Background: The results of international randomized clinical trials emphasize the expediency of maintenance therapy following auto-HSCT. However, these studies did not assess such important issues as the need for maintenance therapy in patients who have achieved complete remission (CR) or stringent CR following auto-HSCT. Probably, the results of studying MRD following auto-HSCT will allow receiving a substantiated answer to this question.
Aims: To evaluate the efficacy of maintenance therapy following auto-HSCT depending on MRD in patients with multiple myeloma.
Patients and methods: Over the period from January 2012 to April 2018, 70 MM patients (24 males and 46 females) aged 32 to 65 years (median=56) were enrolled into a prospective study. The disease stage according to the International Staging System (ISS) was I, II and III in 28, 19 and 23 patients, respectively. All patients received induction therapy with bortezomib; immunomodulatory drugs were used in 10 cases. After the induction therapy, a single and tandem auto-HSCT were performed in 57 and 13 patients, respectively. On Day 100 following auto-HSCT, bone marrow examination was carried out in order to determine MRD using six-color flow cytometry with a panel of antigens: CD38, CD138, CD45, CD56, CD117, CD19. MRD-negative status was diagnosed in case of detection of <20 clonal plasma cells among 2,000,000 white blood cells (<0.001%; detection limit 10-5). On Day 100 after the auto-HSCT, all patients achieved CR of the disease and were randomized to receive maintenance therapy with lenalidomide 15 mg/day from Day 1 to Day 21 of a 28-day course within a year or no such therapy. The follow-up period since the moment of MRD determination was 2-28 months (median 15). Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10.
Results: 37 patients were randomized to receive maintenance therapy with lenalidomide following auto-HSCT, including 23 patients in whom plasma cell immunophenotyping showed the lack of MRD and 14 patients in whom MRD-positive status was confirmed. Thirty-three patients were followed-up without further treatment after the auto-HSCT, including 24 cases with MRD-negative status and 9 cases with the presence of abnormal plasma cells in the bone marrow. The compared groups were comparable in respect of such parameters as age and the ISS stage.
The differences between two-year PFS rates in MM patients with MRD-negative status following auto-HSCT who received (n=23) or didn't receive (n=24) the maintenance therapy, showed no statistical significance (p=0.3) and were 88% and 74%, respectively (Fig.1a). In patients with MRD-positive status following auto-HSCT who received lenalidomide, two-year PFS rate was significantly (p<0.05) higher and was 92% versus 45% in the group of patients who didn't receive the maintenance therapy (Fig.1b).
Conclusion: Achievement of MRD-negative status following auto-HSCT was accompanied by high values of PFS regardless of the use or not use the maintenance therapy with lenalidomide (88% versus 74%, p=0.3). Prescription of the maintenance therapy to patients with MRD-positive status following auto-HSCT improves the PFS.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.