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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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Risk stratification using FLT3 and NPM1 in acute myeloid leukemia patients autografted in first complete remission
Shouval, R., Labopin, M., Bomze, D., Baerlocher, G. M., Capria, S., Blaise, D., Hanel, M., Forcade, E., Huynh, A., Saccardi, R., et al
Bone marrow transplantation. 2020
Abstract
FLT3-ITD and NPM1 mutation refine prognostic stratification in acute myeloid leukemia (AML) with intermediate-risk cytogenetics. However, data on their role in patients undergoing autologous stem cell transplantation (Auto-SCT) as post-remission therapy (PRT) are limited. We therefore sought to retrospectively evaluate the role of FLT3-ITD and NPM1 in a cohort of AML patients (n = 405) with intermediate-risk cytogenetics, autografted in first complete remission (CR1). Patients were transplanted between 2000 and 2014 and reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Leukemia-free survival (LFS) was the primary outcome. Median follow-up was 5.5 years. FLT3-ITD(neg)/NPM1(WT) was the leading molecular subtype (50%), followed by FLT3-ITD(neg)/NPM1(mut) (30%). In the univariate analysis, molecular subtype was associated with LFS, overall survival (OS), and relapse incidence (RI) (p < 0.001); 5-year LFS: FLT3-ITD(neg)/NPM1(mut) 62%, FLT3-ITD(pos)/NPM1(mut) 38%, FLT3-ITD(neg)/NPM1(WT) 32%, and FLT3-ITD(pos)/NPM1(WT) 21%. At 5 years, OS and RI in the FLT3-ITD(neg)/NPM1(mut) subtype were 74% and 35%, respectively. The corresponding OS and RI in other subtypes were below 48% and over 57%. In a Cox multivariable model, molecular subtype was the strongest predictor of LFS, OS, and relapse. In conclusion, AML patients with intermediate-risk cytogenetics and FLT3-ITD(neg)/NPM1(mut) experience favorable outcomes when autografted in CR1, suggesting that Auto-SCT is a valid PRT option.
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[Epidemiology of early infections after autologous hematopoietic stem cell transplantation. Analysis of data from 699 patients treated in a Hungarian centre]
Lakatos, B., Szabo, H., Csordas, K., Tatai, G., Nikolova, R., Csomor, J., Remenyi, P., Masszi, T., Valyi-Nagy, I., Sinko, J.
Orvosi hetilap. 2020;161(3):103-109
Abstract
Introduction: Autologous hemopoietic stem cell transplantation remains a promising therapy in certain malignant and non-malignant conditions. The procedure, however, will increase the risk of complications, most notably early and late infections. Aim: To analyze the frequency and spectrum of pathogens in early (<+100 days) post-transplant infections and to evaluate risk factors for mortality. Method: Prospectively collected data from 699 patients undergoing autologous hemopoietic stem cell transplantation between 2007 and 2014 at our center were retrospectively reviewed and analyzed. Results: The median age of 699 patients was 56 (interquartile range: 43-62) years, 54% (376) were male. 25 patients have been transferred to other centers and 19 patients were lost to follow up. Neutropenic fever occurred in 69.8% (488) of patients. In addition, 102 infectious episodes in 96 patients were identified. Most commonly bacteremia occurred (49 episodes) with a median onset of 7 (5-11) days. The majority (33/49) of bacteremias have been observed during the pre-engraftment period. Their incidence proved to be higher in patients with malignant lymphoma compared to individuals with plasma cell disorders (p = 0.0005, OR: 2.41, 95% CI: 1.49-3.99). 12 episodes of viral infections and 8 cases of proven or probable invasive mycoses have been identified. Among the 655 patients with complete follow up, 16 in-hospital deaths (2.4%) occurred, 8 of them were associated with infections. Survival was adversely affected by early infections (p = 0.0001). Conclusion: In autologous stem cell transplantation, microbiologically unconfirmed neutropenic fever is common. Documented early bacteremia, however, is infrequent. Lymphoma patients have a significantly higher chance to develop bloodstream infections compared to individuals with plasma cell disorders. Early infections decrease the chance of survival; thus, an effective prophylaxis and therapy remains of paramount importance. Orv Hetil. 2020; 161(3): 103-109.
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Tandem autologous stem cell transplantation improves outcome in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the Chronic Malignancies Working Party of EBMT
Gagelmann, N., Eikema, D. J., Koster, L., Caillot, D., Pioltelli, P., Lleonart, J. B., Remenyi, P., Blaise, D., Schaap, N., Trneny, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
Although high-dose therapy and autologous stem cell transplantation combined with novel agents is still the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease and high-risk cytogenetics is not defined yet. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with extramedullary disease undergoing single autologous (n=373), tandem autologous (n=84), or autologous-allogeneic transplantation (n=31) between 2003 and 2015. At least one high-risk abnormality was present in 41% (n=202), with del(17p) (40%) and t(4;14) (45%) being the most frequent. More than one high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival and progression-free survival of 54% and 29% vs. 78% and 49% for standard-risk (p<0.001, respectively). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, overall and progression-free survival were 70% and 43% for single autologous vs. 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (p=0.06 and p=0.30). In multivariate analysis, high-risk cytogenetics were associated with worse survival (HR, 2.00; p=0.003) while tandem autologous significantly improved outcome vs. single autologous transplant (hazard ratios, 0.46 and 0.64; p=0.02 and p=0.03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival while results were limited due to small population (hazard ratio, 0.31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with extramedullary disease and significantly worsens outcome after single autologous while tandem autologous transplant strategy may overcome onset poor prognosis.
PICO Summary
Population
Adult myeloma patients with extramedullary disease (n=488).
Intervention
Tandem autologous transplantation (n=84) or autologous-allogeneic transplantation (n=31)
Comparison
Single autologous transplantation (n=373)
Outcome
Overall and progression-free survival were 70% and 43% for single autologous vs. 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic. In multivariate analysis, high-risk cytogenetics were associated with worse survival, while tandem autologous significantly improved outcome vs. single autologous transplant. Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival while results were limited due to small population.
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[The role of autologous hemopoietic stem cell transplantation in T-cell lymphoma. Hungarian data]. [Hungarian]
Szomor, A., Csalodi, R., Kosztolanyi, S., Nagy, A., Pammer, J., Toth, O., Losonczy, H., Alizadeh, H., Miltenyi, Z., Remenyi, P., et al
Orvosi Hetilap. 2017;158(41):1615-1619
Abstract
T-cell lymphoma is a poor prognostic hematological malignancy. The generally used - not sufficiently effective - induction chemotherapy should be improved with consolidative autologous hemopoetic stem cell transplantation. The authors describe the role, place and effectiveness of transplantation in this disorder. One hundred thirty three autologous stem cell transplantations were performed in the last 22 years in Hungary. Detailed results are available from the last 6 years. In this period 43 transplantations were carried out in 4 Hungarian centers. Carmustine-etoposide-cytosine arabinoside-melphalan (BEAM) conditioning regimen was used in 95%. The transplantation was done mainly in complete remission (84%), 1 year after transplantation 65% of patients were still in complete remission. Eleven patients died, 82% of them have progressive disease. Brentuximab vedotin has already proved the effectiveness, several other chemoterapeutics, monoclonal antibodies, kinase inhibitors are under investigation. In certain cases allogeneic stem cell transplantation has real indication among therapeutic options. Orv Hetil. 2017; 158(41): 1615-1619.
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Early Versus Delayed Autologous Stem Cell Transplantation and Interferon Maintenance in Multiple Myeloma: Single-Center Experience of 18 Years
Remenyi, P., Varga, G., Mikala, G., Reti, M., Gopcsa, L., Batai, A., Csukly, Z., Lengyel, L., Torbagyi, E., Barta, A., et al
Transplantation Proceedings. 2016;48(1):177-84
Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) has become the mainstay of 1st-line treatment in younger patients with multiple myeloma (MM), but statistical confirmation of its superiority over other therapies, especially in the era of novel agents, is still lacking. METHODS We reviewed the results of all 548 myeloma ASCTs performed in our institute over the past 18 years. RESULTS More than one-half of the patients had access to novel agents before their transplantations. Although the age of the transplanted patients increased significantly over the years, treatment-related mortality (TRM) was remarkably low, especially in 1st-line transplanted patients (100-day TRM, 0.3%). The median overall survival (OS) of the entire cohort was 98.4 months. Patients transplanted within 12 months from the start of their therapy had significantly better responses than those having delayed ASCT (complete response rate, 58.1% vs 46.8%; P = .016) and significant post-ASCT progression-free survival (PFS) benefit (30.2 [26.1-34.3] mo vs 23.3 [16.8-29.8] mo; P = .036), but we found no significant overall survival difference. The results were similar in patients treated with or without novel agents before ASCT. During a period of time, interferon maintenance was our standard approach to post-ASCT maintenance. Our analysis showed not only a significant PFS advantage with interferon, but also a highly significant overall survival benefit (150.4 [105.1-195.8] mo vs 86.1 [72.5-99.7] mo; P = .003). CONCLUSIONS Our findings demonstrate that delayed ASCT can be feasible in selected patients. Copyright © 2016 Elsevier Inc. All rights reserved.