Summary
This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) ...patients. Forty‐seven RRMM patients with a median of three prior lines (2–8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1·25 mg/m2 of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1–21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% ≥MR, resulting in a median progression‐free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1‐acid glycoprotein (AAG) at baseline (<800 mg/l) had a superior response (overall response rate of 62% vs. 17%; P = 0·04), which also translated into a longer mPFS (9 vs. 2 months; P = 0·014). In summary, filanesib with pomalidomide and dexamethasone is active in RRMM although with significant haematological toxicity. Most importantly, high levels of AAG can identify patients unlikely to respond to this strategy.
Trial registration: clinicaltrials.gov identifier: NCT02384083.
El mieloma múltiple (MM) es una tumoración hematológica que se caracteriza por la proliferación incontrolada de células plasmáticas y la existencia de una importante cantidad de cadenas libres en ...sangre (CLLs) que puede ocasionar un fallo renal agudo por la precipitación intratubular de ellas, causando nefropatía por cilindros.
La insuficiencia renal aguda es una complicación que puede presentarse en más de un 20% de los pacientes con MM, y la mitad de estos precisarán diálisis.
Presentamos nuestra experiencia de 13 pacientes tratados con diálisis mediante filtros de high cut off (HCO), durante el período comprendido entre julio de 2011 y febrero de 2015.
Se realizan 6 sesiones consecutivas de 6 h de duración, utilizando un filtro de HCO (Theralite® de Gambro®) de 2,1 m2 de superficie. Posteriormente se continúa con sesiones a días alternos de igual duración.
Se realizaron un total de 151 sesiones; una media de 11,6 sesiones/paciente (rango 6-27).
El tratamiento se mostró efectivo para eliminar tanto CLLs kappa como lambda. El porcentaje de disminución de CLLs desde el inicio hasta el final del tratamiento fue del 93,7%. La reducción media por sesión de diálisis fue del 57,7%. En 10 de los 13 casos se recuperó la función renal y los pacientes pudieron permanecer sin diálisis.
No hubo grandes cambios en los niveles de albúmina utilizando un protocolo de infusión de 2 viales de 50mL de albúmina al 20% al final de la sesión de diálisis.
El tratamiento combinado con quimioterapia más diálisis largas con filtros de HCO resultó eficaz para reducir el nivel de CLLs y recuperar un nivel de función renal suficiente en el 77% de los casos. Con filtros de HCO se consigue un ahorro significativo, en contraposición a lo descrito previamente en la literatura.
Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy.
Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis.
We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015.
A total of 6 consecutive 6-hour sessions were performed using a 2.1 m2 HCO filter (Theralite® by Gambro®). Afterwards, further 6-hour sessions were continued on alternate days.
A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6-27).
The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis.
There were no major changes in albumin levels using an infusion protocol of 2 50-mL vials of 20% albumin at the end of the dialysis session.
Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed.
Introduction: Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which ...can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy. Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis. Methods: We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015. A total of 6 consecutive 6-h sessions were performed using a 2.1 m2 HCO filter (Theralite® by Gambro®). Afterwards, further 6-h sessions were continued on alternate days. Results: A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6–27). The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis. There were no major changes in albumin levels using an infusion protocol of 2 50-ml vials of 20% albumin at the end of the dialysis session. Conclusions: Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed.
In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in ...relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
Management of patients with relapsed or refractory (R/R) AL amyloidosis is complex. Some initial reports have shown positive results with daratumumab in heavily pre-treated AL amyloidosis patients. ...In this retrospective multicentric study, 38 patients (mean age 64 ± 9 years) with R/R AL amyloidosis treated with daratumumab were included. Cardiac and renal involvement was present in 76 and 74% of patients, and 42% had ≥3 organs involved. Median number of previous lines of therapy was 2 (range 1-8). Overall hematological response was 72%, including 28% complete responses. The median time to first hematological response was 2 weeks. A high-quality response (≥very good partial response) was obtained in 65% of patients who had never achieved such depth of response previously. Hematological responses were more frequent among patients receiving daratumumab as second-line therapy compared to subsequent therapies (92 vs. 61%). Cardiac and renal organ response rates were 37 and 59%. At 12 months, overall and progression-free survival were 59% (95%CI: 0.36-0.77) and 52% (95%CI: 0.29-0.70), respectively. Daratumumab is a safe and effective drug in the treatment of R/R AL amyloidosis and should be considered early in the course of the disease.
Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could ...help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0-2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.
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