Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 Trial

Abstract

To improve the outcome of allogeneic stem cell transplantation (allo-SCT) in multiple myeloma as part of first-line treatment, we prospectively investigated the feasibility and efficacy of lenalidomide maintenance. Patients started maintenance 1 to 6 months after nonmyeloablative allo-SCT. Lenalidomide was dosed 10 mg on days 1 to 21 of a 28-day schedule for a total of 24 cycles. Peripheral blood samples were taken to evaluate immune modulating effects. Thirtyfive eligible patients were enrolled, and 30 started with lenalidomide. After 2 cycles, 14 patients (47%) had to stop treatment, mainly because of the development of acute graft versus host disease (GVHD). In total, 13 patients (43%) stopped treatment because of development of GVHD, 5 patients (17%) because of other adverse events, and 5 patients (17%) because of progression. Responses improved in 37% of patients, and the estimated 1-year progression-free survival from start of maintenance was 69% (90% confidence interval, 53%-81%). Lenalidomide increased the frequency of human leukocyte antigen-DR ؉ T cells and regulatory T cells, without correlation with clinical parameters. In conclusion, lenalidomide maintenance 10 mg daily after nonmyeloablative allo-SCT with unmanipulated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

“…However, caution is warranted, as the use of lenalidomide as maintenance therapy after allo-SCT might be associated with an unacceptable risk of GvHD [79]. In contrast, the use of bortezomib after RIC allo-SCT in combination with DLI seems to be feasible [80].…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…The HOVON-76 trial assessed LEN maintenance starting 1 to 6 months after allotransplant for newly diagnosed MM. 72 Unfortunately, 53% developed GVHD with 37% acute GVHD (at a median of 18 days on LEN) and 17% cGVHD, leading to premature discontinuation of therapy in 43% of the patients. The study was discontinued early owing to toxicity.…”

“…10%/27% 63%/78% at 18 months 30% aGVHD grades II-IV 47% of all planned cycles completed Most common dose upon completing study 5 mg QOD Kneppers et al 72 Lenalidomide NS/NS 61%/94% at 2 years 37% aGVHD grades II-IV 11% Chronic extensive GVHD Only 10% of patients completed planned therapy Alsina et al 73 Bortezomib 25%/54% 30%/41% at 3 years 25% Grade III aGVHD Caballero-Velazquez et al 78 Bortezomib as part of conditioning 16.9%/NS 74%/77% at 2 years No post transplant maintenance in most patients…”

Pseudo-autologous hematopoietic SCT as treatment for a patient with multiple myeloma who relapsed following an allogeneic hematopoietic SCT

“…The use of lenalidomide as treatment following alloSCT has been reported; 2 however, there was an increased risk of GVHD stimulation. 3 For these reasons, lenalidomide must be used with caution. Eventually, all drug-treatment options fail, for which reason the possibility of using high-dose melphalan for patients who have had long first remissions is an important option to consider.…”