Keywords
How to Cite
Abstract
Introduction: the objective of first-line treatment in patients with MM who are candidates for autologous hematopoietic transplantation (HSCT) is to achieve the greatest possible depth of response, which has prolonged survival in this group of patients (pts).
Different induction schemes are available prior to HSCT. Currently, the RVd scheme one of the best recommended options according to different treatment guidelines. There are no published data on the efficacy and safety of RVd as an induction regimen in Latin America in real word evidence studies.
Objectives: our primary objective was to describe the efficacy of RVd as induction prior to HSCT.
In addition, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated.
Material and methods: retrospective, multicenter study of 13 centers belonging to the GAMM. Adult pts with newly diagnosed MM candidates for HSCT treated with RVd between April 2016 and April 2021 were included. Response rates were analyzed according to IMWG-2016 criteria and toxicities according to CTCAE V4.3.
Results: 110 pts with a median age of 58 years (range 29-71) with 50% female subjects and a median follow-up of 17 months were included. 29 pts (27%) presented R-ISS 3, 21 pts (19%) high cytogenetic risk and 11 pts (10%) extramedullary disease.
The median number of RVd cycles received was 6 (range 2-10). 15 pts (14%) required plerixafor prior to stem cell collection and 14 pts (13%) failed initial mobilization. The median number of CD34+ cells per kg was 4.6 x 106 (IQR 3.21-6.14). Response rates prior to HSCT were: 97% overall response rate (ORR), 77% very good partial response (VGPR) or greater and 40% complete response (CR). The CR rate was similar between patients with high cytogenetic risk vs. standard risk (p:0.39). Post-HSCT response rates were: 99% ORR, 93% VGPR or greater and 75% CR. The most frequent adverse events of any grade were: hematological (42%), infectious (39%), gastrointestinal (29%) and peripheral neuropathy (23%). The PFS at 24 months was 88% for the entire cohort (95% CI 75-94). In those pts who achieved CR prior to HSCT, the PFS at 24 months was 100% vs 80% in the rest (p: 0.005). The OS at 24 months is 95% (95% CI 87-98).
Conclusions: in our cohort outside of a clinical trial, RVd turned out to be an effective regimen with an adequate safety profile. The HSCT further deepened response rates. This is the first experience of the use of RVd as induction prior to HSCT in Latin America.
Objectives: Our primary objective was to describe the efficacy of RVd as induction prior to HSCT. In addition, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated.
Material and methods: retrospective, multicenter study of 13centers belonging to the GAMM. Adult pts with newly diagnosed MM candidates for HSCT treated with RVd between April 2016 and April 2021 were included. Response rates were analyzed according to IMWG-2016 criteria and toxicities according to CTCAE V4.3
Results: 110 pts with a median age of 58 years (range 29-71) with 50% female subjects and a median follow-up of 17 months were included. 29 pts (27%) presented R-ISS 3, 21 pts (19%) high cytogenetic risk and 11 pts (10%) extramedullary disease. The median number of RVd cycles received was 6 (range 2-10). 15 pts (14%) required plerixafor prior to stem cell collection and 14 pts (13%) failed initial mobilization. The median number of CD34+ cells per kg was 4.6 x106 (IQR 3.21-6.14). Response rates prior to HSCT were: 97% overall response rate (ORR), 77% very good partial response (VGPR) or greater, and 40% complete response (CR). The CR rate was similar between patients with high cytogenetic risk vs. standard risk (p:0.39). Post-HSCT response rates were: 99% ORR, 93% VGPR or greater, and 75% CR. The most frequent adverse events of any grade were: hematological (42%), infectious (39%), gastrointestinal (29%) and peripheral neuropathy (23%). The PFS at 24 months was 88% for the entire cohort (95% CI 75-94). In those pts who achieved CR prior to HSCT, the PFS at 24 months was 100% vs 80% in the rest (p: 0.005). The OS at 24 months is 95% (95% CI 87-98).
Conclusions: In our cohort outside of a clinical trial, RVd turned out to be an effective regimen with an adequate safety profile. The HSCT further deepened response rates. This is the first experience of the use of RVd as induction prior to HSCT in Latin America.
References
Usmani SZ, Hoering A, Cavo M, et al. Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma - an IMWG research project. Blood Cancer J. 2018;8(12):123.
Perrot A. How I treat frontline transplantation-eligible multiple myeloma. Blood 2022; 139(19):2882-2888.
Costa L, Usmani S. Defining and managing High risk Multiple Myeloma. Current concepts. J Natl Compr Canc Netw 2020; 18(12): 1726-1730.
Davies F, Pawlyn Ch, Usmani S et al. Perspectives on the risk stratified treatment of multiple myeloma. Blood Cancer Discov 2022; 3: 1-12.
Mikhael J, Ismaila N, Cheung M et al. Treatment of multiple myeloma: ASCO and CCO Joint Clinical Practice Guideline. J Clin Oncol 2019; 37 (14): 1228-1263.
Dimopoulos MA, Moreau P, Terpos E, et al. Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up. Ann Oncol 2021; 32 (39): 309-322.
Callender NS, Baljevic M, Adekola K, et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2022. J Natl Compr Canc Netw 2022; 20(1): 8-19.
Rosiñol L, Oriol A, Rios R, Sureda A, Blanchard MJ, Hernández MT, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood 2019;134 (16):1337–45.
Perrot A, Lauwers-Cances V, Cazaubiel T, Facon T, Caillot D, Clement-Filliatre L,
et al. Early versus late autologous stem cell transplant in newly diagnosed multiple
myeloma: long-term follow-up analysis of the IFM 2009 trial. Blood 2020; 136:39.
Richardson PG, Jacobus SJ, Weller EA, et al. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMoa2204925. Online ahead of print.
Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol 2015; 33: 2863-2869.
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17(8): 328-346.
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010). https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
Sidana S, Kumar S, Fraser R, et al. Impact of Induction Therapy with VRD versus VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation. Transplant Cell Ther 2022 (28): 83.e1-83.e9.
Afrough A, Pasvolsky O, Ma J, et al. Impact of Induction With VCD Versus VRD on the Outcome of Patients With Multiple Myeloma After an Autologous Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2022 Jun;28(6): 307.e1-307.e8.
Schutz N, Ochoa P, Duarte P, et al. Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple. Hematol Oncol 2020; 38(3):363-371.
Gay F, Musto P, Rota-Scalabrini D, Bertamini L, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol. 2021;22:1705–1720.
Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38.
Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945.
Sonneveld P, Broijl A, Gay F, et al. Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): a multicenter, randomized, phase III study (PERSEUS). J Clin Oncol. 2019;37: TPS8055–TPS.
Landgren O, Hultcrantz M, Diamond B, et al. Safety and effectiveness of weekly carfilzomib, lenalidomide, dexamethasone, and daratumumab combination therapy for patients with newly diagnosed multiple myeloma: the MANHATTAN nonrandomized clinical trial. JAMA Oncol. 2021;7(6):862-868.
Goldschmidt H, Mai EK, Nievergall E, et al. Addition of isatuximab to lenalidomide, bortezomib and dexamethasone as induction therapy for newly-diagnosed, transplant-eligible multiple myeloma patients: the phase III GMMG-HD7 trial. Blood. 2021; 138:463.
Leypoldt LB, Besemer B, Asemissen AM, et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG CONCEPT
trial. Leukemia. 2022; 36(3):885–888.
Goldschmidt H, Mai EK, Bertsch U, et al. Elotuzumab in combination with lenalidomide, bortezomib, dexamethasone and autologous transplantation for newly-diagnosed multiple myeloma: results from the randomized phase III GMMG-HD6 trial. Blood. 2021; 138:486.
All material published in the journal HEMATOLOGÍA (electronic and print version) is transferred to the Argentinean Society of Hematology. In accordance with the copyright Act (Act 11 723), a copyright transfer form will be sent to the authors of approved works, which has to be signed by all the authors before its publication. Authors should keep a copy of the original since the journal is not responsible for damages or losses of the material that was submitted. Authors should send an electronic version to the email: revista@sah.org.ar