scholarly journals Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Date in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyan Han ◽  
Chunxiang Jin ◽  
Gaofeng Zheng ◽  
Donghua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Maintenance Therapy ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
Patient Responses

IntroductionWe analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients.MethodsA total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed.ResultsThe maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2–3, DS 2–3, and RISS 2–3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292).ConclusionPIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.

scholarly journals Proteasome Inhibitor or Immunomodulators Which is The Optimal Maintenance For Newly Diagnosed Multiple Myeloma: A 7-Year Real-World Data in China.

2021 ◽  
Author(s):  
Xiaoyan Han ◽  
Chunxiang Jin ◽  
Gaofeng Zheng ◽  
Donghua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Maintenance Therapy ◽  
Proteasome Inhibitor ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Real World Data ◽  
High Risk Patients ◽  
Optimal Maintenance ◽  
Risk Patients

Abstract Background: According to different patients’ subgroups choose optimal maintenance therapy. Methods: 226 Newly Diagnosed Multiple Myeloma (NDMM) patients in our center were included, the patients’ characteristics, survival, response, subgroup analysis, adverse reactions were compared between the patients with or without maintenance, proteasome inhibitor (PI) or immunomodulators (IMiDs) maintenance. And the survival of different maintenance duration of bortezomib-based regimens was also analyzed.Results: The maintenance therapy not only upgraded more patients’ response (34.3 vs. 13.3%, p= 0.006), but also significantly prolonged the patients’ PFS (median PFS: 41.1 vs. 10.5 months, p < 0.001) and OS (median OS: not reached vs. 38.6 months, p < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs. 38.5 months, p = 0.034) and OS (median OS: not reached vs. 78.5 months, p = 0.041) can both benefit from bortezomib-based maintenance. The patients younger than 65 years old with bortezomib-based maintenance significantly prolonged the OS (p= 0.032). Patients achieving the only partial response (PR) after induction and consolidation therapy experienced a significantly longer PFS and OS with bortezomib-based maintenance compared to IMiDs (p= 0.007, 0.002). Besides, the high-risk patients (ISS 2-3, DS 2-3 and RISS 2-3) with bortezomib-based maintenance can benefit PFS (p= 0.002, 0.02, 0.06, respectively) and OS (p=0.059, 0.047, 0.044, respectively) compared with IMiDs. The OS was significantly prolonged in the patients who received ≥12 months of bortezomib-based maintenance than those with maintenance < 12 months (p< 0.001), but no difference was observed in OS between the patients who received the 12-24 or ≥ 24months of bortezomib-based maintenance (p= 0.292).Conclusion: Maintenance therapy can significantly improve the survival of NDMM patients. Bortezomib-based regimens maintenance was more superior to IMiDs in overall PFS and OS. The beneficial effect is most evident in patients achieving the only PR after induction and consolidation therapy, and the high-risk patients. Moreover, younger patients also could benefit from bortezomib-based maintenance in OS. The bortezomib-based maintenance duration lasting 12-24 months after induction and consolidation therapy can reach a satisfactory OS.

Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance

Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4547-4553 ◽  
Author(s):  
María-Victoria Mateos ◽  
Norma C. Gutiérrez ◽  
María-Luisa Martín-Ramos ◽  
Bruno Paiva ◽  
María-Angeles Montalbán ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Dna Ploidy ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
High Risk Patients ◽  
Risk Patients ◽  
Standard Risk

Abstract Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.

scholarly journals The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110196
Author(s):  
Albert Oriol ◽  
Laura Abril ◽  
Anna Torrent ◽  
Gladys Ibarra ◽  
Josep-Maria Ribera
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Safety Profile ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Acceptable Safety Profile ◽  
Refractory Multiple Myeloma ◽  
High Risk Patients ◽  
Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

scholarly journals Lenalidomide Compared to Ixazomib Maintenance in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3776-3776
Author(s):  
Eunice Lai ◽  
Yu Yang Soon ◽  
Ainsley Ryan Yan Bin Lee ◽  
Shi Yin Wong ◽  
Cinnie Yentia Soekojo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Meta Analysis ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Risk Of Bias ◽  
Newly Diagnosed ◽  
Maintenance Strategies

Abstract Background Maintenance therapy is considered a standard of care in transplant eligible (TE) and non transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM). While immunomodulators (IMID) and proteasome inhibitors (PI) have been proposed as maintenance therapy options, there are no randomised trials (RCTs) directly comparing these agents in the maintenance setting. The IMID lenalidomide (Len) and the PI ixazomib (Ixa) have been compared against placebo as maintenance strategies in NDMM. We present a network meta-analysis (NMA) of RCTs comparing the efficacy and safety of Len and Ixa maintenance therapies in NDMM. Methods We searched various biomedical databases for eligible studies evaluating Len or Ixa against placebo/ observation as maintenance therapy in patients with NDMM from date of inception through November 2020. The primary outcome was progression-free survival (PFS). Secondary outcomes include overall survival (OS) and adverse events (AE). The Cochrane risk of bias tool version 2.0 was used to assess trial quality. A Bayesian NMA model was used to assess the relative effects of competing treatments on PFS and OS outcomes. Adverse events were assessed using the synthesis without meta-analysis (SWIM) approach due to variability in the toxicity scoring criteria. The GRADE approach was used to rate the certainty of the evidence. This study is registered with PROSPERO, CRD42021226157. Results We identified eight studies including 3229 transplant eligible (TE) and 1689 non transplant eligible (NTE) patients. All studies were judged to have low risk of bias. Len but not Ixa was associated with statistically significant improvement in PFS when compared to placebo in TE (Len: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.35-0.56, high certainty; Ixa: HR 0.72, 95% CrI 0.46-1.13, moderate certainty) and NTE (Len: HR 0.46, 95% CrI 0.29-0.75, high certainty; Ixa: HR 0.69, 95% CrI 0.43-1.18, moderate certainty). Bayesian modelling demonstrated a 97% and 93% probability that Len resulted in superior PFS compared to Ixa in TE and NTE patients respectively. Both Len and Ixa were not associated with statistically significant improvement in OS compared to placebo in TE and NTE patients. There was no significant effect modification on the effect of Len vs placebo and Ixa vs placebo by cytogenetics status, use of proteasome inhibitors for induction or duration of maintenance therapies for PFS and/or OS outcomes. Len were judged to have a higher incidence of second malignancies and grade 3 or 4 neutropenia than Ixa while Ixa was judged to have a higher incidence of thrombocytopenia than Len. Conclusions Maintenance therapy with Len may provide a larger PFS benefit than Ixa regardless of type of induction therapy and cytogenetic risk in patients with NDDM. The differing toxicity profile of these agents is also an important consideration for treatment decisions. RCTs directly comparing these maintenance strategies are warranted. Figure 1 Figure 1. Disclosures Ooi: Jansen: Honoraria; Teva Pharmaceuticals: Honoraria; GSK: Honoraria; Abbvie: Honoraria; Amgen: Honoraria. Chng: Sanofi: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria, Research Funding; Pfizer: Honoraria.

GIMEMA-AIEOP AIDA Protocols for the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (APL) In Children: Analysis of 247 Patients Enrolled In Two Sequential Italian Multicenter Trials

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 871-871 ◽  
Author(s):  
Anna Maria Testi ◽  
Robin Foa ◽  
Gabriella Tomei ◽  
Francesco Lo Coco ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 871 Since 1993, Italian pediatric patients (age <18 years) with newly diagnosed acute promyelocytic leukemia (APL) have been enrolled in two consecutive multicenter Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) - Italian Pediatric Hematology and Oncology Group (AIEOP) AIDA 0493 and 2000 trials. The AIDA 0493 protocol consisted of an induction including ATRA (25 mg/m2/day) and idarubicin, followed by three polychemotherapy consolidation courses without ATRA and a four-arm randomized maintenance therapy for patients who were PCR- after consolidation. The AIDA 2000 trial, which started in September 2000, included the same induction followed by a risk-adapted (Sanz criteria, Blood 2004) consolidation. Low and intermediate risk children received three less intensive anthracycline-based courses plus ATRA; for high risk patients, consolidation was intensified by adding ATRA to the three polychemotherapy consolidation courses of the previous protocol. Maintenance therapy consisted of standard daily mercaptopurine and weekly methotrexate given for two years. ATRA was administered for fifteen days every three months during all maintenance therapy. Between January 1993 and June 2000, 124 children were enrolled in the AIDA 0493 protocol. The results of this study have been previously reported (Testi et al, Blood 2005). From July 2000 to January 2009, 123 children with newly diagnosed APL were enrolled in the AIDA 2000 risk-adapted trial. We have now performed an updated analysis of the results of the first study and compared these results with those achieved with the AIDA 2000 study. The median follow-up is 12 and 5 years for the AIDA 0493 and 2000 studies, respectively. No differences in the main clinical and biologic diagnostic patients' characteristics - M/F ratio, median age, median WBC count, FAB M3/M3v, BCR1/BCR2/BCR3, low-intermediate/high risk - were observed between the two groups; the median platelet count was higher in the AIDA 2000 group (27.5 vs 20 × 109/L, p 0.05). The complete remission rate was 96% and 100% in the AIDA 0493 and 2000 protocols, respectively, with no patient showing resistant disease. No toxic death was recorded during the consolidation phase in both protocols; at recovery from the third consolidation course, 97% and 99% of the two groups of patients, tested by RT-PCR, achieved molecular negativity. The 6-year Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) are 89.7% (CI 95%: 84.7–95) vs 96% (CI 95%: 91.7–100), (p 0.05) and 73.1% (CI 95%: 66.7–80.2) vs 82.5% (CI 95%: 75.9–89.8), (p 0.28) in the AIDA 0493 and 2000 protocols, respectively. For low/intermediate risk children, OS and DFS at 6 years are 94.2% (CI 95%: 89.1–99.5) and 76.7% (CI 95%: 68.9–85.4) in the AIDA 0493 vs 95.6% (CI 95%: 90.0–100) and 82.7% (CI 95% 74.9–91.3) in the AIDA 2000 trial, respectively (p 0.57 and 0.73); considering high risk patients, OS and DFS at 6 years are 81.6% (CI 95%: 72.1–92.3) and 65.2% (CI 95%: 54.7–77.6) in the AIDA 0493 vs 96.8% (CI 95%: 90.9–100) and 82.3% (CI 95%: 70.1–96.5) in the AIDA 2000 trial (p 0.05 and 0.20). These results confirm the high anti-leukemic efficacy of the ATRA + idarubicin induction combination. For low/intermediate risk children, the anthracycline-based plus ATRA consolidation is equally effective as the previous cytarabine-containing regimen. The risk-adapted strategy including ATRA for consolidation resulted into a significant improvement in OS for all children. Furthermore, our results highlight the role of cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group. Disclosures: Foa: Roche: Consultancy, Speakers Bureau.

Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia: Results From a Randomized Controlled Trial

2014 ◽  
Vol 32 (33) ◽  
pp. 3729-3735 ◽  
Author(s):  
Katsuji Shinagawa ◽  
Masamitsu Yanada ◽  
Toru Sakura ◽  
Yasunori Ueda ◽  
Masashi Sawa ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Controlled Trial ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
High Risk Patients ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
Wbc Count

Purpose The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. Patients and Methods Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. Results A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 109/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non–high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. Conclusion In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.

scholarly journals Dose-dense and less dose-intense Total Therapy 5 for gene expression profiling-defined high-risk multiple myeloma

2016 ◽  
Vol 6 (7) ◽  
pp. e453-e453 ◽  
Author(s):  
Y Jethava ◽  
A Mitchell ◽  
M Zangari ◽  
S Waheed ◽  
C Schinke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
High Risk ◽  
Progression Free Survival ◽  
Drug Dosing ◽  
High Risk Patients ◽  
Major Predictor ◽  
Risk Patients ◽  
Total Therapy ◽  
Dose Dense

Abstract Multiple myeloma (MM) is a heterogeneous disease with high-risk patients progressing rapidly despite treatment. Various definitions of high-risk MM are used and we reported that gene expression profile (GEP)-defined high risk was a major predictor of relapse. In spite of our best efforts, the majority of GEP70 high-risk patients relapse and we have noted higher relapse rates during drug-free intervals. This prompted us to explore the concept of less intense drug dosing with shorter intervals between courses with the aim of preventing inter-course relapse. Here we report the outcome of the Total Therapy 5 trial, where this concept was tested. This regimen effectively reduced early mortality and relapse but failed to improve progression-free survival and overall survival due to relapse early during maintenance.

Prospective study to measure the impact of MMprofiler on treatment intention in newly diagnosed multiple myeloma patients (PROMMIS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8030-8030
Author(s):  
Parameswaran Hari ◽  
Suzanne Lentzsch ◽  
David Samuel DiCapua Siegel ◽  
Saad Zafar Usmani ◽  
Binod Dhakal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Risk Classification ◽  
Newly Diagnosed ◽  
Treatment Paradigm ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

8030 Background: Multiple Myeloma (MM) is recognized as a heterogeneous group of patients with varying response and outcome of their disease, associated with various risk factors including genetic aberrations. Risk adapted treatment strategies are beginning to emerge (e.g. mSMART), which include gene expression signatures. SKY92, a 92-gene prognostic signature, classifies MM patients as “high” or “standard” risk. It has been reported to be a robust predictor for Overall and Progression Free Survival (Kuiper 2012, 2015). Here we report the preliminary impact of SKY92 on risk classification and treatment intention decisions in newly diagnosed MM patients enrolled in the PRospective Observational Multiple Myeloma Impact Study (PROMMIS). Methods: Patients with MM had their BM aspirate analyzed using the MMprofiler with SKY92. The physician completed questionnaires with his/her treatment intention, before and after knowing SKY92 results. Results: 39 MM patients were enrolled from 5 US centers. The SKY92 signature classified 15 patients (38%) as high risk. Prior to knowing SKY92 results, physicians regarded 20 (51%) patients as clinically high risk, for whom SKY92 indicated 12 patients to be standard risk. Upon revealing SKY92, 8 patients were then considered standard risk by the physician. For 2 patients with concordant high risk classification results, the confirmation of the risk classification was considered helpful. The impact of treatment intention decisions in clinical high risk patients was 40% (8 out of 20). In the 19 patients (49%) that were regarded clinically standard risk prior to knowing SKY92, SKY92 indicated 7 patients to be high risk. Physicians agreed to this classification. For 4 patients with concordant risk classification, the confirmation was found helpful. The impact of treatment intention decisions in clinical standard risk patients was 37% (7 out of 19). Conclusions: Preliminary results from the PROMMIS trial indicate that SKY92 impacts the physician’s treatment intention for 38% of patients with newly diagnosed MM. Moreover, the physicians found the SKY92 result useful for 54% of the patients. This underlines the relevance and need for assessment of SKY92 in MM patients, and associated risk stratified treatment paradigm. Clinical trial information: NCT02911571.

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