1.
Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching
Moreau, P., Hulin, C., Zweegman, S., Hashim, M., Hu, Y., Heeg, B., de Boer, C., Vanquickelberghe, V., Kampfenkel, T., He, J., et al
EJHaem. 2021;2(1):66-80
Abstract
BACKGROUND Traditional bortezomib, thalidomide, and dexamethasone (VTd) regimens for patients with newly diagnosed multiple myeloma (NDMM) include doses of thalidomide up to 200 mg/day (VTd-label). Clinical practice has evolved to use a lower dose (100 mg/day) to reduce toxicity (VTd-mod), which was evaluated in the phase III CASSIOPEIA study, without or with daratumumab (D-VTd; an anti-CD38 monoclonal antibody). We used propensity score matching to compare efficacy and safety for VTd-mod and D-VTd with VTd-label. METHODS Patient-level data for VTd-mod and D-VTd from CASSIOPEIA (NCT02541383) and data for VTd-label from the PETHEMA/GEM study (NCT00461747) were analyzed. Propensity scores were estimated using logistic regression, and nearest-neighbor matching procedure was used. Outcomes included overall survival (OS), progression-free survival (PFS), time to progression (TTP), postinduction and posttransplant responses, as well as rate of treatment discontinuation and grade 3/4 peripheral neuropathy. RESULTS VTd-mod was noninferior to VTd-label for OS, PFS, TTP, postinduction very good partial response or better (≥VGPR) and overall response rate (ORR). VTd-mod was significantly better for posttransplant ≥VGPR and ORR versus VTd-label. VTd-mod safety was not superior to VTd-label despite the lower thalidomide dose. D-VTd was significantly better than VTd-label for OS, PFS, TTP, postinduction and posttransplant ≥VGPR and ORR, and was noninferior to VTd-label for safety outcomes. CONCLUSIONS In transplant-eligible patients with NDMM, D-VTd had superior efficacy compared with VTd-label. Despite a lower dose of thalidomide, VTd-mod was noninferior to VTd-label for safety and was significantly better for posttransplant ≥VGPR/ORR. These data further support the first-line use of daratumumab plus VTd.
2.
Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017
Yin, X., Tang, L., Fan, F., Jiang, Q., Sun, C., Hu, Y.
Cancer cell international. 2018;18:62
Abstract
Background: Despite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT. Patients/methods: We systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords 'allogeneic' and 'myeloma'. Results: A total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56-84%), 62 (95% CI 53-71%), 52 (95% CI 44-61%), and 46 (95% CI 40-52%), respectively; for progression-free survival were 51 (95% CI 38-64%), 40 (95% CI 32-48%), 34 (95% CI 27-41%), and 27 (95% CI 23-31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14-21%), 21 (95% CI 17-25%), 20 (95% CI 13-26%), and 27 (95% CI 21-33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5-18%). The incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30-37%) and 51 (95% CI 46-56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45-55%) and 51 (95% CI 45-57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk. Conclusion: Due to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options.