Initial Experience with Lenalidomide As Consolidation Treatment in Patients with Chronic Lymphocytic Leukemia and Residual Disease After Chemotherapy,
Authors: Pozadzides Jenny V. , Keating Michael J , Wierda William G. , O'Brien Susan , Burger Jan A. , Jorgensen Jeffrey L. , Calin Steliana , Wang SA , Lerner Susan , Ferrajoli Alessandra 
Published: October 2019

Abstract
Abstract 3907
After treatment with purine analog-based combination chemoimmunotherapy, 40% to 60% of patients with CLL have residual disease. As the extent of the residual disease often correlates with time to progression, eradication of residual disease may improve the duration of remission. Although alemtuzumab has been used as consolidation therapy with improvement of responses in 56% of the patients (pts) (Montillo et al, 2006), its use as been limited by concerns of immunosuppression. Lenalidomide is an oral agent with activity in pts with CLL. Lenalidomide's easy oral administration and its immunomodulatory properties make it an interesting agent to be evaluated as consolidation therapy. We, therefore, designed a phase II study to evaluate the efficacy and toxicity of lenalidomide for treatment of residual disease after chemotherapy. Pts with stable PR (at two time assessments at least 3 months apart), nodular PR (nPR), or CR with evidence of disease on immunophenotyping were eligible. Pts were required to enroll between 3 and 9 months after completion of combination chemotherapy. Pts received lenalidomide 10mg daily for 12 months (the first 12 pts in this trial received lenalidomide for 3 months, and the study was then amended to allow up to 12 months of therapy). Early discontinuation of treatment was allowed if pts achieved negativity for minimal residual disease (MRD) before 12 months. Responses were evaluated at 4 months and 12 months according to 1996 NCI-WG criteria. Bone marrow biopsy and BM immunophenotyping by multicolor flow cytometry (MFC) with quantification of residual disease were performed at the time of response assessment. The MFC assay used has a sensitivity of 0.02% (20 aberrant cells/100,000 total cells analyzed). Twenty-six pts have been enrolled in this study, and 21 are evaluable for response. Three pts discontinued treatment within the first 28 days (after 2, 7, and 21 days of therapy) and 2 pts are too early for response assessment. The median age is 62 years (range, 41–76), median number of prior treatment was 2 (range, 1–12). Six pts entered the study in CR, 8 pts had nPR and 12 pts were in PR. The outcome of lenalidomide consolidation and duration of therapy are summarized in the table.Pt #Latest chemotherapyResponse at start of lenalidomideDuration of therapyResponse at end of lenalidomide1FCRCR2 daysNot evaluable2OFARCR49 daysProgression3FCRCR21 daysNot evaluable4R-hyperCVADCR12 monthsCR, MRD +5FCRCR5 monthsCR, MRD +6FBRCR10 days +Too early7FCMRnPR3 monthsCR, MRD +8FCRnPR3 monthsnPR9R-CHOPnPR3 monthsCR, MRD −10CFARnPR3 monthsCR, MRD −11R-hyperCVADnPR12 monthsnPR12FCRnPR3 monthsnPR13FCR bevacizumabnPR12 monthsnPR14FCR bevacizumabnPR4 monthsnPR15OFARPR3 monthsCR, MRD −16CFARPR3 monthsPR17PCRPR3 monthsPR18FCRPR3 monthsnPR19FCRPR3 monthsPR20FCRPR6 monthsnPR21FCR bevacizumabPR9 months +CR, MRD +22FCRPR9 months +PR23FCRPR8 months +PR24FCRPR7 daysNot evaluable25FCR bevacizumabPR7 months +PR26FCRPR3 months +Too early
For the 6 pts in CR at study initiation: 2 pts had no changes in MRD status, 1 pt had disease progression, 2 pts are not evaluable due to early discontinuation and 1 pt has not had enough time on study. For the 8 pts with an nPR: 3 improved response to CR (2 of them MRD negative) and 5 pts had stable nPR. For the 12 pts with a PR: 2 pts improved to a CR (1 of them MRD negative), 2 pts to a nPR, 5 pts remained in PR, 1 pt is not evaluable due to early discontinuation and 1 pt has not had enough time on study. At a median follow up of 23 months, the median time to progression has not been reached in the 7 pts that improved their response as a result of th, and 5 pts remain in remission between 18 and 35 months after therapy. The most common lenalidomide-related adverse event was myelosuppression: grade 3–4 neutropenia (8 pts, 31%) and grade 3–4 thrombocytopenia (2 pts, 8%). Infections occurred in 5 patients: 3 pneumonia (1 RSV, 1 Pseudomonas and 1 unknown pathogen), 1 vaginal Herpes, 1 sinusitis. One patient experienced a grade 4 PE. Other common grade 1–2 toxicities considered lenalidomide-related were fatigue (8 pts, 31%), rash (8 pts, 31%), constipation (4 pts, 15%), diarrhea (4 pts, 15%), cough (3 pts, 8%) and body aches (3 pts, 8%). Based on our early experience, lenalidomide consolidation after chemotherapy can further improve responses in 27% of patients with CLL. Elimination of MRD was seen in 12% of patients treated. Enrollment to this study is ongoing.

Disclosures:
Keating: Celgene: Consultancy. O'Brien:Celgene: Consultancy. Ferrajoli:Celgene: Research Funding.