scholarly journals Lenalidomide and Low Dose Dexamethasone Plus Elotuzumab or Carfilzomib for Relapsed or Refractory Multiple Myeloma: A Comparison of Progression-Free Survival with Reconstructed Individual Participant Data

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shuo Li ◽  
Xiang-Yu Meng ◽  
Souraka Tapara Dramani Maman ◽  
Yong-Nong Xiao ◽  
Sheng Li
Keyword(s):  
Multiple Myeloma ◽  
Survival Analysis ◽  
Low Dose ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Baseline Status ◽  
Individual Participant

Background. Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports. Methods. We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated. Results. Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67]). Conclusion. The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.

Immunologic Recovery after Autologous Transplant in Multiple Myeloma and Progression Free Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4444-4444
Author(s):  
Fernanda Maria Rodrigues Trigo-Miranda ◽  
Rui Cordeiro Bergantim ◽  
Ricardo Moreira Pinto ◽  
Patricia Guimarães ◽  
Jose E. Guimaraes
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Cell Transplant ◽  
Haematopoietic Progenitor Cell ◽  
Free Survival ◽  
Post Transplant ◽  
Historical Comparison ◽  
Significant Difference

Abstract Several factors influencing disease progression and survival have been identified in multiple myeloma (MM). We analysed a series of 49 consecutive patients with MM that underwent autologous haematopoietic progenitor cell transplant (HPCT) in one center regarding the following variables: use of G-CSF for haematopoietic recovery post-transplant; recovery of normal IgM levels at day +100 post-transplant; levels of lymphocytes namely of the CD4+ and CD8+ subsets also at day +100. Before 2006, all patients had G-CSF starting 24 hours after the cell infusion until neutrophil &gt; 500×10^9/L in two consecutive days; in the years 2006–2008, no G-CSF was given to transplanted patients. A historical comparison was done and at the time of this study no significant difference in progression free survival (Kaplan-Meyer analysis), was detected between the two groups, possibly due to the shorter follow-up of the “no G-CSF” (n=19) group; nevertheless median progression free survival (PFS) in the “G-CSF” group was 12 months while median PFS was not attained in the “no G-CSF” group (median follow-up = 7 months). Post transplant IgM levels were also determined in 39 patients. Eighteen patients recovered normal IgM levels at day +100 (46.8 %) and 21 (53.8 %) did not. Comparison of Kaplan-Meyer curves for the two groups did not show any statistically significant difference but there is a sharp difference between median PFS of the “low IgM” (10 months) and the “normal IgM” (27 months) groups. CD4/CD8 ratio was determined in 18 patients at day +100. The ratio varied between 0 and 0.63 (median – 0.305). No correlation was found between post-transplant IgM recovery and CD4/CD8 ratio. In conclusion, in our series of MM patients treated with autologous HPCT we could not find a definite relationship between immunologic recovery and response to treatment although there is a trend to a better outlook of the patients which recover normal IgM levels. It is also uncertain whether use of G-CSF in the post-transplant period would have any effect on disease behaviour.

scholarly journals Hosszú távú progressziómentes túlélés relabált, refrakter myeloma multiplex tisztán orális ixazomib-lenalidomid-dexametazon kezelésével

2021 ◽  
Vol 162 (36) ◽  
pp. 1451-1458
Author(s):  
Apor Hardi ◽  
Gergely Varga ◽  
Zsolt Nagy ◽  
Szabolcs Kosztolányi ◽  
László Váróczy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Staging System ◽  
Term Therapy ◽  
Sustained Remission ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier

Összefoglaló. Bevezetés: A myeloma multiplex mindmáig alapvetően gyógyíthatatlan betegség, ezért nagy klinikai jelentőségük van az eredményes mentő kezeléseknek. A szájon át adható első proteaszómagátlóval, az ixazomibbal kiegészített lenalidomid-dexametazon terápia jól tolerálható, csak orális szerekből álló kombináció, mely hazánkban 2015 áprilisától kezdődően a „Named Patient Program” keretén belül vált elérhetővé relabált, refrakter myeloma multiplexes betegek kezelésére. Célkitűzés: Kutatásunk célja az ixazomib-lenalidomid-dexametazon kezelés mellett a hosszú távon progressziómentes túlélők célzott vizsgálata. Módszer: A program keretében összesen 7 centrumban 80 visszaeső beteg részesült e triplet kezelésben, adataikat retrospektíven elemeztük. Leíró statisztikai és Kaplan–Meier-analízist végeztünk. Eredmények: A betegek nagyobb hányada reagált: 63,75%-os válaszarány mellett 14 (17,5%) betegnél nem volt terápiás válasz/stabil betegség alakult ki, és 15-nél (18,75%) a betegség a kezelés mellett is progrediált. A progressziómentes túlélés a teljes betegcsoportban 10,6 hónapnak adódott, ugyanakkor 16 beteg (18,75%) két éven túl progressziómentesnek bizonyult, sőt közülük 11-nél a betegség még 3 év után sem progrediált. Tanulmányunkban a fenti, hosszú távú túlélő betegcsoport tulajdonságait tárjuk fel. Megbeszélés: A folyamatos terápia a myeloma multiplex kezelésében meghatározóvá vált. Ezért fontos ismernünk, hogy kik lehetnek azok a betegek, akik különösen sokat profitálnak egy bizonyos terápiából. A hosszú távon progressziómentes túlélők között az immunglobulin-nehézláncot érintő transzlokációk vagy triszómiák közül (trend szintjén) az utóbbiak kedvezőbb progressziómentes túléléssel bírtak, de progressziómentes platót mindkét betegcsoportban észleltünk. A betegség tumortömegét mérő nemzetközi stádiumbeosztás (ISS) nem jelezte előre a hosszú túlélést. Gyógyszerelhagyáshoz vezető mellékhatást a hosszú távú túlélő csoportban egyet sem regisztráltunk; az észlelt mellékhatások nagy része enyhe volt. Következtetések: Munkánk során az ixazomib-lenalidomid-dexametazon kombinációt effektívnek és biztonságosnak találtuk relabált, refrakter myeloma multiplex kezelésére, mely a betegek mintegy hatodánál több éven át eredményesen alkalmazható. Cikkünkkel a hazai beteganyagon szerzett tapasztalatainkat szeretnénk megosztani a COVID–19-világjárvány alatt különösen aktuálissá vált, tisztán orális terápiás lehetőségről. Orv Hetil. 2021; 162(36): 1451–1458. Summary. Introduction: Despite great advances in therapy, multiple myeloma is still a largely incurable disease, therefore the importance of salvage therapies is paramount. The first oral proteasome inhibitor ixazomib in combination with lenalidomide-dexamethasone is a tolerable, orally administered regime, which has become available for Hungarian relapsed, refractory multiple myeloma patients from April 2015 in the Named Patient Program. Objective: Our goal was to investigate the long-time progression-free surviving patient population treated with the ixazomib-lenalidomide-dexamethasone triplet. Method: We retrospectively studied a total of 80 patients from 7 centers who received the triplet combination. Survival analyses were performed. Results: Two-third of the patients responded: the overall response rate was 63.75%. 14 patients (17.5%) did not respond/had stable disease and 15 patients (18.75%) outright progressed upon therapy. Although progression-free survival was only 10.6 months for the entire patient cohort, the disease in a subgroup of 16 patients did not progress within two years. In fact, 11 of them were still in sustained remission after 3 years of therapy. Our goal was to analyze the characteristics of this subgroup. Discussion: The idea of long-term therapy of multiple myeloma is gaining widespread acceptance. Therefore it is important to know which patients may benefit the most from certain therapies. Among these 16 long-term responder patients, reciprocal translocation of the immunoglobulin heavy chain seemed to lack an adverse impact on progression-free survival; comparable to trisomies, both curves had a progression-free plateau. The International Staging System (ISS) score at the start of therapy did not predict long-term survivorship. Most of the side effects in this subgroup were mild, manageable, none led to therapy discontinuation. Conclusion: Ixazomib-lenalidomide-dexamethasone was confirmed to be an effective and safe combination for relapsed, refractory multiple myeloma, and one-sixth of the treated patients were able to receive it for several years, effectively. This fully oral therapeutic option is at its best during the present COVID–19 pandemic. Orv Hetil. 2021; 162(36): 1451–1458.

scholarly journals Adverse events during immunotherapy in Slovenian patients with metastatic melanoma reveal a positive correlation with better treatment outcomes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tanja Mesti ◽  
Vid Ceplak Mencin ◽  
Biljana Mileva Boshkoska ◽  
Janja Ocvirk
Keyword(s):  
Survival Analysis ◽  
Adverse Events ◽  
Treatment Outcomes ◽  
Metastatic Melanoma ◽  
Survival Probability ◽  
Progression Free Survival ◽  
Cox Proportional Hazards Model ◽  
Free Survival ◽  
Overall Response ◽  
Significant Difference

Abstract Background Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy. Patients and methods A retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups. Results Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE cohort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort. Conclusions Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall response rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.

scholarly journals Unmanipulated Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Post Transplant Cyclophosphamide Anti-Gvhd Prophylaxis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3475-3475 ◽  
Author(s):  
Luca Castagna ◽  
Alberto Mussetti ◽  
Raynier Devillier ◽  
Alida Dominietto ◽  
Magda Marcatti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Kaplan Meier ◽  
Gvhd Prophylaxis

Abstract Backgrounds: Allogeneic Hematopoietic Cell Transplantation (HCT) is a potentially curative treatment for fit patients with relapsed/refractory multiple myeloma (MM). When a HLA-identical donor is not available, haploidentical HCT (haploHCT) represents an acceptable therapeutic option, especially when post-transplant cyclophosphamide (PT-Cy) is used as anti-GVHD prophylaxis. Patients and methods: Twenty-nine patients (median age 56 years, range 47-70) undergoing myeloablative (n=15) or reduced-intensity (n=14) haploHCT from February 2011 to November 2015 are included in this retrospective analysis. The median number of previous lines of therapy was 2 (range 1-7) with 27 (93%) of patients having previously performed an autologous HCT. Both bortezomib and lenalidomide were used in 27 (92%) patients before haploHCT. Eighteen patients (62%) had chemosensitive disease at time of haploHCT (CR=4, VGPR=9, PR=5) and 11 (38%) had chemorefractory disease (PD=7, SD=4). Graft source was marrow-derived in 59% (n=17) and peripheral blood in 41% (n=12) of patients. Standard post-transplant cyclophosphamide anti-GVHD prophylaxis (50mg/mq day +3 and +4 or +5) plus mycophenolate and cyclosporine (n=24) or tacrolimus (n=3) or rapamycine (n=2) was used for the whole study cohort. Overall survival (OS) and Progression Free Survival (PFS) were performed with Kaplan-Meier analysis. Neutrophil and platelets engraftment, acute GVHD, chronic GVHD, Non-Relapse-Mortality (NRM) and Relapse Incidence/Progression of Disease (RI/POD) were obtained with competing risk analysis. Results: At day +30, neutrophil and platelets engraftments were 86% (95%CI:65-95) and 59% (95%CI:38-74), respectively. Acute GVHD grade >2 at days +100 and +180 were 38% (95%CI: 20-55%) and 41% (95%CI: 23-59%), respectively. All grade chronic GVHD at 12 and 18 months was 21% (95%CI: 8-37. At 18 months, RI/POD was 39% (95%CI:20-58%) and NRM 15% (CI95%:5-32). With a median follow-up in survivors of 16 months (range 5-55 months), the 18-month OS and PFS were 68% (95%CI: 47-82%) and 34% (95%CI: 15-54%), respectively. Chemorefractory disease at transplant was associated with a worse 18-month RI/POD (70% vs 18%, p=<0.01) and a markedly reduced PFS (9% vs 57%, p=0.04) and OS (53% vs 78%, p=<0.01) (Figure 1). Survival outcomes were similar between marrow-derived and peripheral blood graft source cohorts. Conclusions: HaploHCT is a feasible and effective strategy in patients with relapsed/refractory high-risk multiple myeloma. Chemorefractory disease at transplant was the only prognostic factor associated with a significant reduced RI/POD, PFS and OS. Figure Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease. Figure. Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease. Disclosures No relevant conflicts of interest to declare.

Efficacy and safety of radiotherapy (RT) plus temozolomide (TMZ) in elderly patients (EP) with glioblastoma (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2043-2043 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Luisa Bellu ◽  
Franco Berti ◽  
Patrizia Farina ◽  
Sara Galuppo ◽  
...  
Keyword(s):  
Haematological Toxicity ◽  
Progression Free Survival ◽  
Severe Toxicity ◽  
Wild Type ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Grade 3 ◽  
Ecog Ps

2043 Background: the optimal management of EP with GBM remains controversial. The role of RT with TMZ for EP is unclear, and EP are often treated with RT alone, TMZ alone or palliative approaches. We describe our experience of combining RT with concurrent TMZ for treatment of EP with GBM Methods: medical records of patients ≥65 years old with newly GBM, histologically confirmed at Veneto Institute of Oncology – Padua, and treated with RT plus TMZ, were reviewed. Concomitant TMZ was 75mg/m2/die. The adjuvant treatment consisted of TMZ 150-200mg/m2/die for six cycles. Median progression-free survival(PFS) and overall survival(OS) were estimated with Kaplan-Meier method. Toxicity was scored according to CTCAE 4.0 Results: we analyzed 60 patients(PTS), 34 males and 26 females; the average age was 70 (range 65-82); ECOG PS was 0-1 in 35 PTS and 2 in 25 PTS; complete surgery was performed in 35 PTS, partial surgery in 25 PTS. 40 and 20 PTS received RT within 6 or more weeks (range 7-9) from surgery. MGMT and IDH1 were analyzed in 43 PTS: MGMT methylated in 20 PTS (46%), all PTS had wild-type IDH1. 34 PTS were treated with RT 40Gy in 15 fractions, 26 PTS with RT 60Gy in 30 fractions with no significant difference in ECOG PS, MGMT and type of surgery between the two subgroups. For all PTS, PFS and OS were 9.5 and 12.7 ms, respectively. OS was 13.7 and 12.4 ms (p=0.9) in PTS receiving RT within 6 or more weeks from surgery, respectively. 13% of PTS showed grade 3-4 haematological toxicity, 12% grade 3-4 asthenia, 3% nausea/vomiting. MGMT methylated and complete surgery was associated with a longer survival. PFS was 9 vs 10 months (p=0.4) and OS was 11.7 vs 13.7 ms (p=0.1), for PTS treated with 40Gy and 60Gy, respectively. Regarding toxicity: grade 3-4 haematological toxicity was 9% vs 23%, severe asthenia was 9% vs 15%, nausea/vomiting was 3% vs 4% of PTS receiving RT 40Gy and 60Gy, respectively. Conclusions: RT plus TMZ is effective and safe in EP with GBM and good ECOG PS. PFS and OS was not statistically different between PTS receiving RT 40Gy or 60Gy, although we showed a trend for longer OS with RT 60Gy; in contrast, severe toxicity was higher in PTS with RT 60Gy. OS was similar between PTS receiving RT within 6 or more weeks (7-9ws) from surgery.

Impact of metformin on survival and mTOR pathway in head and neck cancer patients: An updated analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17500-e17500
Author(s):  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Jonathan Mark ◽  
Randall Butler ◽  
Joshua NeCamp ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cox Model ◽  
Progression Free Survival ◽  
Tissue Microarrays ◽  
Mtor Pathway ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Phosphoinositide 3 Kinase ◽  
Pathway Inhibition

e17500 Background: Metformin is hypothesized to suppress tumor cell growth by mTOR pathway inhibition, which mediates the phosphoinositide 3-kinase/Akt signaling pathway (frequently deregulated in human cancers). This effect is mediated by activation of the AMP protein kinase (AMPK). Despite knowledge of the mechanism, various retrospective studies show conflicting results about effect of metformin on survival in head and neck squamous cell carcinoma (HNSCC) patients (pts). Methods: We analyzed a retrospective cohort of 1500 consecutive pts (between 2009-2015) with HNSCC. We added about 1000 pts to previously presented data (e17514-ASCO 2016). These pts included those with diabetes (DM) on metformin (MET) or other anti-diabetic agents. Descriptive statistics were used for demographic and pt data. Kaplan-Meier method was used to calculate median overall survival (OS) and progression free survival (PFS), 95% CI. Cox model was used to test association between MET (or DM) and OS (or PFS) (using SPSS-24 (IBM)). Results: Of the 1500 pts with HNSCC, 329 had advanced cancer (stage III/ IV), and received definitive chemo-radiation (CRT). Of these, majority were Caucasian (90%), males (90%) and smokers (70%). Mean age at diagnosis was 57 years (SD 10). 53 pts had DM, of which 37 were on MET. Statistical results are shown in Table 1. Conclusions: This retrospective study showed no statistically significant difference between various subgroups described in the table. Given the low number of diabetics, and pts on MET, data is limiting. However, further subset analyses are ongoing to determine whether a difference in treatment (RT vs. cetuximab vs. cisplatin) had an impact on outcomes. Future experiments will utilize tissue microarrays to evaluate for association with mTOR pathway aberrations. [Table: see text][Table: see text]

Initial reporting of NRG-LU001 (NCT02186847), randomized phase II trial of concurrent chemoradiotherapy (CRT) +/- metformin in locally advanced Non-Small Cell Lung Cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8502-8502 ◽  
Author(s):  
Theodoros Tsakiridis ◽  
Chen Hu ◽  
Heath Devin Skinner ◽  
Rafael Santana-Davila ◽  
Bo Lu ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Clinical Models ◽  
Nsclc Patients ◽  
Clinical Trial Information

8502 Background: Metformin, a diabetes agent that inhibits mitochondria complex I, enhances radiotherapy and chemotherapy responses in pre-clinical models of NSCLC. NRG-LU001 examined whether metformin can improve outcomes of curative CRT in locally advanced (LA)-NSCLC. Methods: The primary endpoint of this trial was 1-year progression free survival (PFS). Unresected, non-diabetic, stage IIIA/B NSCLC patients were randomized (1:1) to either carboplatin-paclitaxel chemotherapy concurrent with chest RT (60Gy), followed by consolidation carboplatin-paclitaxel chemotherapy (Control Arm) or the same and oral metformin (2000mg daily) during cytotoxic therapy (Experimental Arm). PFS and overall survival (OS) were estimated with the Kaplan-Meier method; time to local-regional progression (TTLRP), time to distant metastasis (TTDM) were estimated using the cumulative incidence method. Adverse events (AEs) were graded with CTCAE v.4.0. Results: Between Aug.2014 and Dec.2016, 170 patients were accrued. Analysis was planned at 102 PFS events (Feb. 2019). There was no significant difference in rates or grade of toxicity between the two arms. 1- and 2-year PFS was 60.4% (95% CI: 48.5, 70.4) and 40.1% (95% CI: 29.0, 51.0) in Control vs 51.3% (95% CI: 39.8, 61.7) and 34.5% (95% CI: 24.2, 45.1) in the Metformin arm (multivariable Cox proportional HR=1.20 (95% CI: 0.81, 1.78), p=0.36). OS at 2 years was 65.4% (95% CI: 53.5, 75.0) for Control vs 64.9% (95% CI: 53.1, 74.5) for the Metformin arm (HR=1.03 (95% CI: 0.64, 1.68)), while deaths due to disease were 90% vs 71%, respectively. No significant differences were found for TTLRP or TTDM. Conclusions: NRG-LU001 center reported outcomes show that oral daily metformin was well-tolerated in combination with CRT treatment for LA-NSCLC. However, metformin did not improve PFS and OS and did not alter the rates of local-regional failure or distant metastasis. Acknowledgements: TT and HS are Co-Principal Investigators. This project was supported by National Cancer Institute (NCI) grants: U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG SDMC), UG1CA189867 (NCORP), U24CA180803 (IROC). Clinical trial information: NCT02186847.

Doxil, Vincritine, Reduced Frequency Dexamethasone in Combination with Thalidomide (DVd-T) Is Associated with Higher Overall and Progression Free Survival as Compared to DVd in Patients with Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2557-2557 ◽  
Author(s):  
Khaldoun Almhanna ◽  
Revathi Suppiah ◽  
Rachid Baz ◽  
Mary Ann Karam ◽  
Beth Faiman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow Involvement ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Disease Stage ◽  
P Value ◽  
Free Survival ◽  
Number Of Patients

Abstract Background: Although initially responsive to chemotherapy, multiple myeloma ultimately relapses. Replacing Adriamycin with pegylated liposomal doxorubicin in the VAD regimen results in a regimen with better safety profile (less neutropenia, alopecia, fewer hospital and clinic visit). DVd resulted in normalizing the angiogenic process however this did not improve PFS or OS. Thalidomide because of its antiangiogenic, immunomodulatory effects and chemo-sensitizing activity through modulating integrins was added to the DVd regimen. Adding the thalidomide to the DVd regimen resulted in an overall response rate of 89% with a CR/NCR rate of 49 % as compared to 60% and 18 % respectively for the DVd. At this stage it is not clear if the quality of response affects outcome in multiple myeloma patients receiving conventional dose therapy. To better assess the prognostic implication of improved quality responses and to define the role of up front Thalidomide, we compared the DVd to the DVd-T regimen by retrospectively reviewing the two trial data, the follow up for both trials is mature. It is still not clear whether thalidomide is more appropriately used up front or in the management of relapse. Methods: we recruited a total of 68 patients in our DVd trial versus 105 patient in the DVd-T trial. A total of 155 patients in both groups were evaluable for follow-up and response (58 received DVd and 97 received DVd-T). Patients were matched for age, disease prognosticators, disease stage, and bone marrow involvement. The newly diagnosed patients were comparable in both groups except for the b 2 microglobulin which was higher in the DVd-T group as compared to the DVd (3.2 vs. 5.0; respectively. p0.05). In the relapsed/refractory group of patients, all variables were comparable. Results: The median follow up was 5 years for the DVd group and 2 years for the DVd-T group. Median age for the DVd was 62 years, which was similar to the DVd-T. For the DVd vs. the DVd-T group of patients achieving complete and near complete remission was 17% vs. 49.5% respectively with a p value of 0.001. Progression free survival was significantly longer for the DVd-T regimens vs. the DVd (28 vs. 13 months p= 0.0002) Figure 1., and for over all survival the median is not reached for the DVd-T vs. 28 months for he DVd (p=0.006). Conclusion: we conclude that the addition of thalidomide significantly improved the quality of response and this appears to translate in to a PFS and OS benefit. While, recently published SWOG data suggests that the overall survival is determined by the duration of the PFS and not the quality of the response, this discrepancy could be related to the small number of patients in our study or the lack of use of biologic immune modulators among SWOG patients. Figure Figure

Continuous Administration of Low-Dose Cyclophosphamide and Prednisone as a Salvage Treatment for Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4962-4962
Author(s):  
Fan Zhou ◽  
Lieping Guo ◽  
Haotian Shi ◽  
Chenhui Lin ◽  
Jian Hou
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Salvage Therapy ◽  
Low Dose ◽  
Severe Infection ◽  
Progression Free Survival ◽  
Comorbid Conditions ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Median Progression Free Survival

Abstract Abstract 4962 Objective To assess the efficacy and tolerability of continuous low-dose cyclophosphamide and prednisone regimen (CP) as a salvage therapy for multiple myeloma (MM). Method The CP regimen consisted of oral cyclophosphamide at 50 mg and prednisone at 15 mg daily. A total of 27 consecutive patients received the CP regimen: 19 patients had severe comorbid conditions; 8 were unwilling to continue conventional chemotherapy due to severe infection associated with conventional treatment. All patients had received 1-4 chemotherapeutic regimens prior to the current study. Result The overall response rate (complete remission, very good partial response, and partial response) was 66.7%. The median time to response was 2 months. In the patients who responded to the treatment, the median progression-free survival has not been reached. In the non-responding patients, the median progression-free survival was 4 months. In patients with severe comorbid conditions and unwilling to accept conventional chemotherapy because of severe infection, the physical conditions improved significantly. Conclusion Continuous low-dose CP regimen is an effective and well-tolerated salvage therapy for MM. Disclosures No relevant conflicts of interest to declare.

Bortezomib-Based Regimens As Consolidation Therapy after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Single Center Experience from Oran (Algeria)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5121-5121 ◽  
Author(s):  
Souad Talhi ◽  
Soufi Osmani ◽  
Mohamed Brahimi ◽  
Kamila Amani ◽  
Hafida Ouldjeriouat ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Significant Difference

Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma (MM) patients and is associated witha significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, the majority ofpatientsrelapse. This study compares the efficacy of autologous hematopoietic stem cells followed by consolidation bybortezomibbased regimens to the no consolidation therapy in adult patients. PATIENTS AND METHODS: This is a retrospective study over a period of 7 years (2009-2015). All patients less than 65 years with a newly MM diagnosis were included. The protocol used in induction was VD (n=47) treatment whichconsisted of four 3-week cycles of 1.3 mg/m2 bortezomib administered subcutaneously (SC) on days 1, 4, 8, and 11 and 40 mg dexamethasone on days 1Ð4 and 9Ð12. Therapy with VTD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 100 mg/day thalidomide administered orally. Therapy with VCD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 500 mg/m2 cyclophosphamide administered orally on days 1, 8, and 15. Recommended concomitant medications included bisphosphonates, antibiotics, and antiviral prophylaxis. Acetyl salicylic acid was systematically used in the VTD arm. Stem cells were mobilized with 15 or 10 microg/kg G-CSF alone. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4¡C until reinfusion on day 0. The target yield was 2 x106 CD34+ cells/kg. Following induction therapy, all patients had to proceed to ASCT. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients.The consolidation regimen consisted of two cycles of VD or VCD or VTD after autologous stem- cell transplantation. In our study patients were divided into two groups: Group1 (ASCT plus consolidation) and Group 2 (ASCT alone). The therapeutic evaluation focused on the overall response (CR + VGPR) and progression free survival (PFS) and overall survival (OS) calculated by the Kaplan-Meier method. RESULTS: Over a period of 7 years, 153 patients were collected divided in two group: G1 (n=71) and G2 (n=82). Baseline characteristics are summarized in Table 1. No significant difference was observed between the 2 groups. In terms of CR, 58% of the patients in the G1 achieved a CR after consolidation vs 33% in the G2 after ASCT alone (p=0.007). In terms of VGPR, 31% of the patients in the G1 achieved a least a VGPR vs 17% in the G2 (p=0.04). The relapse rate was significantly lower in the G1 (10%) than the G2 (39%), (p=0.0001). The median follow-up period was 23,4 months. PFS was significantly higher in the G1, median no reached vs 37 months in the G2 (p=0.02) but no significant difference was observed in terms of OS rate between the 2 groups, 91% (G1) versus 82% (G2) at 27 months (p=0.7). CONCLUSION: We conclude thatbortezomib-based regimens as consolidation therapy after ASCT in patients with MM was effective in the improvement of PFS and response rate. Table Patients characteristics. Table. Patients characteristics. Disclosures No relevant conflicts of interest to declare.

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