scholarly journals The Role of Monoclonal Antibodies in the First-Line Treatment of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma

2020 ◽  
Vol 14 (1) ◽  
pp. 20
Author(s):  
Francesca Bonello ◽  
Mariella Grasso ◽  
Mattia D’Agostino ◽  
Ivana Celeghini ◽  
Alessia Castellino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Elderly Patients ◽  
Residual Disease ◽  
Real Life ◽  
Newly Diagnosed ◽  
First Line ◽  
Large Variability ◽  
Wide Range

Elderly transplant-ineligible (NTE) patients represent the majority of patients affected by multiple myeloma (MM). Elderly patients are a highly heterogeneous population, with large variability in health and functional status. Thus, choosing their optimal treatment is challenging. A wide range of first-line treatments is available, and novel-agent combinations, including monoclonal antibodies (mAbs), have recently entered clinical practice. The combination of the anti-CD38 mAb daratumumab with bortezomib, melphalan and prednisone (Dara-VMP) or lenalidomide and dexamethasone (Dara-Rd) demonstrated impressive advantages in terms of progression-free survival and minimal residual disease negativity, as compared to VMP and Rd, without safety concerns. Another anti-CD38 mAb, isatuximab, is showing encouraging results, and new isatuximab-based combinations might enter clinical practice in the future. Nevertheless, available data come from clinical trials with selected patient populations and, to date, the manageability of these regimens in real-life patients or in frail patients remains unknown. Frailty-tailored treatments, including mAbs, are under evaluation in preliminary studies. In this review, we analyze recently approved mAb-based treatments for NTE newly diagnosed MM patients and new combinations under evaluation, focusing on the efficacy and safety of these regimens and on open issues regarding the choice of therapy for elderly patients.

scholarly journals Real-Life Experience With First-Line Therapy Bortezomib Plus Melphalan and Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma Ineligible for High Dose Chemotherapy With Autologous Stem-Cell Transplantation

2021 ◽  
Vol 8 ◽  
Author(s):  
Gabriele Buda ◽  
Maria Livia Del Giudice ◽  
Elisabetta Antonioli ◽  
Francesco Ghio ◽  
Enrico Orciuolo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Elderly Patients ◽  
Autologous Stem Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Introduction: Currently, the regimen with bortezomib plus melphalan and prednisone (VMP) is a standard treatment for multiple myeloma and it is recommended as the first-line therapy for patients with multiple myeloma (MM) ineligible for high-dose chemotherapy with autologous stem-cell transplantation.Objectives: Participants of the clinical trial are highly selected populations; therefore, the aim of this study was to present observations from real practice that can provide important information for practitioners and to investigate clinical outcomes of VMP regimen in elderly patients with newly diagnosed MM.Patients and Methods: We retrospectively analyzed the data on the efficacy and survival parameters, such as overall survival (OS) and event-free survival (EFS), with attention to the effect of gender, age and International Staging System (ISS) stage, of VMP regimen in 164 patients with newly diagnosed MM not eligible for high-dose chemotherapy with autologous stem-cell transplantation (median age, 75 years; range, 60–86 years).Results: Patients aged 75 years or older constituted 50.6% of the study cohort. Frail patients were 10.36%, according to the clinical frailty scale of geriatric assessment (GA). A total of 1203 courses of VMP regimen (mainly VMP 1–29, 99.16 %) were administered. The median cumulative delivered dose of bortezomib was 46.8 mg/m2. The overall response rate (ORR), including all patients with a partial response or better, was 81.7% and the complete response rate (CRR) was 10.36 %. After a median 38.51 months of follow-up, the median overall survival (OS) was 34.33 months; the median event-free survival (EFS) after VMP and second-line therapy (mainly Rd, 56.31%) were 18.51 and 10.75 months, respectively. In the subgroup of patients with 75 years or older the median OS was 29.76 months; the median EFS after first and second-line therapy were 17.76 and 8.93 months, respectively. The hazard ratio for OS was 2.276 (p-value 0.046) and for EFS was 1.507 (p-value 0.055) for the ISS stage II and III group. Age and gender were not negative predictors of survival.Conclusions: VMP treatment is highly effective in the first-line therapy of elderly patients with multiple myeloma ineligible for HDT with auto-SCT.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

scholarly journals Treatment patterns and outcomes in elderly patients with newly diagnosed multiple myeloma: results from the Connect® MM Registry

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Hans C. Lee ◽  
Sikander Ailawadhi ◽  
Cristina J. Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Treatment Patterns ◽  
Newly Diagnosed

Incorporation of plasma-based next-generation sequencing to improve guideline-concordant molecular testing in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 14-14
Author(s):  
Charu Aggarwal ◽  
Melina Elpi Marmarelis ◽  
Wei-Ting Hwang ◽  
Dylan G. Scholes ◽  
Aditi Puri Singh ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Practice Change ◽  
Molecular Testing ◽  
Tier 2 ◽  
Newly Diagnosed ◽  
Next Generation ◽  
First Line ◽  
Tier 1 ◽  
Tier 3 ◽  
The Impact

14 Background: Current NCCN guidelines recommend comprehensive molecular profiling for all newly diagnosed patients with metastatic non-squamous NSCLC to enable the delivery of personalized medicine. We have previously demonstrated that incorporation of plasma based next-generation gene sequencing (NGS) improves detection of clinically actionable mutations in patients with advanced NSCLC (Aggarwal et al, JAMA Oncology, 2018). To increase rates of comprehensive molecular testing at our institution, we adapted our clinical practice to include concurrent use of plasma (P) and tissue (T) based NGS upon initial diagnosis. P NGS testing was performed using a commercial 74 gene assay. We analyzed the impact of this practice change on guideline concordant molecular testing at our institution. Methods: A retrospective cohort study of patients with newly diagnosed metastatic non-squamous NSCLC following the implementation of this practice change in 12/2018 was performed. Tiers of NCCN guideline concordant testing were defined, Tier 1: complete EGFR, ALK, BRAF, ROS1, MET, RET, NTRK testing, Tier 2: included above, but with incomplete NTRK testing, Tier 3: > 2 genes tested, Tier 4: single gene testing, Tier 5: no testing. Proportion of patients with comprehensive molecular testing by modality (T NGS vs. T+P NGS) were compared using one-sided Fisher’s exact test. Results: Between 01/2019, and 12/2019, 170 patients with newly diagnosed metastatic non-Sq NSCLC were treated at our institution. Overall, 98.2% (167/170) patients underwent molecular testing, Tier 1: n = 100 (59%), Tier 2: n = 39 (23%), Tier 3/4: n = 28 (16.5%), Tier 5: n = 3 (2%). Amongst these patients, 43.1% (72/167) were tested with T NGS alone, 8% (15/167) with P NGS alone, and 47.9% (80/167) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS: 95.7% (79/80) compared to T alone: 62.5% (45/72), p < 0.0005. Prior to the initiation of first line treatment, 72.4% (123/170) patients underwent molecular testing, Tier 1: n = 73 (59%), Tier 2: n = 27 (22%) and Tier 3/4: n = 23 (18%). Amongst these, 39% (48/123) were tested with T NGS alone, 7% (9/123) with P NGS alone and 53.6% (66/123) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS, 100% (66/66) compared to 52% (25/48) with T NGS alone (p < 0.0005). Conclusions: Incorporation of concurrent T+P NGS testing in treatment naïve metastatic non-Sq NSCLC significantly increased the proportion of patients undergoing guideline concordant molecular testing, including prior to initiation of first-line therapy at our institution. Concurrent T+P NGS should be adopted into institutional pathways and routine clinical practice.

Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8010-8010
Author(s):  
Noemi Puig ◽  
Bruno Paiva ◽  
Teresa Contreras ◽  
M. Teresa Cedena ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Residual Disease ◽  
Newly Diagnosed ◽  
Time Points ◽  
Minimal Residual

8010 Background: Analysis of minimal residual disease (MRD) in the bone marrow (BM) of patients with multiple myeloma (MM) is accepted by the IMWG to evaluate treatment efficacy and is a well-established prognostic factor. However, there is an unmet need to explore the clinical value of MRD in peripheral blood (PB). Methods: Newly diagnosed MM patients enrolled in the GEM2012MENOS65 trial received six induction (Ind) cycles of bortezomib, lenalidomide, and dexamethasone (VRD) followed by autologous stem cell transplantation (ASCT) and 2 further cycles of consolidation (Cons) with VRD. MRD was analyzed in BM using Next Generation Flow (NGF) and in serum by Mass Spectrometry (MS) using IgG/A/M, κ, λ, free κ and free λ specific beads, both after Ind, at day 100 after ASCT, and after Cons. Sequential samples from the first 184 patients were analyzed. Results: Results of both methods were in agreement (NGF+/MS+ and NGF-/MS-) in 83% of cases post-Ind (152/184), 80% post-ASCT (139/174) and 76% post-Cons (128/169). Stratifying by the log range of MRD by NGF, discordances (NGF+/MS- and NGF-/MS+) seemed to increase at the lower MRD ranges, being 22%, 21% and 19% from ≥10−5 to <10−4 and 21%, 21%, 23% at ≥x10−6(post-Ind, ASCT and Cons, respectively). Analysis of discordances showed that they could be partly explained by the higher percentages of cases found to be positive by MS as compared by NGF at part of the time-points analyzed and at each log range of MRD. From ≥10−5 to <10−4, MRD was detected by NGF in 36%, 28%, 20% of cases post-Ind, ASCT and Cons, respectively vs MS in 37%, 29%, 21% of them; at ≥x10−6, NGF was positive in 11%, 14%, 19% of cases vs MS in 23%, 19% and 16% of them. Considering NGF as a reference, the negative predictive value (NPV) of MS per MRD range (≥10−5 to <10−4 and ≥x10−6, respectively) was: post-Ind: 83% (p<0,0001), 94% (p=0,034); post-ASCT 86% (p<0,0001), 90% (p=0,022); post-Cons 89% (p<0,0001), 85% (p=0,0469). Despite these discordances, the prognostic value of each technique in terms of undetectable MRD and progression-free survival (PFS) was consistent at all time-points (Table) and further, discordant cases (NGF+/MS- and NGF-/MS+) did not display a significantly different PFS as compared to NGF-/MS- cases. Conclusions: The results of MRD assessed by NGF in BM and by MS in PB show a significant concordance and are associated with a similar prognostic value analyzed in terms of PFS. Given its high NPV, MRD in peripheral blood by MS provides a gateway for BM aspiration/biopsy and MRD assessment by NGF.[Table: see text]

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