Phase II Trial of Lenalidomide in Patients with Relapsed or Refractory Hodgkin Lymphoma

Introduction: Patients (pts) with Hodgkin Lymphoma (HL) that has relapsed after or is refractory to primary therapy and subsequent high dose chemotherapy with autologous stem cell transplantation (ASCT) cannot be cured with conventional treatments. As various cytokines (IL-6,12 and 13), NF-KB and angiogenic factors have been implicated in the pathophysiology of HL, we postulated that lenalidomide, a novel agent with both immunomodulatory and anti-angiogenic properties would have activity in the relapsed (REL) or refractory (REF: defined as progression on or within 3 months of primary therapy) setting.

Methods: The treatment regimen consisted of lenalidomide 25 mg PO days 1–21 on a 28 day cycle. CT scans of the chest, abdomen and pelvis were obtained at baseline and were repeated every 2 cycles or earlier at the investigators’ discretion. A Fleming two stage trial design was chosen and a calculated sample size of 30 was determined based on an alpha error < 0.05 and power of 0.80 and a response proportion of 0.20 to consider lenalidomide active. Serum/plasma specimens at baseline and on treatment were collected for cytokine analysis. Data analysis was performed in July 2008 after the first stage (15 patients) were accrued. Responses were categorized by International Workshop Criteria (Cheson JCO 1999) and toxicity was assessed by NCI common toxicity criteria v3.0.

Results: 15 pts have been accrued with 14 evaluable patients to date. The median age was 37 (range 18–74) with 7 female pts. ECOG performance status was 0: (2) 1: (9) and 2: (4). The median number of prior chemotherapy regimens was 2 (range 1–4). All pts (except one pt on a pediatric protocol had received ABVD-type primary chemotherapy and 9/15 received prior radiotherapy. 10 pts had undergone prior ASCT with 10 patients having REF and 5 pts with REL disease following primary chemotherapy. 8 pts had disease recurrence within 1 year post ASCT. Of non-ASCT pts, 2 pts were refractory to chemotherapy and 3 pts were ineligible (age and/or comorbidity). The median number of treatment cycles/pt was 3 (range 0–10) with 1 pt enrolled but not starting therapy due to rapid disease progression. Best response was a PR in 2 cases (confirmed by 3^rd independent radiologist in 1), and SD in 7 pts. Six pts discontinued therapy because of PD and 5 for toxicity; 4 pts remain on treatment. Median time to progression was 3.2 months and overall survival was 9.1 months. Grade 3–4 toxicities included: neutropenia:4 (1 pt had febrile neutropenia following 1 cycle of treatment), thrombocytopenia:4 and anemia:3. Five pts developed skin rash (2: grade 2) and there was 1 case of erythema multiforme.

Conclusions: Preliminary results of this phase II study including heavily pre-treated pts with HL suggest lenalidomide has some evidence of activity. Toxicity is manageable although hematologic side effects are common. These results suggest that lenalidomide warrants further study and the second stage of accrual is ongoing.