ABSTRACT: Patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) following autologous stem cell transplant (ASCT) remain a management challenge with few reliably effective treatments. Lenalidomide, an immunomodulatory drug approved for patients with myelodysplastic syndrome with del(5q), multiple myeloma, and mantle cell lymphoma, has demonstrated some activity in patients with R/R cHL, though the toxicity of traditional doses and schedules has been a barrier to consistent use. Low dose continuous (LDC) schedules have emerged as promising, with a more favorable safety profile. We report herein that LDC schedules are associated with a far more tolerable toxicity profile, and exhibit at least equivalent efficacy in this patient population. We report that patients diagnosed with R/R cHL who previously underwent, or were not candidates for, ASCT and/or clinical trials, were administered daily LDC lenalidomide (20?mg orally with dose reduction for toxicity). Among the 19 patients included in this analysis, 11% of patients achieved a partial response (PR), with no documented complete responses (CR). A total of 12 (63%) patients maintained stable disease (SD), with 7 patients (37%) remaining in SD for more than 6?months. The clinical benefit rate (comprised of CR, PR, and SD for greater than 6?months) was 47% (7 out of 19 patients). The median progression-free survival and overall survival of all patients were 9.4?months (range, 4.6-14.4?months) and 90?months (range, 63.6-166.8?months), respectively. In general, the treatment was well tolerated, with grade 3 or 4 adverse events consisting of neutropenia (n?=?4), and one case each of thrombocytopenia, fatigue, rash, creatinine elevation, aspartate transaminase/alanine transaminase elevation, and treatment related secondary malignancy. In a heavily treated R/R cHL patient population, daily LDC lenalidomide was associated with a high disease control rate with a favorable toxicity profile.