A comparison of response in the presence or absence of a delay in induction therapy with bortezomib, lenalidomide, and dexamethasone.

Purpose: Lenalidomide, bortezomib, and dexamethasone (RVd) has emerged as a preferred induction therapy in multiple myeloma (MM) in the United States. Due to lenalidomide's teratogenic risk, patients and prescribers must comply with a risk evaluation and mitigation strategy (REMS) program. The REMS program limits dispensing to certain third-party specialty pharmacies, whose average prescription fill times are longer than in-house specialty pharmacies. In practice, a delay in procurement of lenalidomide may mean that patients start therapy with only bortezomib and dexamethasone, delaying the start of more effective triplet therapy. The primary objective of this study is to determine if a delay from start of bortezomib and dexamethasone to start of triplet therapy with lenalidomide impacts rate of achievement of very good partial response (VGPR) after four cycles of RVd.

Methods: This was a single-center retrospective review of adults with newly diagnosed MM who received RVd induction therapy at University of North Carolina Medical Center between April 2014 and June 2017. Patients who started lenalidomide ≥10 days after bortezomib comprised the "Delay" group, while those who started lenalidomide concurrently with bortezomib or within 1-9 days after bortezomib comprised the "No Delay" group. The primary outcome was VGPR or better response rate after four cycles of RVd.

Results: Thirty-eight patients met inclusion criteria. Nine patients (23.7%) experienced any delay in initiation of lenalidomide, with a mean delay of 7.8 days (range 1-18). Four patients (10.5%) experienced a delay ≥10 days. No patients in the Delay group were of reproductive potential, compared to 8.8% in the No Delay group ( = 0.54). VGPR or better response rate did not differ between the Delay and No Delay groups (66.7% vs. 58.8%,  = 0.79). The mean number of lenalidomide prescriptions generated per RVd cycle was 1.35 (range 1-5, SD 0.74).

Conclusions: This study did not demonstrate an effect on clinical response after delays ≥10 days between bortezomib and lenalidomide initiation. No patients in the delay group were females of reproductive potential, which is the primary target for increased safety behind the REMS program.