Combination therapy with carfilzomib lenalidomide and dexamethasone (KRd) results in an unprecedented purity of the stem cell graft in newly diagnosed patients with myeloma

摘要

Based on available data, most multiple myeloma patients have residual myeloma cells in their autologous hematopoietic progenitor cells (HPC) grafts during collection for autologous stemcell transplant. However, available literature is based on older induction regimens, e.g., adriamycin and dexamethasone (VAD). In that setting, attempts to clean the grafts of residual myeloma cells were unsuccessful and did not improve clinical outcome but rather worsened the recovery of blood counts post-high dose melphalan (HDM) resulting in increased risk of severe post-transplant infections. Recently, the modern carfilzomib, lenalidomide and dexamethasone (KRd) regimen has been developed. KRd shows rapid, deep and durable responses in newly diagnosed myeloma patients reflected in rates of up to 60% minimal residual disease (MRD) negativity when evaluating the individual patient’s bone marrow aspirate. To date, no information is available regarding the use of KRd and its impact on residual myeloma cells in autologous HPC grafts. To expand our knowledge on this topic, we designed a prospective study to compare the patient’s MRD status in the bone marrow with MRD status in the corresponding HPC graft. Furthermore, we were interested in evaluating the yield of HPC in relation to the number of given cycles of KRd combination therapy. Collection of HPC between 4 and 8 completed cycles of KRd had very similar HPC yield. Using MRD assays with sensitivity of 1 × 10⁻⁵ we found that treatment with KRd results in an unprecedented purity of the stem cell graft; specifically, 29 of 30 (97%) patients had an MRD negative graft.