Abstract
Background
Lenalidomide, bortezomib, and dexamethasone induction chemotherapy (RVd) followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is a third-generation immunomodulatory drug currently approved for relapsed-refractory multiple myeloma. Data on the use of Pomalidomide in NDMM is limited.
Methods
This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) induction for NDMM. The study included transplant-eligible and ineligible patients from age 18-75years with ECOG performance status 0-2. The patients received four cycles of PVd induction followed by response assessment as per the International Myeloma Working Group (IMWG) criteria. PET/CT was performed in all patients at baseline and after 4 cycles. Transplant-eligible patients proceeded for ASCT after 4-6cycles followed by maintenance. Transplant ineligible patients continued the chemotherapy for nine cycles, followed by maintenance. Primary endpoint was estimation of patients achieving very good partial response and better (≥VGPR) after four cycles. Secondary endpoints were assessment of safety, progression free survival (PFS) and overall survival (OS)
Results
We report the results of the first stage of the phase 2 trial, which was stopped as the proposed endpoint was achieved. Median duration of follow-up was 14months. Thirty-four patients were included in the study. Two patients developed serious adverse events (AEs) and one was lost to followup. Thirty-one patients completed all four induction cycles. The median age was 52years (32-72), and males were 17 (51%). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had International staging system (ISS) stage-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Four patients had high-risk cytogenetic abnormalities [as defined by Del 17p, t(4,14), t(11,14), t(14,16)]. After four cycles of PVd induction, 19 (61%) had complete response and better (≥CR), 27 (87%) had ≥VGPR, and 4 (13%) patients had partial response (PR). Fifteen (48%) had a complete metabolic response (CMR) on PET/CT. ASCT was performed on 11 patients. Pomalidomide did not interfere with stem cell harvest.
PVd showed manageable toxicity profile. Anemia (21%) was the most common hematological toxicity of any grade. Peripheral neuropathy (27%), fatigue (27%), and constipation (24%) were the most common non-hematological toxicities of any grade. Two patients developed SAEs.
Patients with ≥VGPR had significantly better 12month PFS than those with PR. Patients with ≥VGPR and CMR on PET/CT had significantly better 12month OS.
Conclusion
Induction chemotherapy using the PVd regimen is safe and efficacious in NDMM. Further Phase 3 studies with longer follow-up are necessary to establish the superiority and survival benefit over the conventional regimens.
Disclosures
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
