We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 10 /l and peripheral blood plasma cell count ≥20 × 10 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.
The role of c-myc in multiple myeloma (MM) is controversial. We conducted a retrospective study of 117 patients with MM diagnosed between 2004 and 2010 at Herlev Hospital. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) made from diagnostic bone marrow aspirates. Clinical data were obtained from the Danish Multiple Myeloma Database (DMMD). Overexpression of c-myc was found in 40% of patients. MYC translocation was found in 10% of patients. Overexpression of c-myc was not associated with MYC translocation. Overexpression of c-myc was associated with hypercalcemia (p = 0.02) and extramedullary myeloma (p < 0.01). Overexpression of c-myc was associated with shorter overall survival (OS) by multivariable analysis of the entire patient cohort [HR 1.92 (1.06-3.45), p = 0.03] and univariable analysis of high-dose-therapy (HDT)-ineligible patients [HR 2.01 (1.05-3.86), p = 0.04]. Further studies of c-myc overexpression in larger cohorts of patients with MM are warranted.
This multicenter retrospective study included 101 patients (median age 62 years) with secondary plasma cell leukemia (sPCL). The median time from initial multiple myeloma diagnosis to sPCL was 31 months. Fifty-five out of 72 patients (75%) who received any therapy were treated with immunomodulators (IMiDs) and/or proteasome inhibitors (PIs), and 14/72 (19%) underwent salvage autologous stem cell transplantation (ASCT). The overall response rate in patients who received ASCT or PI (either alone or in combination) was higher than in those who did not (93% vs. 36% and 60% vs. 30%, respectively). The median overall survival (OS) in patients who received therapy was 4.2 months (95% CI: 1.3; 8.0) with a 1-year OS of 19%. Platelet count ≤100 × 10/L at sPCL diagnosis was the only independent predictor of a poorer OS in treated patients (HR = 3.98, p = .0001). These findings suggest that patients with sPCL may benefit from salvage ASCT- and PI-based regimens.
In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.
Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.
In this retrospective study we reviewed the clinical course of every patient with multiple myeloma treated from 2006 to 2016 at Vejle Hospital: 303 patients with a median age of 69 years at diagnosis received a median of four (range 1-18) lines of therapy; 149 in a 2006-2010 cohort and 154 in a 2011-2016 cohort. After initiation of treatment, the median decrease in the number of patients per each subsequent line of therapy was 22%. Lenalidomide-dexamethasone (n = 156), bortezomib-dexamethasone (n = 107), and bortezomib-lenalidomide-dexamethasone (n = 84) were the most commonly used regimens. The partial response or better rate was 78%, 58%, 55%, and 44% in lines of therapy one to four, respectively. The median (95% confidence interval [CI]) progression-free survival was 18 (15-22), 10 (8-13), 8 (7-10), and 6 (4-8) months in lines of therapy one to four, respectively. The median (95% CI) overall survival (OS) was 4.1 (3.7-4.8) years. Compared with the 2006-2010 cohort, patients in the 2011-2016 cohort had longer OS; 5.3 (4.7 to not reached) versus 3.4 (2.7-4.0) years, p < 0.0001. This was especially true in patients not treated with high-dose therapy and autologous stem cell transplantation; 4.7 (3.2-5.9) versus 2.6 (2.0-3.3) years, p = 0.0052. Patients in the 2011-2016 cohort were on treatment during a greater part of their life and had higher exposure to high-dose melphalan with autologous stem cell transplantation, lenalidomide, pomalidomide, daratumumab, and carfilzomib.
Presentation with severe acute kidney injury due to cast nephropathy (CN) is a medical emergency in multiple myeloma (MM), with high risk of dialysis-dependent renal failure and death. Accrual of patients with CN into interventional studies is difficult, while phase III trials exclude patients with severe renal insufficiency. Real-world data are warranted. We assessed 2252 patients from the population-based Danish Multiple Myeloma Registry (DMMR) who were diagnosed between 2013 and 2017. We identified 204 patients with clinically-suspected CN, defined as serum creatinine concentration >177 μmol/L and serum free light chain (sFLC) concentration >1000 mg/L at the time of diagnosis. The median age was 72 years. Thirty-one percent of patients presented with dialysis-dependent renal failure. Kidney biopsies were performed in 19% of patients and showed CN in 74% of cases. Despite prompt initiation of bortezomib-based therapy in 94% of patients, 33% of patients died in the first year after diagnosis. Compared with the rest of the patients in the DMMR with symptomatic MM, patients with clinicallysuspected CN had worse overall survival (OS) irrespective of transplant eligibility. Achievement of renal recovery was associated with deep reductions of involved sFLC. Achievement of very good partial response or better in the first line of therapy and/or deep reduction of involved sFLC at 3 months after initiation of therapy were associated with superior OS. In conclusion, MM patients presenting with clinically-suspected CN have an alarmingly high one-year mortality when treated with current standards of care. Early and deep hematologic response is crucial for survival. 1 | INTRODUCTION Renal failure, defined by serum creatinine higher than 177 μmol/L, occurs in approximately 20%-30% of patients with multiple myeloma (MM) at the time of diagnosis. 1-4 Severe renal impairment requiring hemodialysis occurs in 3%-9% of all patients with newly-diagnosed MM, and unless renal function is recovered, it leads to considerable mortality during the first months after diagnosis. 1,2,5-10 Myeloma cast nephropathy (CN) is the most common form of monoclonal immunoglobulin-mediated kidney disease. 11,12 It results from the interaction of excessive amounts of monoclonal light chains with
Objective We describe real‐world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). Method First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005–2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. Results We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high‐risk MM in a real‐ world‐population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. Conclusion National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.