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Background: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data., Methods: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020)., Results: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange., Conclusions: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The combination of lenalidomide and dexamethasone (Len-Dex) is an established regimen for patients with relapsed or refractory myeloma. To prolong the benefit of this effective regimen, the Myeloma Program at Princess Margaret Cancer Centre has routinely added a third agent, oral cyclophosphamide (Cy) given weekly, to Len-Dex at disease progression., Patients and Methods: In the present report, we describe the cases of 53 patients who had received Len-Dex-Cy for a minimum of 4 weeks from January 2007 to December 2014 after progression with Len-Dex alone. The dose of added Cy ranged from 250 to 500 mg weekly. The median number of previous regimens, including Len-Dex, was 2 (range, 2-4); 80% of patients had undergone previous autologous stem cell transplantation., Results: The overall rate of response equal to or greater than a partial response was 34%, and clinical benefit (stable disease or better) was observed in 87% of the patients. The median duration of Len-Dex-Cy therapy was 6.9 months (range, 0.9-55.1 months). The median progression-free survival was 6.1 months (range, 4.2-8.1 months) from the addition of Cy and 24.1 months (range, 15.9-32.0 months) from start of Len-Dex., Conclusion: The addition of Cy for patients with myeloma developing progression with Len-Dex was an inexpensive option with manageable toxicity that resulted in a clinically meaningful extension of disease control., (Copyright © 2018. Published by Elsevier Inc.)

High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve excellent clinical responses in patients with POEMS syndrome (Jimenez Zepeda et al., Blood 2010;116:2403; Gertz et al., Am J Hematol 2005;79:319-328; Gherardi et al., Ann Neurol 1994;35:501-505; Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Salem et al., J Immunol 2009;182:2030-2040; Salem et al., Cancer Immunol Immunother 2010;59:341-353; Salem et al., Cell Immunol 2010;261:134-143). However, High-dose melphalan with ASCT should be considered carefully due to its treatment-related morbidity (Vuckovic et al., Blood 2003;101:2314-2317), especially in patients with poor performance status owing to polyneuropathy and multiorgan involvement, such as cardiac, respiratory, and renal failure. Significant increases in the concentration of circulating macrophage colony-stimulating factor, erythropoietin, IL-6, and TNF-α, reach near maximal values at approximately day +12, predating neutrophil engraftment, and clinically manifest with fever, rash and edema (Dispenzieri et al., Eur J Haematol 2008;80:397-406). Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome (ES) (Vuckovic et al., Blood 2003;101:2314-2317). ES occurs in 27-47% of patients who undergo ASCT; mortality rate is reported from 8% to 18% (Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Vuckovic et al., Blood 2003;101:2314-2317). We have therefore reviewed our experience with ASCT in patients with POEMS syndrome who were treated with cyclophosphamide and prednisone as induction therapy followed by cyclophosphamide mobilization with an emphasis on treatment-related morbidity and frequency of ES. Our study confirms that ASCT is a feasible and efficacious treatment for patients with POEMS syndrome. In addition, the use of CP followed by cyclophosphamide mobilization decreases the incidence of PES leading to less morbidity and mortality rates., (2011 Wiley-Liss, Inc.)

Purpose: The combination of oral weekly cyclophosphamide and alternate day prednisone is a convenient regimen for relapsed/refractory multiple myeloma (MM), and we sought to improve its efficacy by adding bortezomib, a proteasome inhibitor with proven antimyeloma activity., Patients and Methods: We conducted a phase I-II trial evaluating six dose levels to define the maximum tolerated dose (MTD) of this combination in relapsed/refractory MM. An additional 10 patients were evaluated at the highest dose level reached., Results: Thirty-seven patients were treated on this study. The MTD was not defined. Both of the highest dose levels of bortezomib tested (1.3 mg/m(2) on days 1, 4, 8, and 11 and 1.5 mg/m(2) on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m(2) per week and prednisone. At these dose levels, the overall response rate was 95% (complete responses [CR] plus partial response plus minimal response), with CR observed in more than 50% of patients. The weekly bortezomib regimen resulted in fewer instances of grade 3 thrombocytopenia and grade 1 to 2 peripheral neuropathy; the 1-year progression-free and overall survival probabilities with this dose level were 83% (95% CI, 73% to 96%) and 100%, respectively., Conclusion: Weekly bortezomib 1.5 mg/m(2) plus oral cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory patients with MM. Further evaluation of this promising regimen is warranted both in relapsed and newly diagnosed disease.

Rituximab is a monoclonal anti-CD20 antibody that is standard of care for treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab (R)-related interstitial pneumonitis (IP) in patients with NHL receiving immunochemotherapy. All patients with NHL who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), R-CHOP or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive R and documented the incidence of IP during and/or post-treatment. In total 560 patients were included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend toward a higher rate in the R group (3.95% vs. 1.3% [odds ratio 3.1, 0.84-17.27, p = 0.074]). Baseline pulmonary computed tomography abnormalities in patients with lymphoma are relatively common. The addition of R to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP. [ABSTRACT FROM AUTHOR]

This single institution, open label Phase I- II dose escalation trial evaluated the safety and efficacy of the combination of lenalidomide (Revlimid®), cyclophosphamide and prednisone ( CPR) in patients with relapsed/refractory multiple myeloma. The maximal administered dose of CPR consisted of cyclophosphamide 300 mg/m2 on day 1, 8, and 15, lenalidomide 25 mg on d 1-21 and prednisone 100 mg every other day in a 28-d cycle. Between November 2007 and June 2009, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full-dose CPR regimen produced no dose-limiting toxicity and was delivered for a median of 16 months (3·5-65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression-free survival was 16·1 months [95% confidence interval ( CI); 10·9-22·5 months], while the median overall survival was 27·6 months (95% CI; 16·8-36·6 months). Only the beta-2 microglobulin level at protocol entry correlated with a better survival ( P = 0·047). These observations compare favourably with other 2- and 3- drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients. [ABSTRACT FROM AUTHOR]

Dexamethasone ± thalidomide with infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide [D(T) PACE] is generally reserved as salvage therapy for aggressive multiple myeloma ( MM) or plasma cell leukaemia ( PCL) resistant to conventional therapies. The efficacy and durability of this potentially toxic regimen in this setting is unclear. We identified 75 patients who received D(T) PACE for relapsed/refractory MM at two tertiary care centres: Princess Margaret Hospital, Toronto and Mayo Clinic Arizona. At time of D(T) PACE, 16 patients had PCL and three patients had leptomeningeal disease. Patients were heavily pretreated (median three prior regimens, range 1-12; prior autologous stem cell transplant [ ASCT] 33%). Overall response rate was 49% (very-good partial response 16%, partial response 33%) with stable disease in an additional 36%. Median progression-free survival ( PFS) was 5·5 months (95% confidence interval [ CI]:4·3-9·8); overall survival ( OS) 14·0 months (95% CI:8·7-19·3). Thirty-five patients proceeded to ASCT or clinical trial, with median PFS for this subset of 13·4 months (95% CI:7·7-20·1) and OS 20·5 months (95% CI:14·8-63·8). D(T) PACE is an effective salvage therapy for heavily pretreated MM patients. Although the overall response rate of 49% in this poor prognosis cohort is reasonable, the PFS is short, suggesting the best role for D(T) PACE is in bridging to definitive therapy, such as transplantation. [ABSTRACT FROM AUTHOR]

The article presents a study on cyclophosphamide, bortezomib and dexamethasone induction therapy for newly diagnosed patients with multiple myeloma (MM). It discusses the development of new therapies for MM, method used to calculate the patients' survival, and the overall response for all patients in the study.