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Prognostic impact of early-versus-late responses to different induction regimens in patients with myeloma undergoing autologous hematopoietic cell transplantation: results from the CALM study by the CMWP of the EBMT
Garderet, L., Sbianchi, G., Iacobelli, S., Blaise, D., Byrne, J. L., Remenyi, P., Apperley, J. F., Touzeau, C., Isaksson, C., Browne, P., et al
European journal of haematology. 2021
Abstract
BACKGROUND In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. METHOD We analysed 1,222 ASCT patients who were classified based on (1) the interval between induction and stem cell collection, (2) the type of induction regimen: BID (Bortezomib, IMiDs and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide and Dexamethasone), and (3) the time to best response (Early i.e. best response within 4 or 5 months, depending on the regimen vs Late; Good i.e. VGPR or better vs Poor) RESULTS The length of induction treatment required to achieve a Good response did not affect PFS (p=0.65) or OS (p=0.61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (p=0.31), and median OS 81.7, 92.7, and 77.4 months, respectively (p=0.83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, p value = 0.02). However, achieving a Good response at induction was associated with a better response (= VGPR) post-transplant CONCLUSION The kinetics of response did not affect outcomes.
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Long-acting granulocyte colony-stimulating factor pegfilgrastim (lipegfilgrastim) for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation
Danylesko, I., Sareli, R., Varda-Bloom, N., Yerushalmi, R., Shem-Tov, N., Magen, H., Shimoni, A., Nagler, A.
International journal of hematology. 2021
Abstract
Autologous stem cell transplantation (ASCT) is a standard of care in newly-diagnosed multiple myeloma (MM) patients. Several studies before the introduction of novel therapies in MM, demonstrated a pegylated G-CSF to be successful in mobilizing peripheral blood stem cells (PBSCs). Lipegfilgrastim is a novel long-acting G-CSF that is produced by the conjugation of a single 20-kDa polyethelene glycol to the natural O-glycosylation site of G-CSF. Twenty-four MM patients were included for PBSCs mobilization with a single SC injection of 6 mg lipegfilgrastim. PBSC collection was started when the CD34(+) count was > 10 × 10(6) cells/L. The target progenitor cells were 6 × 10(6) cells/kg. The median day of apheresis was + 3 (range 2-5) following lipegfilgrastim. Median peripheral blood CD34(+) count pre-mobilization was of 22.65 (range 3.36-105) × 10(6) cells/L. The median number of leukaphaeresis procedures was 2 (range 1-4). The median mobilized CD34(+) cells/kg were 8.26 (range 0.77-12.42). One patient failed to mobilize and two patients mobilized < 6 × 10(6) cells/kg. Toxicity was mild and transient. Twenty-three patients underwent ASCT following high dose melphalan. All patients engrafted. As lipegfilgrastim is administered only once, it is conceivable that it improves both compliance and quality-of-life (NCT02488382).
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Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis
Pasvolsky, O., Yeshurun, M., Fraser, R., Estrada-Merly, N., Rozovski, U., Shargian-Alon, L., Assal, A., Banerjee, R., Bumma, N., Gale, R. P., et al
Bone marrow transplantation. 2021
Abstract
The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p?0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p?0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p?0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p?0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p?=?0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.
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LDH and renal function are prognostic factors for long-term outcomes of multiple myeloma patients undergoing allogeneic hematopoietic stem cell
Shouval, R., Teper, O., Fein, J. A., Danylesko, I., Shem Tov, N., Yerushalmi, R., Avigdor, A., Vasilev, E., Magen, H., Nagler, A., et al
Bone marrow transplantation. 2020
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-SCT) may offer a cure for selected patients with multiple myeloma (MM). Effective prognostic markers to guide patient selection are warranted. We retrospectively studied a cohort of 100 relapsed refractory MM patients who underwent allo-SCT. With a median follow-up of 12.2 years, median overall survival (OS) and progression-free survival (LFS) were 9.2 months and 5.6 months, respectively. 5-years OS and PFS were was 18.0% and 16.8%. The cumulative incidence of 5-years relapse was 45.9% and non-relapse mortality (NRM) 36.0%. In a multivariable Cox model, decreasing albumin, increasing lactate dehydrogenase (LDH), advanced disease, and mismatched donors were predictive of both reduced OS and PFS. The probability of 5-years OS was higher in patients with LDH below vs. the upper limit of normal (22% vs. 5%, p = 0.004). In the multivariable analysis, the hazard of NRM was increased with low albumin, mismatched donor type, and declining estimated glomerular filtration rate (eGFR). Patients with a low eGFR had a 5-year NRM incidence of 31% vs. 56% in patients with higher levels (p = 0.02). Graft-versus-host disease was not associated with improved outcomes. In conclusion, LDH, renal function, and albumin are highly informative of outcomes in MM patients treated with allo-SCT.
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5.
Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response
Mina, R., Petrucci, M. T., Corradini, P., Spada, S., Patriarca, F., Cerrato, C., De Paoli, L., Pescosta, N., Ria, R., Malfitano, A., et al
Clinical lymphoma, myeloma & leukemia. 2018
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Editor's Choice
Abstract
BACKGROUND High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy. PATIENTS AND METHODS We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m). RESULTS Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy. CONCLUSION Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.
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Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis
Gay, F., Oliva, S., Petrucci, M. T., Montefusco, V., Conticello, C., Musto, P., Catalano, L., Evangelista, A., Spada, S., Campbell, P., et al
Leukemia. 2017;31(8):1727-1734
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Abstract
In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200mg/m2and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.
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Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide-dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis
Leiba, M., Kedmi, M., Duek, A., Freidman, T., Weiss, M., Leiba, R., Nagler, A., Avigdor, A.
British Journal of Haematology. 2014;166(5):702-10
Abstract
Three-drug induction regimens have become the standard of care in newly diagnosed transplant-eligible multiple myeloma patients. Two frequently used protocols are bortezomib, cyclophosphamide and dexamethasone (VCD) and bortezomib, thalidomide and dexamethasone (VTD). Comparisons between the two are lacking. The present study aimed to identify the differences in response rate and toxicity between the two regimens. Databases were searched using the terms 'VTD' or 'VCD' and 'induction regimens for newly diagnosed multiple myeloma'. Prospective trials evaluating initial response in transplant eligible patients were included. The main outcome measures were response rates and adverse events. Eight clinical trials were eligible for analysis. Overall 672 patients were treated with either VCD (n = 157) or VTD (n = 515) as induction therapy. Patients treated with VTD presented with a significantly higher complete/near complete response (34% vs. 6%, P = 0·002) as well as a higher very good partial response rate or better, following induction therapy (62% vs. 27%, P < 0·0001). Although grade 3-4 neurotoxicity was more frequent during VTD therapy (11% vs. 6%, P = 0·057), a higher incidence of overall grade 3-4 adverse events was found in the VCD-treated patients (74% vs. 51%, P < 0·001). VTD induction therapy may be superior in achieving deeper response rate following induction therapy, and is better tolerated.