Minimal residual disease clinical monitoring and depth of response in multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8026-8026
Author(s):  
Joaquin Martinez-Lopez ◽  
Sandy Wai Kuan Wong ◽  
Nina Shah ◽  
Natasha Bahri ◽  
Kaili Zhou ◽  
...  
Keyword(s):  
Decision Making ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Clinical Decision Making ◽  
Newly Diagnosed ◽  
Disease Evolution ◽  
Time Points ◽  
Depth Of Response ◽  
Relapsed Disease ◽  
The Impact

8026 Background: MRD assessment is a known surrogate marker for survival in multiple myeloma (MM). Most data come from patients enrolled in clinical trials. We present a single institution’s experience assessing MRD in patients receiving frontline therapy and therapy for relapsed disease. We describe the impact of depth, duration, and direction of response on prognosis. Methods: 181 MM patients at University of California, San Francisco (UCSF) from 2008 to 2016. 126 were newly diagnosed and 55 in ≥ 2nd line. MRD was assessed in patients achieving VGPR or better by IMWG criteria. MRD assessment was performed by NGS (Adaptive Biotechnologies, Seattle, WA). PFS curves were plotted by the Kaplan-Meier method, and the log-rank test was used to estimate statistical significance. Results: 398 MRD samples were analyzed. MRD was available at 3 time points for 59 patients and 2 time points for 36 patients. Median follow up was 26m. Overall, 66 of 181 patients (36%)achieved MRD- ( < 10-6) on one or more samples. In the newly diagnosed group, 43 of 126 (34%), achieved MRD- at least once. These patients had a prolonged PFS versus patients who were persistently MRD+ (NR vs 49m, p = 0.006). Of the 55 patients who received therapy for relapsed disease, 21 achieved MRD- (38%) and PFS was also prolonged versus patients who remained MRD+ (53m vs 23m, p = 0.03). We analyzed the effects of depth of response. Patients who were MRD- or who were MRD+, at a very low level (between 10-5and 10-6), had a better prognosis than those with higher disease burdens ( > 10-5) (p = 0.001). Finally, we analyzed the effect of repeated MRD monitoring on PFS. Three categories were identified in newly diagnosed patients: (A) patients with ≥3 MRD- samples, (B) patients with continuously declining detectable clones, and (C) patients with a stable number of clones. Groups A and B had a more prolonged PFS than group C (NR vs 31m, p < 0.0001). Conclusions: MRD assessment in a real-world setting has the same predictive power as that seen in clinical trials. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. This study lends support to the concept of MRD-driven decision-making and helps validate the relevance of MRD.

Impact of Response Quality on Survival Outcomes in Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): Results from the First Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3458-3458 ◽  
Author(s):  
Nizar J Bahlis ◽  
Alessandro Corso ◽  
Lars-Olof Mugge ◽  
Zhi-Xiang Shen ◽  
Pierre Desjardins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Failure Time ◽  
P Value ◽  
Newly Diagnosed ◽  
Response Quality ◽  
Depth Of Response ◽  
Duration Of Response ◽  
Intent To Treat ◽  
The Impact

Abstract Background: In the pivotal phase 3 FIRST trial, continuous lenalidomide plus low-dose dexamethasone (Rd) improved progression-free survival (PFS), overall survival (OS), and response compared with fixed-duration treatment (Tx) with either Rd or the combination of melphalan-prednisone-thalidomide (MPT) in transplant-ineligible NDMM pts (Facon, Blood 2013). Here we examine if pts achieving complete remission (CR) or at least very good partial response (≥ VGPR) equally benefit from continuous Rd. Methods: Pts were randomized to continuous Rd until progressive disease (PD; N= 535); Rd for 18 cycles (72 weeks) (Rd18; N = 541); or MPT for 12 cycles (72 weeks) (N = 547). The primary endpoint was PFS (continuous Rd vs. MPT). The secondary endpoints included OS, response rate (assessed using IMWG criteria), time to response, duration of response (DOR), time to Tx failure, time to next antimyeloma Tx, health-related quality of life, and safety. With a data cutoff of May 24, 2013, the median follow-up was 37.0 months (mos). Results: In pts who achieved ≥ VGPR, median PFS was significantly longer (NR) with continuous Rd compared with Rd18 (31.0 mos; HR = 0.46; P < 0.01) or MPT (34.7 mos; HR = 0.55; P < 001). Even greater benefit of continuous Rd was observed compared with Rd18 or MPT in pts who achieved CR, where the median PFS with continuous Rd was NR vs. 45.2 mos with Rd18 (HR = 0.29; P < 0.01) and 44.6 mos with MPT (HR = 0.28; P < 0.01) (Table 1). In the intent-to-treat population, duration of response (DOR) was 35 mos with continuous Rd, which was significantly longer of almost a year vs. Rd18 (22.1 mos; HR = 0.60; P < 0.01) or MPT (22.3; HR = 0.63; P < 0.01). Importantly, the DOR was significantly longer with continuous Rd vs. Rd18 or MPT across all response categories, including pts with CR. Median duration of CR was NR vs. 43.6 mos in pts receiving continuous Rd vs. Rd18 (HR = 0.29; P < 0.01); ≥ VGPR, NR vs. 29.9 mos (HR = 0.46; P < 0.01); and ≥ PR, 35 mos vs. 22.1 mos (HR = 0.60; P < 0.01). In pts who achieved CR, 88% were disease-free after 36 mos with continuous Rd vs. 55% Rd18 and 54% MPT. In terms of OS, only interim data on continuous Rd vs. Rd18 or MPT on depth of response in the subgroups is presented in table 1. Conclusions: The DOR was significantly longer (12-18 mos) as was PFS in pts treated with continuous Rd vs. Rd18 or MPT regardless of the depth of response. The benefits of continuous Rd were more pronounced in pts who achieved a greater depth of response (≥ VGPR). These data suggest that continuing Tx after best response may further help in controlling the disease and delaying PD, especially in pts achieving CR. Longer follow-up may be needed to determine the impact of response quality on OS in pts receiving continuous Tx. Abstract 3458. Table 1. PFS, DOR, and OS in pts with NDMM CR (n = 209) ≥ VGPR (n = 618) ≥ PR (n = 1140) ≤ SD (n = 483) ITT pts (N = 1623) Median PFS (mos) Rd NR NR 37.7 3.7 27.4 Rd18 45.2 31.0 24.0 4.6 21.3 MPT 44.6 34.7 26.3 4.9 21.8 PFS, HR (95% CI); P-value Rd vs. MPT 0.28 (0.13–0.61); P < 0.01 0.55 (0.40–0.76); P < 0.01 0.67 (0.55–0.82); P < 0.01 1.60 (1.22–2.11); P < 0.01 0.68 (0.56–0.83); P < 0.01 Rd vs. Rd18 0.29 (0.15–0.58); P < 0.01 0.46 (0.34–0.60); P < 0.01 0.60 (0.49–0.72); P < 0.01 1.10 (0.82–1.48); P = 0.53 0.68 (0.55–0.83); P < 0.01 Median DOR (mos) Rd NR NR 35.0 – 35.0 Rd18 43.6 29.9 22.1 – 22.1 MPT 41.9 31.8 22.3 – 22.3 DOR, HR (95% CI); P-value Rd vs. MPT 0.27 (0.13–0.59); P < 0.01 0.54 (0.39–0.74); P < 0.01 0.63 (0.51–0.76); P < 0.01 – 0.63 (0.51–0.76); P < 0.01 Rd vs. Rd18 0.29 (0.15–0.59); P < 0.01 0.46 (0.35–0.61); P < 0.01 0.60 (0.50–0.72); P < 0.01 – 0.60 (0.50–0.72); P < 0.01 Median OS (mos) Rd NR NR 55.1 33.2 55.1 Rd18 NR NR NR 26.8 53.6 MPT NR NR NR 31.6 48.2 OS, HR (95% CI); P-value Rd vs. MPT 0.59 (0.23–1.49); P = 0.26 0.77 (0.50–1.180; P = 0.23 0.85 (0.64–1.11); P = 0.23 0.98 (0.72–1.33); P = 0.89 0.78 (0.64–0.96); P < 0.02 Rd vs. Rd18 0.84 (0.34–2.07); P = 0.71 0.82 (0.56–1.22); P = 0.33 0.90 (0.69–1.17); P = 0.45 0.97 (0.70–1.35); P = 0.85 0.90 (0.73–1.10); P =0.31 CI, confidence interval; ITT, intent-to-treat. Disclosures Bahlis: Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Stoppa:Celgene, Janssen: Honoraria. Decaux:Celgene and Janssen-Cilag : Consultancy, Honoraria. Marit:Celgene, Janssen: Congress expenses Other. Demuynck:Janssen-Cilag: Honoraria. Ervin-Haynes:Celgene: Employment. Leupin:Celgene: Employment. Marek:Celgene: Employment, Equity Ownership. Chen:Celgene: Employment. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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]

AAC Assessment and Clinical-Decision Making: The Impact of Experience

2012 ◽  
Vol 28 (3) ◽  
pp. 148-159 ◽  
Author(s):  
Aimee Dietz ◽  
Wendy Quach ◽  
Shelley K. Lund ◽  
Miechelle McKelvey
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The Impact

Standardized Synoptic Cancer Pathology Reports — So What and Who Cares?: A Population-Based Satisfaction Survey of 970 Pathologists, Surgeons, and Oncologists

2013 ◽  
Vol 137 (11) ◽  
pp. 1599-1602 ◽  
Author(s):  
Sara Lankshear ◽  
John Srigley ◽  
Thomas McGowan ◽  
Marta Yurcan ◽  
Carol Sawka
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Physician Satisfaction ◽  
Cross Sectional ◽  
Cancer Pathology ◽  
Report Turnaround Time ◽  
Significant Difference ◽  
Pathology Reporting ◽  
The Impact

Context.—Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. Objective.—To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. Design.—A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. Results.—A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P &lt; .001) and ease of finding information for clinical decision making (r = 0.663, P &lt; .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. Conclusion.—This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

scholarly journals Comprehensive Geriatric Assessment in Consecutive Newly-Diagnosed Elderly Multiple Myeloma Patients in China: A Multicentered, Prospective, Non-Interventional Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5493-5493
Author(s):  
Yuan Yao ◽  
Dehui Zou ◽  
Aijun Liao ◽  
Xiaoxia Chu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Geriatric Assessment ◽  
Real World ◽  
Comprehensive Geriatric Assessment ◽  
Newly Diagnosed ◽  
Frail Patients

Background: Multiple Myeloma (MM) is a disease of the elderly, whose prognoses are highly heterogeneous. Hence International Myeloma Working Group (IMWG) proposed geriatric assessment (GA) in 2015, including daily activity and comorbidity status, to better discriminate between fit and frail patients (Palumbo et al, 2015). However, IMWG recruited patients from clinical trials instead of real world practices. Therefore we studied GA in elderly MM patients consecutively in China, along with other perspectives which are known to be problematic in elderly population that were previously left unnoticed, such as nutrition status, risk of cognitive impairment, risk of depression, and quality of life. Aim: Our study centers on the feasibility to perform a more comprehensive geriatric assessment (cGA) in elderly MM patients, current cGA status in elderly MM patients in China, and the cGA difference between Chinese patients and patients in the IMWG study. Method: From August 2017 to April 2019, we continuously recruited 336 newly diagnosed elderly (age ≥ 65) MM patients from 21 centers in China. cGA was performed at diagnosis, after treatment cycle 1, after cycle 4, and 1 year after treatment. cGA includes physical conditions (ECOG), activities of daily living (ADL), instrumental ADL (IADL), mini-nutritional assessment (MNA-SF), geriatric depression scale (GDS), mini-mental state examination (MMSE), quality of life (SF-36) and Charlson comorbidity index (CCI). Staging was assessed at baseline (International Staging System (ISS) & Revised ISS) and hematological responses were evaluated along with each cGA timepoint. Results: We pool-analyzed data of 336 newly-diagnosed elderly MM patients. The median age was 70 (range 65-88) and 25.5% of patients were older than 75 years. 336 (100%) patients were able to complete cGA, and median assessment time was 40 minutes (range 20-70). Upon diagnosis, only 34% and 37.5% of patients had full ADL and IADL respectively. 38.5% of patients had moderate to high risk of depression (GDS ≥ 6). 13.2% of patients were malnourished (MNA-SF ≤ 7), while 46.3% of patients were at risk of malnutrition (8 ≤ MNA-SF ≤ 11). 41% of patients had at least one comorbidity (CCI ≥ 1). 45.7% of patients had moderate to intermediate risk of cognitive impairment (MMSE ≤ 26). Grouping by IMWG-GA index, our study identified 59.9% patients in frail group (vs 39% in IMWG study), 15.8% in intermediate (vs 31% in IMWG) and 24.3% in fit (vs 30% in IMWG). 69% of patients received proteasome inhibitor-containing regimens and 20.7% of patients received lenalidomide-containing regimens. Best hematological responses in fit and intermediate groups were better than responses in frail group (≥ PR rate: 88.5% in fit, 94.4% in intermediate vs 77.5% in frail). Median follow up time was 10 months. To date, 215 (64%) patients have finished the cGA after cycle 1; 164 (48.8%) patients have finished the cGA after cycle 4; 91 (27.1%) patients has finished all 4 planned cGA and improvements in cGA were observed in the majority of these patients. Conclusion: Our study showed significant CGA heterogeneity in elderly MM patients. Even in the IMWG-GA "fit" group, nutrition, depression and cognitive impairment remain problems. Frail patients took up a larger proportion in Chinese elderly MM patients compared to IMWG study. Our study strongly justifies the necessity for cGA in elderly patients with MM, more so in the real world MM patients than in the clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinicians’ experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
N. Carlisle ◽  
H. A. Watson ◽  
J. Carter ◽  
K. Kuhrt ◽  
P. T. Seed ◽  
...  
Keyword(s):  
Decision Making ◽  
Preterm Birth ◽  
Cultural Context ◽  
Clinical Decision Making ◽  
Qualitative Interviews ◽  
Scale Up ◽  
Clinical Decision ◽  
Clinical Trial Registry ◽  
Support Tool ◽  
The Impact

Abstract Background As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth. Methods Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians’ (obstetricians’ and midwives’) experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach. Results Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: ‘experience of using the app’, ‘how QUiPP risk changes practice’ and ‘successfully adopting QUiPP: context is everything’. With these final themes we appeared to have achieved our aim of exploring the clinicians’ experiences of using and implementing the QUiPP app. Conclusion This study explored different clinician’s experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL. Clinical trial registry and registration number ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337.

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document