RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group

Abstract

Autologous stem cell transplantation (ASCT) combined with novel agents is the standard treatment for transplant-eligible, newly diagnosed myeloma (NDMM) patients. Lenalidomide is approved for maintenance after ASCT until progression, although the optimal duration of maintenance is unknown. In this trial, 80 patients with NDMM received three cycles of lenalidomide, bortezomib, and dexamethasone followed by ASCT and lenalidomide maintenance until progression or toxicity. The primary endpoint was the proportion of flow-negative patients. Molecular response was assessed if patients were flow-negative or in stringent complete response (sCR). By intention to treat, the overall response rate was 89%. Neither median progression-free survival nor overall survival (OS) has been reached. The OS at 3 years was 83%. Flow-negativity was reached in 53% and PCR-negativity in 28% of the patients. With a median follow-up of 27 months, 29 (36%) patients are still on lenalidomide and 66% of them have sustained flow-negativity. Lenalidomide maintenance phase was reached in 8/16 high-risk patients but seven of them have progressed after a median of only 6 months. In low- or standard-risk patients, the outcome was promising, but high-risk patients need more effective treatment approach. Flow-negativity with the conventional flow was an independent predictor for longer PFS.Electronic supplementary materialThe online version of this article (10.1007/s00277-019-03815-7) contains supplementary material, which is available to authorized users.

Autograft cellular composition and outcome in myeloma patients: Results of the prospective multicenter GOA study

“…The patients received their first auto‐SCT between May 2012 and December 2016 at four university hospitals (Kuopio, Oulu, Tampere, and Turku) in Finland. A proportion of the patients ( n = 36, 28%) participated also in the MM‐02 study (NCT01790737) conducted by the Finnish Myeloma Group 16,17 …”

“…The G‐CSF mobilized patients received filgrastim of 10 μg/kg daily until the completion of cell apheresis. The subgroup of patients participating in the MM02 trial received mobilization with either LD‐CY plus filgrastim or filgrastim alone in a randomized fashion after three cycles of induction treatment with bortezomib, lenalidomide and dexamethasone (VRD) followed by a single auto‐SCT and lenalidomide maintenance 16,17 . The blood CD34 + (B‐CD34 + ) level was determined daily during the stem cell collection period by flow cytometry using an ISHAGE protocol 19 at the stem cell laboratories of each participating university hospital.…”

Comparison of CD34+ cell mobilization, blood graft cellular composition, and post‐transplant outcome in myeloma patients mobilized with filgrastim or pegfilgrastim added to low‐dose cyclophosphamide: A prospective multicenter study

“…A total of 70 patients received filgrastim (FIL) 5 μg/kg until the completion of apheresis and 20 patients received a single dose of pegfilgrastim (PEG) 6 mg as a G‐CSF in the mobilization according to the institutional standards of care thus forming the groups of the present study. Earlier after the diagnosis, 19 patients in the present study had also been enrolled in the MM‐02 study of the Finnish Myeloma Group 14,15 . Altogether 35 patients (50%) in the FIL group and four patients (20%) in the PEG group had received lenalidomide (LEN) as a part of induction therapy (p < .001).…”

Minimal Residual Disease in Multiple Myeloma: State of the Art and Applications in Clinical Practice

“…Meta-analysis was done on four previous studies, and found statistically significant difference regarding PFS and OS between patients who had achieved MRD negativity and those who had not [74]. Other analyzed data from 14 studies confirmed MRD negativity with statistical significance as surrogate for PFS and OS [70].…”

“…Flow-measured MRD was a primary endpoint in a study in which MM patients were treated with lenalidomide, Velcade, and dexamethasone (RVd) at diagnosis, followed by autologous stem cell transplantation and R maintenance [ 70 ]. ORR was 89% with 53% flow MRD-negative patients, half of which were negative by PCR.…”