Abstract
Introduction
Multiple myeloma (MM) represents an incurable plasma cell malignancy. Success in the management of this disease requires a focus on prolonging disease control to positively impact survival. This is the rationale behind maintenance chemotherapy after frontline autologous stem cell transplant (ASCT). Recent large-scale phase 3 randomized trials have shown daily low dose lenalidomide, an oral immunomodulator (IMID), has led to markedly improved progression free survival (PFS) and an evolving benefit on overall survival (OS). We sought to evaluate the effect of lenalidomide maintenance in patients with MM undergoing bortezomib-based induction chemotherapy and ASCT in a real world setting.
Methods
Retrospective review of patients with MM undergoing initial bortezomib-based induction chemotherapy and ASCT was completed in patients at our institution. Patients who began therapy up until June 30th, 2015 were included to ensure a minimum of 2-yrs follow-up. Patients were analyzed on an intention-to-treat basis. Maintenance chemotherapy included those on lenalidomide alone or lenalidomide plus bortezomib, the latter being a treatment option at our centre for high-risk patients. OS was measured from the time induction therapy was started until death or last follow-up. PFS was measured from the time of induction therapy initiation to relapse, death or last follow-up. Maximal response to treatment was assessed according to the IMWG consensus criteria although an additional endpoint of near CR (nCR) was included to account for patients where the monoclonal protein on electrophoresis disappeared and light chains normalized but where CR was not confirmed with immunofixation and a bone marrow biopsy was not done.
Results
198 patients were included in the analysis. 121 received lenalidomide based maintenance and 77 received no maintenance between December 2004 to June 30th, 2015. Median ISS score was 2 in both groups without significant difference between them (p=0.98) . In the maintenance and no maintenance groups respectively 32% and 36% had ISS stage 3 disease. The mean number of maintenance cycles received was 25 cycles (0.5 - 84). Sixty percent of patients required dose reductions or discontinuation due to adverse effects excluding relapse. Most commonly this was due to cytopenias (29.8%), rash (10.7%), infection (9.1%) and fatigue (5.8%). 15% discontinued therapy before relapse occurred. Though venous thromboembolism and second primary malignancies (SPMs) are a worry in patients treated long term with IMIDs these were only seen in 3.3% and 1.7% of patients respectively. Median follow-up in the maintenance group was 44 months and 60 months in the no maintenance group. Survival data is shown in figure 1. The median OS was not reached in the maintenance cohort and was 89 months in the no maintenance group (p = 0.01). Estimated 3-year OS was superior in the maintenance group at 88.4% versus 80.5% in the no maintenance cohort. A statistically significant difference in median PFS was also noted favouring the lenalidomide maintenance (55.0 months versus 32.9 months, p=0.002). Of patients treated with lenalidomide-based maintenance 95.0% achieved ≥ VGPR (53.7% ≥ nCR) while 77.9% (29.1% ≥ nCR) of those who did not receive maintenance therapy achieved these endpoints (p=0.03). Further characterization of therapy for relapsed disease as well as PFS after 1st relapse (2nd PFS) and time to second relapse (PFS2) will be presented at the meeting.
Conclusions
Our retrospective analysis of lenalidomide maintenance therapy in MM patients treated with bortezomib-based induction chemotherapy and ASCT illustrates the positive impact lenalidomide has had on both PFS and OS. Patients treated with lenalidomide at our centre experienced a more prolonged and profound remission of their disease. The treatment was well tolerated with no unexpected adverse effects. Rates of thromboembolic disease and SPMs were low. Most importantly, the superior OS in the maintenance arm suggests that second line therapy for those not receiving maintenance could not overcome the negative impact of an earlier relapse. This data supports our ongoing approach incorporating lenalidomide-based maintenance continued until progression for all patients who have undergone an ASCT. Importantly, these real world results validate the phase 3 trial experience, helping to further establish this approach as a standard of care.
Belch: Amgen, Celgene, Takeda: Honoraria.
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