IMPACT OF PRIOR TREATMENT ON PFS FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA PATIENTS RANDOMIZED TO LENALIDOMIDE VS INVESTIGATOR’S CHOICE: A SUBGROUP ANALYSIS OF THE PHASE II MCL-002 (SPRINT) STUDY

Background
Clinically meaningful and statistically significant improved activity was shown for lenalidomide, an immunomodulator with antineoplastic and antiproliferative effects, over single-agent investigator choice (IC) treatment in the MCL-002 (SPRINT) study of relapsed/refractory (R/R) patients with mantle cell lymphoma (MCL).

Aims
Evaluate the potential impact of prior therapy on progression-free survival (PFS) in R/R MCL patients randomized to lenalidomide vs IC.

Methods
Patients were randomized to lenalidomide (25 mg/day PO on days 1-21/28 days) or single-agent IC (rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine). The primary endpoint of this phase II study was PFS; prespecified exploratory analyses of PFS by subgroups were conducted.

Results
Following a median of 2 prior therapies, 254 R/R MCL patients were randomized 2:1 to lenalidomide (n=170) or IC (n=84). The preferred single-agent IC therapy was selected for each patient prior to randomization. Overall, the median PFS was significantly improved for lenalidomide vs IC (8.7 vs 5.2 months; HR=0.61, P=0.004). Exploratory analysis of PFS by central review based on selected IC treatment showed that lenalidomide provided a reduction in the risk of progression or death vs each IC treatment. Compared with lenalidomide and taking into account small patient numbers per IC group, the risk reduction in PFS was 22% vs rituximab (n=27), 56% vs gemcitabine (n=20), 42% vs fludarabine (n=18), 43% vs chlorambucil (n=11), and 8% vs cytarabine (n=8).

 

Subgroup analysis of PFS by central review based on prior treatment-related subgroups favored the use of lenalidomide overall. Several subgroups showed statistically improved PFS for lenalidomide over IC, including patients with ≥2 prior systemic antilymphoma therapies, >1 prior relapse, refractory to last prior treatment, prior rituximab exposure, no prior hyperCVAD±rituximab or stem cell transplantation, ≥6 months time from last therapy (≥230 days from last prior rituximab), and <3 years from diagnosis to study treatment. The only category without risk reduction (but statistically insignificant) was ≥4 prior systemic antilymphoma therapies, partly explained by low patient numbers in each arm.

 

Treatment group was the main effect associated with significantly better PFS by univariate Cox regression analysis (HR=0.619; P=0.004), and was highly significant in the multivariate analysis (HR=0.384). Other factors associated with significantly better PFS by both univariate and multivariate analysis were <3 prior systemic antilymphoma therapies, and ≥230 days from last prior rituximab.

Summary
Subgroup and regression analyses of the primary study endpoint PFS showed superiority for lenalidomide over IC therapy in providing consistent clinical benefit in patients with R/R MCL irrespective of prior treatment history.

Keyword(s): Imids, Mantle cell lymphoma

www.eha.org