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Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.
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Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m2) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m2) seem to be preferable.
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ABSTRACT: In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients.
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Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Estadificación de Neoplasias , Resultado del Tratamiento , Adulto JovenRESUMEN
Chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of multiple myeloma (MM) has fundamentally changed the relapsed and refractory therapeutic landscape, but the disease remains incurable. Two CAR-T products, idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti), have been FDA- and EMA-approved for the treatment of relapsed/refractory MM (RRMM); both target B-cell maturation antigen (BCMA), a surface glycoprotein highly expressed on MM cells. Despite deep and durable responses following CAR-T therapy, most patients will need subsequent treatment, and the optimal next-line therapy is presently unclear. Commentary on: Liu et al. Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2. Br J Haematol 2024;204:1780-1789.
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Inmunoterapia Adoptiva , Mieloma Múltiple , Terapia Recuperativa , Humanos , Mieloma Múltiple/terapia , Inmunoterapia Adoptiva/métodos , Terapia Recuperativa/métodos , Antígeno de Maduración de Linfocitos B , Receptores Quiméricos de Antígenos/uso terapéuticoRESUMEN
Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Persona de Mediana Edad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Adulto , Masculino , Femenino , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/etiología , Trasplante Homólogo , Sistema de Registros , Donantes de Tejidos , Donante no EmparentadoRESUMEN
There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the European Society for Blood and Bone Marrow transplantation registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 µmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100 mg/m2 in 23%, 140 mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pretransplant to 66% at day +100 post- ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median estimated glomerular filtration rate increased from 44 to 51 mL/min/1.73 m2. There was no further change between 3 and 12 months post-ASCT. No patient who was RRT-independent at ASCT became RRT dependent by day + 100 post-ASCT. Median follow- up post-ASCT was 84 months (interquartile range [IQR]: 46-122). At 6-years post ASCT, overall survival was 88% (95% confidence interval [CI]: 78-98) and PFS was 44% (95% CI: 28-60). The 2-year cumulative incidence of relapse and non-relapse mortality was 17% (95% CI: 6-27) and 2% (95% CI: 0-6), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI: 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favorable with low non-relapse mortality and good long-term overall survival.
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Trasplante de Células Madre Hematopoyéticas , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , Anciano , Tasa de Filtración Glomerular , Cadenas Ligeras de Inmunoglobulina/sangre , Paraproteinemias/terapia , Paraproteinemias/mortalidad , Paraproteinemias/diagnóstico , Estudios de Seguimiento , Europa (Continente) , Sistema de Registros , Acondicionamiento Pretrasplante/métodosRESUMEN
Recent treatment advancements in multiple myeloma have led to significant improvements in patient outcomes. Maintenance therapy following autologous haematopoietic stem cell transplantation (AHCT) is now standard of care and has been demonstrated to prolong and deepen treatment responses. Currently, lenalidomide remains the single agent that has been approved for maintenance post-AHCT in Europe and the USA which, if tolerated, is continued until disease progression. The treatment landscape is rapidly expanding however, and the optimal personalised maintenance approach for a patient is becoming more complex. Treatment outcomes for patients with high-risk disease remain poor and choice of maintenance in this population also remains unclear. This review article evaluates up-to-date literature regarding established maintenance approaches. It further analyses ongoing studies exploring maintenance regimens using combination and novel agents, approaches to maintenance in patients with cytogenetic high-risk disease and minimal residual disease response-adapted strategies that reflect the current evolving treatment paradigm.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Autólogo , Lenalidomida , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica , Trasplante de Células MadreRESUMEN
Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/diagnóstico , Bortezomib/farmacología , Bortezomib/uso terapéutico , Melfalán/farmacología , Melfalán/uso terapéutico , Estudios Prospectivos , Trasplante Autólogo , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide , Adulto , Humanos , Enfermedad Crónica , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Estudios Retrospectivos , Donante no EmparentadoRESUMEN
Although CMML since long has been separated from MDS, many studies continue to evaluate the outcomes of both diseases after hematopoietic cell transplantation (allo-HCT) together. Data evaluating outcomes of a large CMML cohort after allo-HCT compared to MDS are limited. We aim to compare outcomes of CMML to MDS patients who underwent allo-HCT between 2010 and 2018. Patients ≥18 years with CMML and MDS undergoing allo-HCT reported to the EBMT registry were analyzed. Progression to AML before allo-HCT was an exclusion criterion. Overall survival (OS), progression/relapse-free survival (PFS), relapse incidence (including progression) (REL), and non-relapse mortality (NRM) were evaluated in univariable and multivariable (MVA) Cox proportional hazard models including interaction terms between disease and confounders. In total, 10832 patients who underwent allo-HCT were included in the study, there were a total of 1466 CMML, and 9366 MDS. The median age at time of allo-HCT in CMML (median 60.5, IQR 54.3-65.2 years) was significantly higher than in the MDS cohort (median 58.8, IQR 50.2-64.5 years; p < .001). A significantly higher percentage of CMML patients were male (69.4%) compared to MDS (61.2%; p < .001). There were no clinically meaningful differences in the distribution of Karnofsky score, Sorror HCT-CI score at allo-HCT, and donor type, between the CMML and MDS patients. RIC platforms were utilized in 63.9% of CMML allo-HCT, and in 61.4% of MDS patients (p = .08). In univariable analyses, we found that OS, PFS, and REL were significantly worse in CMML when compared with MDS (all p < .0001), whereas no significant difference was observed in NRM (p = .77). In multivariable analyses, the HR comparing MDS versus CMML for OS was 0.81 (95% CI, 0.74-0.88, p < .001), PFS 0.76 (95% CI 0.70-0.82, p < .001), relapse 0.66 (95% CI 0.59-0.74, p < .001), and NRM 0.87 (95% CI 0.78-0.98, p = .02), respectively. The association between baseline variables and outcome was found to be similar in MDS and CMML (all interaction p > .05) except for a decreasing trend over time of the risk of relapse in CMML (HR allo-HCT per year later 0.94, 95% CI 0.90-0.98), whereas no such trend was observed in MDS (HR 1.00, 95% CI 0.98-1.02). The poor outcome observed for CMML could be related to variables not measured in this study or to factors inherent to the disease itself. This study demonstrates that outcomes of CMML patients after allo-HCT are significantly worse compared to MDS. The results of this study may contribute to future recommendations for allo-HCT in CMML patients.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/métodos , Modelos de Riesgos Proporcionales , Donantes de Tejidos , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodosRESUMEN
Introduction: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma or MALToma) is a prevalent type of primary pulmonary lymphoma. Typically, the primary therapeutic approaches involve surgery or chemotherapy, although there have been instances of radiation therapy being employed. Case Report: We present a case of pulmonary MALToma that exhibited progression despite rituximab therapy. Subsequently, the patient demonstrated a positive response to radiation therapy. Conclusion: This case highlights the potential efficacy of radiation therapy as a treatment option for pulmonary MALToma, especially in cases where other conventional treatments like rituximab have proven ineffective. Further research and studies are warranted to better understand the role of radiation therapy in managing pulmonary MALToma and to determine optimal treatment strategies for patients with this condition.
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In the setting of a first relapse of multiple myeloma (MM), a second autologous stem cell transplant (ASCT) following carfilzomib-lenalidomide-dexamethasone (KRd) is an option, although there is scarce data concerning this approach. We performed a retrospective study involving 22 EBMT-affiliated centers. Eligible MM patients had received a second-line treatment with KRd induction followed by a second ASCT between 2016 and 2018. Primary objective was to estimate progression-free survival (PFS) and overall survival (OS). Secondary objectives were to assess the response rate and identify significant variables affecting PFS and OS. Fifty-one patients were identified, with a median age of 62 years. Median PFS after ASCT was 29.5 months while 24- and 36-months OS rates were 92.1% and 84.5%, respectively. Variables affecting PFS were an interval over four years between transplants and the achievement of a very good partial response (VGPR) or better before the relapse ASCT. Our study suggests that a relapse treatment with ASCT after KRd induction is an effective strategy for patients with a lenalidomide-sensitive first relapse. Patients with at least four years of remission after a frontline ASCT and who achieved at least a VGPR after KRd induction appear to benefit the most from this approach.
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Mieloma Múltiple , Humanos , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Lenalidomida/farmacología , Lenalidomida/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Dexametasona/uso terapéutico , Trasplante AutólogoRESUMEN
In vivo models (mostly rodents) are currently accepted by regulatory authorities for assessing acute inhalation toxicity. Considerable efforts have been made in recent years to evaluate in vitro human airway epithelial models (HAEM) as replacements for in vivo testing. In the current work, an organotypic in vitro rat airway epithelial model (RAEM), rat EpiAirway, was developed and characterized to allow a direct comparison with the available HAEM, human EpiAirway, in order to address potential interspecies variability in responses to harmful agents. The rat and human models were evaluated in 2 independent laboratories with 14 reference chemicals, selected to cover a broad range of chemical structures and reactive groups, as well as known acute animal and human toxicity responses, in 3 replicate rounds of experiments. Toxicity endpoints included changes in tissue viability (MTT assay), epithelial barrier integrity (TEER, transepithelial electrical resistance), and tissue morphology (histopathology). The newly developed rat EpiAirway model produced reproducible results across all replicate experiments in both testing laboratories. Furthermore, a high level of concordance was observed between the RAEM and HAEM toxicity responses (determined by IC25) in both laboratories, with R2=0.78 and 0.88 when analyzed by TEER; and R2=0.92 for both when analyzed by MTT. These results indicate that rat and human airway epithelial tissues respond similarly to acute exposures to chemicals. The new in vitro RAEM will help extrapolate to in vivo rat toxicity responses and support screening as part of a 3Rs program.
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Anemia Refractaria con Exceso de Blastos , Humanos , Ratas , Animales , Sistema Respiratorio , Administración por Inhalación , Epitelio , HemoRESUMEN
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Estudios de Cohortes , Recurrencia Local de Neoplasia , Acondicionamiento Pretrasplante , Melfalán , Trasplante AutólogoRESUMEN
BACKGROUND: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy. METHODS: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib. RESULTS: The median follow-up from maintenance start was 44 months. Three-year progression-free survival (PFS) was 52% (48%-57%) for no EMD, 56% (44%-69%) for paraskeletal involvement, and 45% (22%-68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three-year overall survival (OS) was 81% (77%-84%), 88% (80%-96%), and 68% (47%-89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD. CONCLUSION: Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Bortezomib/uso terapéutico , Lenalidomida/uso terapéutico , Talidomida/uso terapéutico , Autoinjertos , Trasplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéuticoRESUMEN
Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.