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.

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 &lt; 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P &lt; 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 &lt; 12 months (P &lt; 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.

Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Eric Leon Tam ◽  
David Joseph Iberri ◽  
Michaela Liedtke ◽  
Lori S. Muffly ◽  
Parveen Shiraz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Maintenance Therapy ◽  
Proteasome Inhibitor ◽  
Post Transplant ◽  
Risk Patients ◽  
To Receive ◽  
Standard Risk

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p < 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]

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.

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.

Updates on safety and efficacy of maintenance therapy after autologous stem cell transplantation in newly diagnosed multiple myeloma: A systematic review.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20503-e20503
Author(s):  
Ahsan Wahab ◽  
Kamran Mushtaq ◽  
Maria Khakwani ◽  
Aqsa Khan ◽  
Afia Ashraf ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Combination Therapy ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
High Risk Patients ◽  
Risk Patients ◽  
Dose Reductions

e20503 Background: Multiple Myeloma (MM) is treatable but an incurable hematological malignancy, requiring additional approaches such as maintenance therapy (MT) after autologous-stem cell transplantation. MT aids to achieve deepened response, sustained response and prolongs progression-free survival (PFS) but has a controversy over its overall survival (OS) benefit. Within the last decade, there have been innovative efforts tested for MT. We designed a systematic review to evaluate the current evidence on this topic. Methods: PubMed and Embase were searched for articles published on MT between 01/2010 and 12/2018 and PRISMA guidelines were used to evaluate 76,588 articles on PubMed and 1516 articles on Embase. Thirty-three articles were included in systematic review. Results: Thirteen articles were available on lenalidomide-MT whereas six articles each on thalidomide and proteasome inhibitors, five articles on combination therapy, two articles on miscellaneous and one article on elotuzumab were available, including trials and observational studies. MT (thalidomide 50 mg, lenalidomide 10 mg) was given for a variable period, commonly used till relapse, progression or unacceptable toxicity. Thalidomide showed consistent PFS-benefit but no OS benefit and had significant neurotoxicity, responsible for discontinuations or dose reductions. Lenalidomide had evidence for both, improved PFS and some evidence for better OS and had hematotoxicity, mainly neutropenia which required dose reductions. Secondary primary malignancies were more frequent with lenalidomide. Longer maintenance of lenalidomide was associated with more toxicity. Thalidomide-bortezomib combination had better PFS than thalidomide alone but no OS benefit. Bortezomib-MT improved OS in high-risk patients and renal failure and had dose-dependent toxicity. Bortezomib-MT after bortezomib-based induction was better than thalidomide-based-MT after cytotoxic induction. MT was associated with the achievement of negative MRD-status. Ixazomib was effective and feasible with improved PFS. Combination of bortezomib-lenalidomide-dexamethasone MT was beneficial in high-risk patients. Conclusions: MT improves PFS with limited evidence toward improved OS. For better outcomes, lenalidomide-based-MT should be given routinely; adjustment of dose might be required due to neutropenia. High-risk patients can get benefit from combination therapy. Role of combination MT needs to be further explored in large prospective studies.

Risk-Adapted Treatment of Acute Promyelocytic Leukemia: Results of the PETHEMA LPA2005 Trial Using All-Trans Retinoic Acid and Anthracycline with Cytarabine for High-Risk Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 138-138 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Aleksandra Holowiecka ◽  
Gustavo Milone ◽  
Chelo Rayon ◽  
...  
Keyword(s):  
High Risk ◽  
Synergistic Effect ◽  
Maintenance Therapy ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Low Risk ◽  
Consolidation Therapy ◽  
Triple Combination ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background: A previous report of the PETHEMA Group (Sanz et al, Blood 2004) showed that a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for induction and consolidation (LPA99 trial), followed by ATRA and low dose methotrexate and mercaptopurine for maintenance therapy, resulted in high antileukemic efficacy, moderate toxicity, and a high degree of compliance. A critical analysis of this study led us to consider the following opportunities for improvement in a new trial: the observation of a lack of relapses in non high-risk patients (WBC counts &lt;10 × 109/L) who had received incomplete consolidation therapy due to the occurrence of severe complications, led us to consider that there was room for a reduction of chemotherapy in this potentially overtreated setting; the outstanding results reported by the Italian GIMEMA Group in high-risk patients &lt; 60 years combining ATRA, anthracycline and cytarabine in consolidation (Lo- Coco et al, ASH 2004) led us to investigate a similar strategy looking for a synergistic effect of this triple combination of drugs. Thus, a new risk-adapted PETHEMA trial (LPA 2005) was designed and initiated in July 2005. Methods: AIDA regimen (ATRA 45 mg/m2/d ATRA until CR and idarubicin 12 mg/m2/d on days 2, 4, 6 and 8) was given as induction therapy. Patients in CR received 3 monthly courses of risk-adapted consolidation therapy as follows: i.”low-risk” patients (WBC &lt;10×109/l and platelets &gt;40×109/l) received ATRA (45 mg/m2/d × 15) simultaneously with idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 3 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3); ii.”intermediaterisk” patients (WBC &lt;10×109/l and platelet &lt;40×109/l) received ATRA (45 mg/m2/d × 15) in combination with reinforced chemotherapy (idarubicin 7 mg/m2/d in the course #1 and 2 days instead of 1 in the course #3). Both risk groups received mitoxantrone × 3 in course #2 instead of × 5 in the LPA99 trial; and iii.”high-risk” patients (WBC &gt;10×109/l) &lt; 60 years received ATRA (45 mg/m2/d × 15) and idarubicin in courses #1 and #3 at the same dose than for low-risk patients but with the addition of cytarabine (1000 mg/m2/d × 4 in course #1 and 150 mg/m2/8 h days 1 to 4 in course #3) and 2 more days of mitoxantrone in course #2 (5 days instead of 3). Maintenance therapy consisted of 50 mg/m2/d mercaptopurine orally, 15 mg/m2/week methotrexate intramuscularly, and 25 mg/m2/d ATRA for 15 days every three months during 2 years. Results: Of 319 patients enrolled in the LPA 2005 trial between July 2005 and July 2008, data on baseline characteristics and induction outcome was available from 290 patients. CR was achieved in 268 patients (92%). No resistant cases were observed. Toxicity was manageable during consolidation and there were 2 deaths in CR during consolidation. The median follow-up of the cohort was 21 months (range, 2–38). Six patients presented hematological relapse and 3 molecular relapse. Overall, the 2-year cumulative incidence of relapse (CIR), disease-free survival, and overall survival were 5%, 94%, and 92%, respectively. The 2-year CIR for low-, intermediate- and high-risk patients were 0%, 6% and 8%, respectively. A comparison of these results with those obtained with the LPA99 trial show a statistically significant lower CIR in high-risk patients (p=0.047). Conclusions: The significant improvement of the outcome observed in high-risk patients suggests a synergistic effect of the triple combination of ATRA, anthracycline and cytarabine.

Sign in / Sign up

Export Citation Format

Share Document