis, drug fever, allergy, heart, skin, nervous system, and gastrointestinal and urogenital tract disorders.
Death after treatment termination from acute toxicity (4 cases in the 4×ABVD group), no further information after end of treatment (1 case each in 4×ABVD and HD13/2×ABVD groups), intensified therapy at unknown tumor status (1 case each in 4×ABVD and 2×AVD groups), and no further information after early treatment termination (1 case in the 4×ABVD group).