Doxorubicin, vinblastine, dacarbazine and lenalidomide for older Hodgkin lymphoma patients: final results of a German Hodgkin Study Group (GHSG) phase‐I trial

Abstract

Summary About 30% of all Hodgkin lymphoma (HL) patients are ≥60 years old. As lenalidomide has promising single agent activity in multiple relapsed HL, we replaced bleomycin in ABVD with lenalidomide in this phase‐I trial. Patients aged ≥60 years with early‐unfavourable‐ or advanced‐stage HL (Eastern Cooperative Oncology Group performance status ≤2, Cumulative Illness Rating Scale for Geriatrics score 0–7) received 4–8 cycles of AVD (doxorubicin, vinblastine, dacarbazine) and lenalidomide in escalation with overdose control. Dose‐limiting toxicities (DLTs) included thromboembolism ≥grade 2, severe haematological toxicity, neutropenic fever and prolonged therapy delay. Twenty‐five patients with a median age of 68 years were included, 68% had advanced‐stage HL. A pre‐defined stopping criterion for dose escalation after DLT evaluation of 20/24 patients suggested a recommended phase II dose (RPTD) of 20 mg. DLTs occurred in 10/24 evaluable patients, all treated with ≥20 mg, however, median relative dose intensity was 97% (interquartile range 49–104%). Grade 3 or higher toxicities occurred in all 22 patients at ≥20 mg lenalidomide but no treatment‐related deaths occurred. Overall response rate was 80% for all patients (20/25) and 86% (19/22) at ≥20 mg lenalidomide. Three‐year estimates for progression‐free survival and OS were 69·7% (95% CI: 50·3–89·1%) and 83·8% (95%‐CI: 69·3–98·4%), respectively. In conclusion, AVD with lenalidomide 20 mg is feasible and highly effective in older HL patients.

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

“…In a recent trial, BV was associated with cyclophosphamide, doxorubicin and prednisone (B‐CAP); 1‐year PFS was 73.9%, grade 4 leukopenia and grade 3 peripheral neuropathy were observed in 41% and 20% of cases, respectively . Lenalidomide was investigated in combination with AVD in 25 elderly HL patients with CIRS 0‐7; 3‐year estimated PFS was 69.7% without treatment‐related deaths …”

Comorbidity assessment to determine prognosis in older adult patients with classical Hodgkin lymphoma

“…Among these drugs, brentuximab has been explored either in combination with AVD in fit patients or with dacarbazine alone in patients with severe comorbidity, showing promising activity . Other drugs that are explored in this setting include lenalidomide and nivolumab …”

“…[26][27][28] Other drugs that are explored in this setting include lenalidomide and nivolumab. 29,30 We also analyzed cause-specific survival. Our finding that the type of chemotherapy and the prognostic score were associated with lymphoma-specific survival and that the presence of severe comorbidity was associated with mortality form all other causes other than lymphoma was not unexpected.…”

Partial omission of bleomycin for early‐stage Hodgkin lymphoma patients treated with combined modality therapy: Does incomplete ABVD lead to inferior outcomes?

“…As 14% of deaths were related to lung toxicity, the authors recommend bleomycin dose reduction or removal [9]. A phase I trial attempted to replace bleomycin with lenalidomide for Hodgkin lymphoma patients aged 60 years or above, and concluded that this approach was feasible and highly effective [10].…”