A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma

Abstract

Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

Figure 1

Summary of lenalidomide administration. Graphical summary of lenalidomide administration to 38 cHL patients, with individual patients on the y-axis and the number of cycles and dose of lenalidomide administered on the x-axis. If an intra-cycle dose reduction was performed, the lowest dose used for a given cycle is indicated. Lenalidomide was administered on days 1-21 of a 28-day cycle, initiated at 25 mg/d. *Ongoing lenalidomide therapy.

Figure 2

Waterfall plot of maximal decrease in sum of the products of the greatest diameter from baseline (before therapy) for 35 cHL patients treated with ≥ 2 cycles of lenalidomide. Two patients who went off-study during cycle 1 or 2 of lenalidomide because of AEs are not included, and off-study data from 1 patient with rapidly progressive disease during cycle 1 were not available. Patients with CR, PR, or SD > 6 months are annotated.

Figure 3

Kaplan-Meier PFS and OS estimates. Survival analysis included 35 patients with evaluable disease completing at least 2 cycles of lenalidomide. Median PFS was 4 months (95% CI: 2-6) and the median OS was 20 months (95% CI: 15-NE).

Figure 4

CCL17/TARC and CCL22/MDC changes. Shown are CCL17/TARC and CCL22/MDC changes from pretherapy cycle 1 day 1 (C1D1) and cycle 1 day 15 (C1D15) for responders (CR/PR/SD ≥ 6 months) and nonresponders (SD < 6 months, PD). Box-whisker plots depict pretherapy and C1D15 plasma CCL17 or CCL22 concentrations. P values were determined using the Wilcoxon signed rank test. There was no significant difference between C1D1 and C1D15 in nonresponders.