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1.
In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT
Beksac, M., Eikema, D. J., Koster, L., Hulin, C., Poiré, X., Hamladji, R. M., Gromek, T., Bazarbachi, A., Ozkurt, Z. N., Pabst, T., et al
Bone marrow transplantation. 2024
Abstract
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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2.
Efficacy of autologous stem cell transplantation for patients with myeloma having suboptimal response: A multicenter retrospective analysis
Suzuki, K., Shimazu, Y., Minakata, D., Ikeda, T., Takahashi, H., Tsukada, N., Kanda, Y., Doki, N., Nishiwaki, K., Miwa, A., et al
Transplantation and cellular therapy. 2023
Abstract
Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients when partial response (PR) or better is achieved after induction therapy. However, its clinical significance in patients with suboptimal response (SR), including stable disease (SD) and progressive disease (PD) before ASCT, has not been established. Additionally, functional high-risk (FHR), including RS and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients having SR in novel agent era. This multicenter, retrospective study was conducted using the Transplant Registry Unified Management Program (TRUMP) database of the Japanese Society of Transplantation and Cellular Therapy (JSTCT) and included 3898 patients with transplant-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7% including 1.7% of PD. In survival time analysis for overall cases, The significant difference of PFS between the VGPR and PR groups were observed while there was no significant difference of OS between the VGPR and PR groups. Additionally, there was no significant difference of OS and PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median age of the patients was 60 years (range, 30-77 years). In total, 1605 (97.4%), 561 (38.2%), and 512 (34.9%) patients received bortezomib, immunomodulatory drug (IMiD), and both bortezomib and IMiD, respectively. A total of 558 (38.0%) patients received reinduction therapy. There were 229 (37.7 %) patients with high-risk cytogenetic risk (HRCA). In a median follow-up period of 31.7 months, a significant difference was observed in 30-month overall survival (OS) rates between the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; p <0.001). In a comparison between the PR and SD groups, the OS in the SD group was significantly shorter than that in the PR among the patients with HRCA (p <0.001) and in the patients treated with reinduction therapy (p = 0.013). Concerning the PD group, the 30-month OS and PFS rates in the PD group were 39.4% and 17.9%. Finally, early PD within 12 months after ASCT predicted short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, the OS in the SR was not always short, but the SR in the HRCA and the reinduction therapy groups predicted to short OS so that alternative therapeutic options to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcome when early PD was not occurred even in the PD group.
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3.
Amplification of Chromosome 1q Predicts Poor Overall Survival in Newly Diagnosed Multiple Myeloma Patients
Skerget, M., Skopec, B., Zver, S., Podgornik, H.
Journal of hematology. 2023;12(3):109-113
Abstract
BACKGROUND Chromosome 1q copy number alterations are common in newly diagnosed patients with multiple myeloma, and in most published studies, there is no distinction made between three copies or the addition of at least four copies. The impact of these copy number alterations on patient outcome and optimal treatment is not fully understood. METHODS We retrospectively analyzed 136 transplant eligible patients with newly diagnosed multiple myeloma from our national registry, who were treated with first autologous stem cell transplantation (aHSCT) between January 1, 2018, and December 31, 2021. The primary endpoint was overall survival. RESULTS Patients with at least four copies of chromosome 1q had the poorest prognosis, with an overall survival of only 28.3 months. In multivariate analysis, four copies of chromosome 1q were the only statistically significant factor for overall survival. CONCLUSIONS Despite the use of novel agents, transplantation, and maintenance therapy, patients with a gain of four copies of chromosome 1q have a very poor survival rate. Therefore, prospective studies using immunotherapy in this patient population are necessary.
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4.
Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019
Swan, D., Hayden, P. J., Eikema, D. J., Koster, L., Sauer, S., Blaise, D., Nicholson, E., Rabin, N., Touzeau, C., Byrne, J., et al
British journal of haematology. 2022
Abstract
Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy-based induction fell significantly, being largely replaced by bortezomib-based regimens. The two-year complete response rate increased from 22% to 42%. The five-year progression-free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
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5.
Improved survival of multiple myeloma patients treated with autologous transplantation in the modern era of new medicine
Shimazu, Y., Mizuno, S., Fuchida, S. I., Suzuki, K., Tsukada, N., Hanagaishi, A., Itagaki, M., Kataoka, K., Kako, S., Sakaida, E., et al
Cancer science. 2021
Abstract
New drugs for multiple myeloma (MM) have dramatically improved patients' overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant-eligible MM patients. To investigate whether the post-ASCT prognosis of MM patients has been improved by new drugs, we conducted a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7,323 patients (4,135 men, 3,188 women, median age 59, range 16-77 years) who underwent upfront ASCT between Jan. 2007 and Dec. 2018. We categorized them by when they underwent ASCT according to the drugs' introduction in Japan: group 1 (2007-2010), group 2 (2011-2016), and group 3 (2017-2018). We compared the groups' post-ASCT OS. The 2-year OS rates (95%CI) of groups 1, 2, and 3 were 85.8% (84.1-87.4%), 89.1% (88.0-90.1%), and 92.3% (90.0-94.2%) (p<0.0001) and the 5-year OS (95%CI) rates were 64.9% (62.4-67.3%), 71.6% (69.7-73.3%), and not applicable, respectively (p<0.0001). A multivariate analysis showed that the post-ASCT OS was superior with these factors: age <65, performance status 0/1, low International Staging System (ISS) stage, receiving SCT =180 days post-diagnosis, better treatment response pre-ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post-ASCT. The post-ASCT OS has thus improved over time (group 1<2<3) with the introduction of new drugs for MM. As the prognosis of high-risk-karyotype patients with ISS stage III remains poor, their treatment requires improvement.
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6.
Title: Impact of Induction Therapy with VRD vs. VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation
Sidana, S., Kumar, S., Fraser, R., Estrada-Merly, N., Giralt, S., Agrawal, V., Anderson, L. D., Jr., Aljurf, M., Banerjee, R., Bashey, A., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Bortezomib-based triplet regimens, specifically bortezomib, lenalidomide and dexamethasone (VRD) and bortezomib, cyclophosphamide and dexamethasone (VCD) are the two most common induction regimens used in transplant-eligible patients with NDMM, with conflicting data on comparative efficacy and outcomes in this population. OBJECTIVES We compared long-term outcomes of multiple myeloma (MM) patients receiving VRD vs. VCD induction prior to autologous stem cell transplant (ASCT). STUDY DESIGN Patients registered with Center for International Blood and Marrow Transplant Registry were included if they underwent ASCT for MM from 01/2013 to 12/2018 within 6 months of diagnosis, received VRD or VCD induction and achieved pre-transplant > partial response. Of 1,135 patients, 914 received VRD and 221 received VCD. RESULTS Patients receiving VCD were more likely to have renal impairment and ISS stage III disease and less likely to receive full dose melphalan (200 mg/m(2)) conditioning (69% vs 80%, p<0.001). Very good partial response rates pre-transplant, post-transplant and at best response in VRD vs. VCD were not significantly different. Maintenance use was more common after VRD (88% vs. 76%, p<0.001) with lenalidomide being the most common agent (80% vs 63%). Patients in the VRD group had higher rates of renal recovery, 74% vs. 43% p<0.001, which may be due to rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed switch over to VRD as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with median progression-free survival (PFS) from transplant of 44.6 vs 34.1 months, p=0.004 and 5-year overall survival (OS) of 79% and 60%, p<0.001, respectively. On multivariate analysis there was no significant survival difference, with hazard ratio (VCD vs. VRD induction) for PFS being 1.22 (95% CI: 0.96-1.55, p=0.10) and OS being 1.33 (95% CI: 0.93-1.92, p=0.12). Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics and pre-transplant response (PFS only). CONCLUSIONS In patients with MM undergoing upfront transplant after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes.
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7.
Outcomes of upfront autologous hematopoietic cell transplantation in patients with multiple myeloma who are 75 years old or older
Munshi, P. N., Vesole, D. H., St Martin, A., Davila, O., Kumar, S., Qazilbash, M., Shah, N., Hari, P. N., D'Souza, A.
Cancer. 2021
Abstract
BACKGROUND Consolidative autologous hematopoietic stem cell transplantation (AHCT) is commonly used for patients with multiple myeloma (MM). We studied AHCT use and outcomes in patients with MM =75 years old. METHODS Patients with MM =75 years old receiving AHCT between 2013 and 2017 in the United States were identified using the Center for International Blood and Marrow Transplant Research database. Relapse and/or progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Covariates used were age, sex, Karnofsky performance score (KPS), HCT-comorbidity index (HCT-CI), International Staging System and/or Durie-Salmon stage, high-risk cytogenetics, melphalan dose, and disease status at and 1 year after transplant. AHCT utilization rate using the Surveillance, Epidemiology, and End Results database was used to estimate specific incidence among =75 years old by race and gender. RESULTS Of 360 patients, 63% were male, 84% were White, 56% had KPS <90, and 57% had HCT-CI =3. The 100-day transplant-related mortality was 1% (0%-2%) with a 2-year REL rate of 27% (95% confidence interval [CI], 22%-33%), PFS of 66% (95% CI, 60%-72%), and OS of 83% (95% CI, 78%-87%). On multivariate analysis, only high-risk cytogenetics was associated with REL risk and decreased PFS. In White males, transplant utilization rate was 5.2%-5.8% compared to 3.5%-4.0% in African American males (P = .02). There was 3.37-3.79% transplant utilization in White females compared to 1.88-2.12% in African American females (P < .01). CONCLUSIONS The use of AHCT was associated with excellent 2-year outcomes in this selected MM population =75 years old. Transplant utilization for patients =75 years old remains low with significant racial and gender disparities.
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8.
Retrospective multi-center study of Adolescent and Young Adult (AYA) Multiple Myeloma in Kansai Myeloma Forum registry
Nakaya, A., Kohara, T., Shibayama, H., Onda, Y., Kanda, J., Kaneko, H., Imada, K., Kida, T., Kosugi, S., Ishikawa, J., et al
International journal of hematology. 2020
Abstract
We retrospectively analyzed the clinical features and outcomes in a real-world cohort of adolescents and the young adult (AYA) patients (age between 16 and 39 years) with symptomatic multiple myeloma (MM) registered with the Kansai Myeloma Forum. 26 patients had been diagnosed as symptomatic MM out of 3284 patients. The prevalence of AYA-MM was 0.8% in this cohort. 81% of the patients was received stem cell transplantation, which may improve outcome. Anemia and hypercalcemia might be prognostic factors, however International Staging System failed to predict overall survival. Five patients developed late-onset adverse events which were serious and life-threatening. The 5-year overall survival was 71.0%. We need to develop the new strategy to overcome AYA-MM.
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9.
Autologous stem cell transplantation in multiple myeloma patients: utilization patterns and hospital effects
Jansen, L., Merz, M., Engelhardt, M., Weisel, K., Scheid, C., Straka, C., Langer, C., Salwender, H., Einsele, H., Kroger, N., et al
Leukemia & lymphoma. 2020;:1-10
Abstract
Evidence on volume outcome associations for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) is limited. We investigated ASCT utilization patterns and volume outcome associations in the German National Registry for Stem Cell Transplants (DRST). MM patients with an upfront ASCT between 1998 and 2014 registered in the DRST were included. ASCT utilization increased strongly from 6% to 17% between 1999 and 2013 with the largest increase for patients aged 60-64 years (8-34%). The mean number of ASCTs conducted in the hospitals per year varied (quintiles, Q1:0.0-8.2 to Q5:31.0-102.7). Center volume was not associated with survival after upfront ASCT (lowest vs. highest center volume, hazard ratios and 95% confidence intervals: 0.95 (0.76-1.18), p = 0.92). Our findings may reflect a high standard of care and degree of specialization of centers performing ASCT for MM in Germany.
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10.
Association between race and treatment patterns and survival outcomes in multiple myeloma: A Connect MM Registry analysis
Ailawadhi, S., Jagannath, S., Lee, H. C., Narang, M., Rifkin, R. M., Terebelo, H. R., Durie, B. G. M., Toomey, K., Hardin, J. W., Gasparetto, C. J., et al
Cancer. 2020;126(19):4332-4340
Abstract
BACKGROUND Studies have reported racial disparities in access to and use of multiple myeloma (MM) treatments between African American (AA) and White patients. Although AA patients demonstrate longer disease-specific survival, this has not uniformly translated into improved survival over time. The association between race and treatment patterns and survival outcomes was analyzed using data from the Connect MM Registry. METHODS The Connect MM Registry is a large US, multicenter, prospective observational cohort study of patients with newly diagnosed MM. Patients who received first-line (1L) stem cell transplantation (SCT) or who did not receive SCT (non-SCT or non-stem cell transplantation [NSCT]) were grouped by race. Effects of race and transplantation status on the use of triplet treatment were estimated using logistic regression. RESULTS Treatment patterns in 1L (types and duration of induction, posttransplantation maintenance) were similar between AA and White patients. SCT rates in 1L (32% vs 36%) and triplet treatment use (AA: 44% for NSCT patients and 72% for SCT patients; and White: 48% for NSCT patients and 72% for SCT patients) during first induction were similar. No significant effect of race or transplantation status on 1L triplet treatment use was observed. Race was not found to be associated with survival outcomes among patients who underwent NSCT; however, AA patients who received SCT had significantly longer overall survival compared with White patients who underwent SCT (not reached vs 88.2 months; hazard ratio, 0.56; 95% CI, 0.35-0.89 [P = .0141]). CONCLUSIONS AA and White patients were found to have similar treatment patterns in the Connect MM Registry, suggesting that both groups had equal access to health care. In this real-world setting, AA patients received standard-of-care treatment, which might have contributed to better MM-specific survival compared with White patients.