Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study

Abstract Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). The REMIX study is one of the largest prospective, real-world analysis of the effectiveness of IXA-Rd in the setting of RRMM. Conducted in France between August 2017 and October 2019, the REMIX study, a non-interventional prospective study, included 376 patients receiving IXA-Rd in second line or later and followed for at least 24 months. Primary endpoint was the median progression-free survival (mPFS). Median age was 71 years (Q1-Q3 65.0 – 77.5) with 18.4% of participants older than 80 years. IXA-Rd was initiated in L2, L3 and L4 + for 60.4%, 18.1% and 21.5%, respectively. mPFS was 19.1 months (95% CI [15.9, 21.5]) and overall response rate (ORR) was 73.1%. mPFS was 21.5, 21.9 and 5.8 months in patients receiving IXA-Rd as L2, L3, L4 + respectively. Among patients receiving IXA-Rd in L2 and L3, mPFS was similar for patients previously exposed to lenalidomide (19.5 months) than for those lenalidomide naive (not exposed, 22.6 months, p = 0.29). mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older ( p = 0.06) with similar ORR (72.4% and 76.8%) in both subgroups. Adverse events (AEs) were reported in 78.2% of patients including 40.7% of treatment-related AE. IXA discontinuation was due to toxicity in 21% of patients. To conclude, the results of the REMIX study are consistent with the results of Tourmaline-MM1 and confirm the benefit of IXA-Rd combination in real life. It shows the interest of IXA-Rd in an older and frailer population, with an acceptable effectiveness and tolerance

A low lymphocyte-to-monocyte ratio (LMR) predicts PFS, POD24 and OS in previously untreated, high tumor burden follicular lymphoma (FL): an analysis from the RELEVANCE trial

International audienceIntroduction: The peripheral blood LMR has been postulated as an accessible piece of information about the composition of the tumor microenvironment. In a single-center, retrospective, unselected cohort of FL, a low LMR was shown to be associated with an older age and higher tumor burden and to predict for a shorter progression-free and overall survival (PFS, OS) and a higher risk of histological transformation and second primary malignancies (Mozas, Leuk & Lymph, 2020). We explored the impact of the LMR in patients included in the phase III RELEVANCE trial (Morschhauser, NEJM, 2018 and JCO, 2022), which compared rituximab-chemotherapy (R-chemo) with rituximab-lenalidomide (R2) in patients with previously untreated, high tumor burden FL.Methods: Xtile and the maxstat package of R software were used to find the best LMR cutoff based on PFS data and then validated using a truncated power basis spline method. Baseline characteristics, PFS per investigator assessment, early relapse (POD24) and OS were compared between LMR risk groups. Multivariable Cox regression models including the FLIPI score and the treatment arm were built for survival analyses and uni/multivariable logistic regression was used for POD24 analysis.Results: Among the 1030 patients included in the RELEVANCE study, 1018 had LMR data available. The median LMR was 2.5 (range, 0–93) and a LMR cutoff of 2 was found to best predict PFS. Patients with a LMR ≤2 (n = 372, 37%) were older and displayed higher-risk features (Figure A). In the global cohort, a LMR ≤2 was predictive of a shorter PFS (HR = 1.39 Figure B and C) and OS (HR = 1.44), but its negative impact in the multivariable model remained statistically significant solely for PFS (HR for LMR = 1.31). Likewise, a LMR ≤2 was associated with a higher risk of POD24 (univariable OR = 1.84; multivariable OR = 1.71). No significant interaction was observed in the PFS analysis between treatment arms and the LMR, despite the fact that the LMR was significantly associated to PFS only in the R-chemo arm (P = 0.001) and not in the R2 arm (P = 0.08).Conclusions: In this RELEVANCE subanalysis, we demonstrated that the LMR is a strong predictor of PFS and early relapse in high tumor burden FL patients. Whether treatment with immunomodulators such as lenalidomide may abrogate its negative prognostic impact needs to be further investigated

Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia

PURPOSERituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM.METHODSIn this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety.RESULTSTwo hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC (P =.32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P <.01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade a- 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC.CONCLUSIONThis large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM. © American Society of Clinical Oncology

A low lymphocyte-to-monocyte ratio (LMR) predicts PFS, POD24 and OS in previously untreated, high tumor burden follicular lymphoma (FL): an analysis from the RELEVANCE trial

International audienceIntroduction: The peripheral blood LMR has been postulated as an accessible piece of information about the composition of the tumor microenvironment. In a single-center, retrospective, unselected cohort of FL, a low LMR was shown to be associated with an older age and higher tumor burden and to predict for a shorter progression-free and overall survival (PFS, OS) and a higher risk of histological transformation and second primary malignancies (Mozas, Leuk & Lymph, 2020). We explored the impact of the LMR in patients included in the phase III RELEVANCE trial (Morschhauser, NEJM, 2018 and JCO, 2022), which compared rituximab-chemotherapy (R-chemo) with rituximab-lenalidomide (R2) in patients with previously untreated, high tumor burden FL.Methods: Xtile and the maxstat package of R software were used to find the best LMR cutoff based on PFS data and then validated using a truncated power basis spline method. Baseline characteristics, PFS per investigator assessment, early relapse (POD24) and OS were compared between LMR risk groups. Multivariable Cox regression models including the FLIPI score and the treatment arm were built for survival analyses and uni/multivariable logistic regression was used for POD24 analysis.Results: Among the 1030 patients included in the RELEVANCE study, 1018 had LMR data available. The median LMR was 2.5 (range, 0–93) and a LMR cutoff of 2 was found to best predict PFS. Patients with a LMR ≤2 (n = 372, 37%) were older and displayed higher-risk features (Figure A). In the global cohort, a LMR ≤2 was predictive of a shorter PFS (HR = 1.39 Figure B and C) and OS (HR = 1.44), but its negative impact in the multivariable model remained statistically significant solely for PFS (HR for LMR = 1.31). Likewise, a LMR ≤2 was associated with a higher risk of POD24 (univariable OR = 1.84; multivariable OR = 1.71). No significant interaction was observed in the PFS analysis between treatment arms and the LMR, despite the fact that the LMR was significantly associated to PFS only in the R-chemo arm (P = 0.001) and not in the R2 arm (P = 0.08).Conclusions: In this RELEVANCE subanalysis, we demonstrated that the LMR is a strong predictor of PFS and early relapse in high tumor burden FL patients. Whether treatment with immunomodulators such as lenalidomide may abrogate its negative prognostic impact needs to be further investigated

J Clin Oncol

PURPOSE: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. PATIENTS AND METHODS: Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. RESULTS: From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. CONCLUSION: Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML

L’ajout de la lomustine bénéficie aux leucémies myéloïdes aiguës du sujet âgé avec cytogénétique non-défavorable et d’un profil moléculaire à haut risque de l’European Leukemia Net 2017

# 07-03International audienc

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma

Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control. © The Author(s) 2020