Purpose
The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic ...management of patients treated with an OAD regarding toxicity, medication adherence and quality of life.
Methods
A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018.
Results
Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up OR 0.45 (IC à 95%) (0.23, 0.9)(
P
= 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point.
Conclusions
In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD.
Trial registration
Clinical trial registration is NCT02459483.
Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.
IMPORTANCE: Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove ...nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively. OBJECTIVE: To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability). DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016. INTERVENTIONS: Intensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone. MAIN OUTCOMES AND MEASURES: Primary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death. RESULTS: Among 98 randomized patients, 94 (96%) (median age, 68.8 years interquartile range, 61.2-75.3 years; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% 95% CI, −12.0% to 27.9%, P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% 95% CI, 0.9% to 41.3%, P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% 95% CI, 3.2% to 43.5%, P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died. CONCLUSIONS AND RELEVANCE: Among patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01208818
Therapeutic approaches in Multiple Myeloma (MM) have considerably changed over the last few years, with effective oral chemotherapy and continuous treatment. In this context, the objective of this ...study was to examine the circuitry of an advanced practitioner nurse (APN)-led intervention that provided supportive care for MM patients treated with oral chemotherapy.
This population-based study was conducted at the hematology department - Institut de Cancérologie Lucien Neuwirth (ICLN, Saint-Priest-en-Jarez), from April 2017 to September 2020. A follow-up program was established with a specialized APN in oncology.
All APN interventions were recorded, representing 1240 phone calls and 162 consultations for 42 MM patients. Eighty-two calls were referred to the physician with 45 consultations triggered. Most of the calls were frequent within the few first months, with a high request for information and reassurance, especially for treatment-naive or relapsed patients. In our study, the APN was able to manage multiple side effects through care organization (i.e., hospitalizations, transfusions) and a careful coordination between the primary care team and the hospital.
In order to respond to the high need for care pathway and safety improvement, especially in elderly population, we have initiated an original follow-up by an APN for MM patients treated with oral chemotherapy. While the role of APN has become prominent in the oncology field in recent years, its holistic approach has to be emphasized in further studies to bring a comprehensive perspective to health care coordination in the future.
Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often proposed for patients with comorbidities. To enhance engraftment and limit graft-versus-host ...disease (GVHD), antithymoglobulin (ATG) is usually used. However, the dose needed remains unclear unlike myeloablative conditioning. In order to clarify this point, we conducted a retrospective study on patients who received a reduced intensity conditioning allo-HSCT based on a 2-day fludarabine and busulfan treatment with either 1 or 2 days of ATG treatment. One hundred and eight patients received 2.5 mg/kg (ATG2.5) and another 60 patients 5 mg/kg (ATG5). The median follow-up was 36 months. The median overall survival was 39 months and the median disease-free survival 45 months. In multivariate analysis, overall nonrelapse mortality (NRM) was independently influenced by the acute GVHD grade III-IV (p < 0.001) and ATG dose (30 vs. 21% for ATG5; p = 0.008). Despite heterogeneity of populations, using proportional-hazard assumptions, we have been able to observe in multivariate analysis a lower NRM in the ATG5 group. This leads to a statistically higher overall survival for the ATG5 group. In conclusion, 2 days of ATG decrease NRM independently without increasing the risk of relapse or infectious disease.
High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously ...reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously IV) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.
•The Bor-HDM (200 mg/m2) conditioning regimen is not superior to HDM alone in de novo multiple myeloma.•HDM (200 mg/m2) remains the standard-of-care conditioning for transplantation in multiple myeloma.
Display omitted
We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and ...acute kidney injury (AKI) without need for dialysis.
After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group).
Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41
47 responders in the BD and C-BD groups, respectively; relative risk RR, 0.87;
= .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76;
= .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group
10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died.
This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.
▪
Multiple myeloma (MM) is often revealed by acute kidney injury (AKI) usually related to MCN. Recovery of renal function is a key prognostic factor. With novel anti-myeloma agents, HD-independence ...occurs in about 30% of pts with severe AKI, advocating for the use of additional strategies to rapidly remove circulating monoclonal free light chains (FLC).
We designed a prospective randomized trial to compare the HD-independence rate in pts with inaugural severe AKI secondary to biopsy-proven MCN, treated by intensive HD (8 sessions over the first 10 days, then thrice a week) using either a HCO dialyzer or a conventional high-flux dialyzer. In both groups, pts received 21-day courses of Bortezomib and dexamethasone (BD), reinforced by cyclophosphamide after 3 cycles in the absence of haematological response (HR).
Between 2011 and 2015, 98 pts were randomised. One pt withdrew consent, and 3 had main exclusion criteria. Baseline characteristics in the control arm (n=48) and HCO arm (n=46) were close, including similarly high serum FLC levels (median 6,015mg/L).
HD independence was achieved in 33% and 43% (p= 0.31) at 3 and in 37.5% and 60 % (p=0.03) at 6 mo, in the control and HCO arms, respectively. HR rate of very good partial response or above at 3 mo based on FLC was 48% in control and 59% in HCO groups (p=0.29). Tolerance of HD schedule and of chemotherapy was acceptable in both arms. At 12 mo, 17 pts have died (10 vs 7).
This randomized trial demonstrates that in MM patients with MCN and severe AKI treated with a bortezomib-based regimen, intensive HCO-HD results in higher renal recovery rate than HD with conventional high-flux dialyzers.
Augeul-Meunier:janssen: Consultancy; gilead: Consultancy. Benboubker:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.
•Active HHV-6 infection occurred in 11.2% of autologous stem cell recipients.•HHV-6 infection is associated with delayed neutrophils and platelets recoveries.•HHV-6 infection is associated to ...increased frequency of non-infectious complications.•Non-infectious complications are more severe when associated to HHV-6 infection.
to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients.
HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads.
from July 2012 to February 2015, 196 adult patients undergoing ASCT were enrolled. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19% at 40 days after transplantation. The onset of active HHV-6 infection occurred with a median of 13 days after stem cell re-infusion. HHV-6 infection was associated with an increased frequency of non-infectious complications (OR = 5.05; 95%CI 1.78–14.32; P < 0.001). Moreover, the severity of these non-infectious complications was higher in recipients exhibiting HHV-6 infection (OR = 4.62; 95%CI 1.32–16.2; p < 0.01). Delayed neutrophils 10 (IQR: 8–14) vs 8 (IQR: 6–11) days and platelets recoveries 15 (IQR: 11.8–18.5) vs 8 (IQR: 4–14) days were observed in patients with active HHV-6 infection compared to non-infected ones.
in this study, 11.2% ASCT recipients presented active HHV-6 infection associated with significantly delayed hematologic reconstitution.
Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is ...associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m
) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m
melphalan is a beneficial procedure for MM patients with renal failure.
Since the first descriptions by Slavin et al, indications of allogeneic haematopoietic stem cell transplantations (AHSCT) with fludarabine and busulfan conditioning regimen (CR) have increased. The ...use of strongly immunosuppressant products such as antithymocyte globulin (ATG) increase transplant engraftment and limit the risk of GVHD but with a higher risk of infectious complications. Recently, with myeloablative conditioning regimen (MAC), one randomized and one retrospective studies showed a reduction of cGVHD incidence (1,2). In reduced CR (RIC), the results are contradictory. In large series, the use of ATG seems to increase the relapse rate and ultimately influence the overall survival (OS) (3). Therefore, the ATG dose in RIC conditioning remains discussed. In order to clarify this point, we conducted a retrospective study on patients who received a fludarabine-busulfan RIC AHSCT with easer one or tow days of ATG.
168 consecutive patients, followed between January 2000 and December 2011 in 2 French centers were analysed. RIC was based on Fludarabine 150 mg/m² and Busulfan for 2 consecutive days. Selected dose of ATG (Thymoglobuline®) administered were easer 2.5 or 5 mg/kg/day. Information concerning donors, recipients, conditioning regimen, graft harvesting and follow-up were collected using prospectively designed forms from Promise database.
108 patients had received 2.5 mg/kg (ATG1) versus 60 patients 5 mg/kg (ATG2). Median follow-up was of 60 months range 18-148. Median age was 58 years with 99 males and 69 females. Diagnosis included AML/MDS (n=84), ALL (n=7), CML (n=7), lymphoma or CLL (n=52), and myeloma (n=18). Donors were matched sibling (n=74) or unrelated (n= 94). Only 6.5% of transplants were in HLA mismatch. Median time to recovery of polynuclear neutrophils was 17 days (range 3-73.2). Time to platelet reconstitution was 11 days (range 3-39). Median of OS was 39 months. In multivariate analysis, disease status at transplant, aGVHD severity (III-IV) (p=.000044; 3.52 (1.92-6.45) and cGVHD occurrence were the prognostic parameters statically significant. Median of Disease Free Survival (DFS) was 45 months (1-111) with no difference between ATG1 and ATG2 or other parameters. Death attributed to disease progression seemed to be higher in ATG1 group but difference failed to reach statistical significance (25% versus 17%, p=0.21).
Incidence of non-relapse mortality (NRM) at 3 months was 5% and the global NRM at 26%. In multivariate analysis, two parameters influence significantly the NRM, the aGVHD incidence (III-IV) (p=.00016; 8.03(2.73-23.65)) and the dose of ATG delivered (31% vs. 16% for ATG2; p=.048; 2.36 (1.01-5.54)). Interesting, NRM was principally significant in late events (> 3 months) with more death by GVHD or infectious disease in ATG1 group.
No difference between ATG1 and ATG2 group was noted for hematopoietic reconstitution, rejection rate (2 in each group of SAL) and incidence of aGvHD. Although cumulative incidence of cGvHD seemed to be higher in ATG1 group, difference failed to reach statistical significance (42% versus 33%, p=0.23).
Our result show that 2 days of ATG decrease NRM independently of disease, source of donor, graft or GVHD incidence without increasing the risk of relapse or infectious disease. These results are compatible with previous results observed with MAC. According to our results, in RIC, higher dose of ATG might be recommended.
1. Socie G, et al; Blood. 2011 Jun 9;117(23):6375–82.
2. Mohty M, et al; Leukemia. 2010 Sep 30;24(11):1867–74.
3. Soiffer RJ, et al. Blood. 2011 Jun 23;117(25):6963–70.
No relevant conflicts of interest to declare.
PDF
