First-line CyborD treatment for graft ineligible multiple myeloma patients: Real-life efficacy and tolerability.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20516-e20516
Author(s):  
Dominic Duquette ◽  
Marie-Michelle Germain

e20516 Background: CyborD is a regimen that was widely adopted in Canada around 2010 despite very little data supporting it’s use. The aim of the study is to describe the efficacy and tolerability of First line CyborD regimen for graft ineligible myeloma patients. Methods: This is a retrospective study at two centres in the CHU de Québec for patients with graft ineligible multiple myeloma patients treated with first line CyborD regimen between 2013 and 2018. The objectives are to describe the efficacy and tolerability of CyborD and to document PFS and OS. Results: 51 patients were included in this study with a median follow-up of 31 months. Partial response or better (≥ PR) was obtain in 84% of patients and 63% of patients achieved a very good response or better (≥ VGPR). A high rate of 26% of complete response (CR) was also obtained. A median PFS of 30 months was obtained while 75% of patients were still alive at that time. Estimated survival at 48 months was 63%. Severe toxicities (grade 3 or 4) were seen as anemia (20%), neutropenia (10%), bacterial infection (16%), diarrhea (12%) and renal toxicity (4%). Side effects related to dexamethasone in this fragile patient population reached 69% of patients but only 28% needed a dose reduction. Conclusions: First-line CyborD treatment was highly effective for graft ineligible multiple myeloma patients and this is a very well tolerated regimen. It compares favorably to RD regimen making it still an excellent first-line treatment for this elderly population. [Table: see text]

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5380-5380
Author(s):  
Salvatore Palmieri ◽  
Angela Gravetti ◽  
Stefano Rocco ◽  
Antonella Carbone ◽  
Carolina Copia ◽  
...  

Abstract BACKGROUND. In recent years, new classes of drugs have been introduced for the treatment of Multiple myeloma (MM). Several randomized trials have investigated, in the setting of first line treatment of patients eligible for autologous transplant (ASCT), the efficacy of the combination of two to four new and old drugs given as induction. Among these, VTD combination (bortezomib plus thalidomide plus dexamethasone) provided impressive results, so that it is now considered at different Institutions the standard of care as pretransplant therapy. However, data of VTD derive from clinical trials and should be verified in the "real life" setting, in terms of either efficacy or toxicity. AIMS. Here we present our experience in 76 MM patients treated between 2008 and 2014 with VTD as part of a first line treatment including also mobilization, single or double ASCT, and consolidation with two additional VD courses. No patient had been enrolled into a clinical trial. CHARACTERISTICS OF PATIENTS/METHODS. There were 39 males and 37 females, with a median age of 57 years (range 38-67). MM subtype was IgG=44 cases, IgA=15, IgD=1, micromolecular=13, non secreting=2, and solitary plasmocytoma=1. Stage according to Durie & Salmon was II-A=29, II-B=2, III-A=34 and III-B=10. In 8 cases single or multiple vertebroplasty was also necessary, while 7 patients had concomitant extramedullary plasmocytoma. In absence of CRAB criteria, patients were treated when progressive increase of M-component was observed. Treatment was given according to GIMEMA-MM-BO2005 protocol (Cavo et al, Lancet 2010) except for the following: from September 2012, bortezomib was given subcutaneously (in a total of 37 patients) and 4 instead of 3 induction cycles were given; mobilization therapy consisted of vinorelbine 30mg/sqm day 1 plus cyclophosphamyde 1500 mg/sqm day 2 (for further details, Annunziata et al, Ann Hematol 2006); consolidation did not include thalidomide and was given only from 2011; no maintenance therapy with dexamethasone was administered. RESULTS. Overall response rate after induction was 92% (70/76 patients), with 35 complete remission (CR), 25 very good partial remission (VGPR), 9 partial remission (PR) and one minimal response (MR). One patient was considered as stable disease and continued with the therapeutic program, 3 patients were refractory and were switched to salvage therapy, and 2 patients died during induction (due to fatal sepsis from H1N1 virus infection and multiorgan failure in a severely ill subject, respectively). After successful mobilization in 70/71 patients, single (n=34) or double (n=36) ASCT were given, depending on quantity of CD34+ cell collection, toxicity of first ASCT and response achieved. High dose melphalan was the conditioning regimen in all cases. After ASCT, response was upgraded in 24 cases (in 17 cases VGPR to CR, 4 PR to VGPR, 2 PR to CR, 1 MR to PR). Consolidation was given in all 47 programmed cases. Hematologic toxicity of VTD was negligible. Reduction of thalidomide schedule was necessary in 60 patients, while only 16 patients (21%) were able to complete the programmed days of therapy at 200 mg/day. In the remaining cases, 39 completed the therapy at 100 mg, 2 at 50 mg, while 19 had to definitely discontinue therapy after a median of 33 days (15-68). More frequent reasons of discontinuation or reduction were neuropathy, constipation, fatigue and skin rash; only 1 case of thrombosis was recorded in a non responding patient. Reduction of bortezomib dose was necessary only in 5 patients (all ev cases), all because of neuropathy. At the time of writing 57/76 patients (75%) are alive, with a median follow up of 27 months. The median duration of response was 38 months, 25/70 patients (36%) having progressed or relapsed. Depending on time to relapse (> or < 18 months), bortezomib or lenalidomide based salvage therapy was used. Overall and progression free survival (OS and PFS) are shown in figure 1. DISCUSSION. Our data demonstrate that the VTD combination in the real life is an extremely effective regimen in terms of response rate. Most patients after VTD are able to mobilize CD34+ cells as well as to receive ASCT. In a considerable proportion of cases reduction of thalidomide dose is required and in 25% of cases the drug needed to be discontinued. As compared to data from clinical trials, PFS in our series seems to be shorter, however our patients were unselected and in this series follow up is significantly longer. Disclosures No relevant conflicts of interest to declare.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15642-e15642
Author(s):  
R. Lin ◽  
Q. Chen ◽  
N. Fan ◽  
Y. Ye ◽  
Z. Guo ◽  
...  

e15642 Background: Primary results of POF as 1st and 2nd line treatment for AGC have been presented at ASCO 2007 and 2008. We report here data on the feasibility and the toxicity of POF versus IF(Dank, et al, ASCO 2005) in 1st line treatment of AGC. Methods: Patients with previously untreated, advanced, unresectable, and histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction were randomly assigned to POF or IF regiment. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: 25 patients were entered in this study between March 2007 and July 2007: 13 in the POF group and 12 in the IF group. The median patient age was 55 years (range, 36 to 67 years), 18 were males and 7 were females. No complete response was observed. The response rate was 62.5% (POF) and 33.3% (IF) respectively. At a median follow-up of 285 days, 7(POF) versus 6(IF) patients were still alive. Hematological toxicity was the most frequent toxicity in both groups. Grade 3 to 4 neutropenia were 38.5% (POF) versus 8.3% (IF). Diarrhea was found 0% and 8.3% in POF and IF group respectively. No grade 3 peripheral neurotoxicity was observed. Conclusions: Compared with IF regiment, POF could also be used as first-line treatment for AGC with acceptable safety profile, good efficacy, and more encouraging results. No significant financial relationships to disclose.


2017 ◽  
Vol 53 (3) ◽  
pp. 139-146
Author(s):  
Urszula Rychlik ◽  
Ewa Wójcik ◽  
Jadwiga Tarapacz ◽  
Katarzyna Brandys ◽  
Zofia Stasik ◽  
...  

Introduction: The aim of the study was to assess the prognostic value of indicators calculated on the basis of initial hematology test results of neutrophil, lymphocyte, monocyte and platelet counts (NLR – neutrophil-to-lymphocyte ratio, LMR – lymphocyte-to-monocyte ratio, PLR – platelet-to-lymphocyte ratio) in patients with ovarian cancer and their compliance with the overall response to treatment. Materials and methods: Hematological tests were performed before first course of first-line chemotherapy in 145 patients with ovarian cancer. Response to treatment was assessed according to the RECIST1.1 criteria in all patients. Results: After the completion of first-line treatment, 70 (48.3%) patients had a complete response (CR) to the therapy. In this group, progression of disease occurred in 22 (31.4%) patients during 12 months of follow-up. In the CR group with progression, 17 (77.2%) presented high NLR and PLR levels. Among 48 (68.6%) patients with CR without progression after 12 months of follow-up, high levels of NLR and PLR were observed in 21 (43.8%) and 17 (35.4%) of them, respectively. Low LMRs were observed in 16 (72.7%) patients with progression and 16 (33.3%) without progression. Conclusion: High levels of NLR and PLR and low levels of LMR before treatment seems to predict 12-month disease progression in patients with complete response to first-line treatment.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2367-2367
Author(s):  
Yating Yeh ◽  
James Chambers ◽  
Sabine Gaugris ◽  
Jeroen Jansen

Abstract Melphalan-prednisone (MP) combination has been considered a standard of care for front line treatment of multiple myeloma in patients non eligible for transplant. Melphalan-prednisone-bortezomib (MPV) combination has been approved in the United States in patients non eligible for high-dose chemotherapy (HD-C) and has recently received a positive opinion from the CHMP in Europe. Melphalan-prednisone-thalidomide (MPT) was approved in Europe in patients &gt;65 or not eligible for HD-C. There is no head-to-head trial directly comparing MPV to MPT. The objective of the current study was to compare the efficacy of MPV to MP and MPT as first line treatment of multiple myeloma in patients non eligible for transplant. Six randomized placebo controlled trials investigating the efficacy of MPT (5) and MPV (1) relative to MP were identified with a systematic literature review. The endpoints of interest were overall survival (OS), progression free survival (PFS) and overall and complete response. Relative efficacy estimates of MPT versus MP as obtained from the MPT-MP trials were combined with meta-analysis techniques and simultaneously indirectly compared with the relative efficacy of MPV versus MP from the MPV-MP trial (VISTA). This adjusted indirect comparison was performed with Bayesian fixed and random effects models. As compared to frequentist approach, Bayesian meta-analysis offers a more informative summary of the likely value of efficacy after observing the data and allows for direct probabilistic inferences. Of the three interventions compared, there was an 81% probability that MPV was the most efficacious intervention in terms of overall response and a &gt;99% probability in terms of complete response. With MPV a patient was two times more likely to show a complete response than with MPT (Relative Risk=2.15; 95%Credible Interval (CrI): 0.99–4.45). Both MPV and MPT showed greater OS than MP (HR=0.61; 95%CrI: 0.42–0.88 and HR=0.61; 95%CrI: 0.47–0.78 respectively); the indirect comparison showed similar efficacy in terms of OS between MPV and MPT (MPV vs MPT: Hazard Ratio=1.00; 95%CrI 0.64–1.57). Both MPV and MPT also displayed greater PFS than MP (MPV versus MP: HR=0.61; 95%CrI 0.49–0.76 and MPT versus MP HR=0.51; 95%CrI 0.41–0.63 respectively) and showed similar efficacy (MPV vs MPT: HR=1.19; 95%CrI: 0.87–1.63). In this study, both MPV and MPT are more efficacious than MP in terms of response, PFS and OS. MPV is expected to result in a greater complete and overall response than MPT. No difference in OS or PFS was displayed. Further analyses will need to be undertaken once evidence base data is more mature.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5745-5745
Author(s):  
Anil Vaikunth Kamat ◽  
Tariq Shafi ◽  
Raphael A. Ezekwesili

Abstract Bortezomib is a targeted proteosome inhibitor licensed & approved for in multiple myeloma both as first line and in relapsed setting. This is a retrospective non experimental cross sectional quantitative comparative group study using clinical case notes, laboratory & pharmacy records for patients treated with Bortezomib in 2011 & 2012. Outcomes studied included remission status, adverse events, progression free survival and overall survival at follow up. The study also looked at the comparative responses of cohort of patients administered Bortezomib through intravenous & subcutaneous route. The cohort consisted of 33 patients, 21 male, 11 female, median age 71 years, first line 10 patients, second line 23 , median number of cycles in 2011 & 2012 – first line 3 & 8 , second line 5 & 4, respectively. In 2011, 8 received intravenous treatment, 9 were switched from intravenous to subcutaneous route whilst all patients from 2012 received subcutaneous Bortezomib. The most frequently used regimen was Bortezomib Dexamethasone ( VD). The overall response rate ( ORR >/= Minor Response) was: First line 70% (7/10) ; Second line 47.8% ( 11/23); median PFS ( Figure 1) 6 months ( First line: 7 months ; Second line : 6 months) and median overall survival ( Figure 2) at follow up: 9 months ; 39.4 % ( 13/33) First line 8.5 months, Second line 11 months. Subcutaneous Bortezomib was equivalent to intravenous Bortezomib in terms of efficacy & tolerance. Of 33 patients, there were 12 dose reductions. Adverse events reported included: peripheral Neuropathy - grade 3 - 6% ( all grades 27.3%); Diarrhoea - grade 3 - 3% (all grades 6%); Nausea / Vomiting - grade 3 - 3% ( all grades 6%) and Second Primary Malignancies - 12% ( 4 of 33). Mortality at follow up was 20 patients from cohort of 33 ; causes included disease progression in 11, second primary malignancy with disease progression in 4, COPD 2, Systemic Amyloidosis 2, Tuberculosis 1 , Multiple co morbidities 1 and Asthma with mechanical failure in single patient. Second primary malignancies ( 4/33) included Prostate carcinoma ( 1), Renal Cell Carcinoma (1), Neuroendocrine tumour ( 1 ) and Unknown Primary in single patient. Beyond second line treatment, majority (14 of 23 patients; 60.9 %) did not have further active treatment. These data indicate that patient outcomes were modest compared to published data from VISTA and APEX trials. Majority of patients did not have further active treatment beyond second line which suggests the most effective treatment strategy should be used upfront as patients may not be fit to have further lines of therapy despite availability of recently introduced novel targeted agents. A higher percentage of second primary malignancies were noticed in this cohort which should be an area of further clinical research. Figure 1: Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 1:. Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 2: Overall survival with Bortezomib as first line & second line in multiple myeloma Figure 2:. Overall survival with Bortezomib as first line & second line in multiple myeloma Disclosures No relevant conflicts of interest to declare.


2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4894-4894
Author(s):  
Tereza Popkova ◽  
Ludek Pour ◽  
Ivan Spicka ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
...  

Abstract Introduction: Although highly effective agents and novel therapeutic strategies are being developed, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has not been overcome in the first-line treatment for fit patients (pts) with multiple myeloma. The objective of this work is to retrospectively analyze the use of this procedure in newly diagnosed Czech patients. Methods: Data were derived using the Czech Myeloma Group Registry of Monoclonal Gammopathies. By February 2 nd 2021, a total of 2154 newly diagnosed multiple myeloma patients who underwent HDT/ASCT were identified. Results: At the time of multiple myeloma diagnosis, the median age was 59 years; 24%/56%/14%/5%/1% pts were ECOG 0/1/2/3/4; 44%/32%/24% pts were ISS stage I/II/III; 14.5%/17.5%/68% and 84%/16% pts were Durie-Salmon stage I/II/III and subclassification A/B, respectively. The combinations of agents used in the induction regimen were proteasome inhibitor (PI), immunomodulatory drug (IMiD) and glucocorticoid (GC) in 28.5% (613/2154) pts; PI, GC and chemotherapy (CHT) in 24.8% (534/2154) pts; GC and CHT in 22,5% and IMiD, GC and CHT in 16.1% (346/2154). Other combination of drugs was used in 8.2% (177/2154) pts. It was registered that 3.7% (79/2154) induction regimens were switched to a different combination because of toxicity, patient's choice, poor peripheral venous access or other reasons. Single HDT/ASCT was performed in 77.3% (1665/2154) cases whereas tandem HDT/ASCT was given to 11.8% (254/2154) patients. In 10% (215/2154) cases, the transplantation technique was not specified. Nine percent (193/2154) patients were treated within a clinical study. The median progression free survival (mPFS) and the median overall survival (mOS) of the whole cohort was 28.9 and 92.1 months, respectively. Information about response to treatment before and after the high-dose therapy were available for 75.7% (1627/2154) and 92.2% (1987/2154) patients, respectively. Disease status at the time of HDT/ASCT was defined as stringent complete response (sCR) at 2.2% (36/1627), complete response (CR) at 11.9% (194/1627), very good partial response (VGPR) at 38.2% (621/1627), partial response (PR) at 40.9% (666/1627), minimal response (MR) at 3.6%, (58/1627), stable disease (SD) at 2.2% (36/1627), progressive disease (PD) at 1% (16/1627) patients. The overall response rate (ORR) on day 100 was 92.8% (sCR: 10.5% [209/1987], CR: 22.4% [446/1987], VGPR: 35% [696/1987], PR: 24.8% [493/1987], MR: 2.7% [54/1987], SD: 1.4% [27/1987], PD: 3.1% [62/1987]). We also performed a survival analysis of patients progressing up to 18 months after HDT/ASCT (n=1219) versus patients progressing in more than 18 months (n=935). The median OS was 41.5 versus 124.9 months, respectively. An analysis of the role of tandem HDT/ASCT in this real-world cohort will be presented at the conference. Conclusion: Globally as well as in the Czech Republic, HDT/ASCT is an important therapeutic approach in the first-line treatment of multiple myeloma. Our analysis of 2154 newly diagnosed transplant-eligible patients confirms high effectiveness - ORR of 92.8%, mPFS of 28.9 months, and long-term survival reaching mOS of 92.1 months. Disclosures Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
R. E. Lamar ◽  
D. R. Spigel ◽  
H. A. Burris ◽  
T. M. Markus ◽  
M. Kuzur ◽  
...  

2018 Background: Anti-angiogenesis agents have recently shown activity in the treatment of patients (pts) with GBM. We added sorafenib, a multi-targeted TKI, to the standard first-line treatment of patients with GBM. Methods: Pts with histologically documented GBM were eligible at diagnosis or after resection. Additional entry criteria: ECOG PS 0 or 1; adequate organ function; ability to swallow pills; standard exclusions for antiangiogenesis agents. All pts initially received radiation therapy (total 60 Gy, 2 Gy by single daily fractions) plus temozolomide (75mg/m2 po daily). Four weeks after completion of radiation therapy, pts received temozolomide (150mg/m2 po days 1–5, repeated every 21 days for 6 cycles) plus sorafenib (400mg po bid daily x 24 weeks). Pts were evaluated every 8 weeks during temozolomide/sorafenib therapy, and every 3 months after therapy ended, until tumor progression. Median PFS was the primary endpoint. Results: Between April 2007 and July 2008, 45 pts were enrolled. The median age was 54 years; 30 pts (67%) had previous partial or complete surgical resection. 39 pts (87%) completed concurrent RT/temozolomide therapy, while 6 pts were removed from treatment (PD 4, toxicity 1, intercurrent event 1). 39 pts began treatment with temozolomide/sorafenib; 3 have completed all planned treatment, 8 remain on treatment, and 28 stopped treatment early (PD 22, toxicity 2, intercurrent event 1, pt decision 3). Best responses are as follows: CR, 1 pt (2%); PR, 5 pts (11%); stable disease, 22 pts (49%); progressive disease, 14 pts (31%). After a median follow-up of 9 months, median PFS for all pts was 6 months (95% confidence intervals, 2.7–7.8 months). Median PFS for pts who received at least 1 dose of sorafenib is also 6 months. The median overall survival is 16 months (95% CI, 7.2-NR months). Grade 3/4 toxicity during temozolomide/sorafenib was uncommon; 7 pts (16%) required dose reductions of sorafenib during their treatment course. Conclusions: The addition of sorafenib to standard treatment with RT/temozolomide is feasible and well tolerated by most pts. Preliminary efficacy is similar to standard therapy; updated results will be presented. [Table: see text]


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3987-3987
Author(s):  
Carlos Fernández de Larrea ◽  
Raquel Jiménez ◽  
Laura Rosiñol ◽  
Eva Giné ◽  
Natalia Tovar ◽  
...  

Abstract Abstract 3987 Background: Autologous stem cell transplantation (ASCT) is the gold standard as first-line treatment in young patients with multiple myeloma (MM). Prognostic factors have been usually related to patient characteristic and disease stage. Few investigations on the pattern of relapse or progression after ASCT have been addressed. The differentiation of serological or asymptomatic progression versus clinical relapse requiring treatment is also an important issue. The aim of this study was to investigate the characteristics at the time of relapse or progression in patients with MM who received ASCT as part of a first-line treatment. Patients and Methods: Two-hundred and eleven patients underwent melphalan-based ASCT at our institution during the last 18 years. Of these, 170 patients (87M/83F; median age 56 years, range 25 to 70) who achieved at the least a minimal response (PR) after no more of two induction lines before ASCT are the basis of this study. Initial baseline demographics, clinical and laboratory data at relapse or progression, and information concerning treatment and follow up were collected. The M-protein heavy-chain isotype was IgG (57%), IgA (23%), light chain only (14%) and others (3.5%). Only 2.5% were oligosecretory MM. Extramedullary plasmacytomas (EMP) were observed in 37 out of 170 patients (22%) at diagnosis. The ISS stage was I (45.3%), II (26.5%), III (18.8%) and unknown (9.5%). 12.6% of the patients had a serum creatinine level ≥2 mg/dL and 16.2% had hypercalcemia. The median follow-up for alive patients was 3.9 years (range 4 months to 18 years). Response, relapse, and progression were defined according to European Blood and Marrow Transplantation (EBMT) criteria. Results: Median PFS was 3.3 years (CI 95% 2.7 to 3.9 years) and the median OS of 6.8 years (CI 95% 3.9 to 9.6 years). 47.7% of the patients achieved a complete remission (CR). As of December 2011, 93 patients (54.7%) had relapsed or progressed after ASCT. 37 out of the 93 patients (40%) had relapsed from CR, while the remaining 60% had progressed from PR. A serological or asymptomatic relapse/progression was as frequent as a symptomatic one (49.5% vs. 50.5%, respectively), the latter requiring immediate treatment in the median of a month. Patients with serological relapse/progression had a significantly longer OS than those requiring immediate treatment (p=0.002)(Figure). The main clinical reasons to start myeloma therapy were anemia (43%), new bone lytic lesions (36%), EMP (23.7%), bone pain (14.4%), renal insufficiency (12.2%) and/or hypercalcemia (9%). 22 of the 93 patients (24%) relapsed/progressing patients had EMP at the time of progression. In three of them, the extramedullary involvement was the only criteria of progression. The presence of EMP at diagnosis was significantly associated with extramedullary disease at relapse (p=0.001). In fact, 12 out of the 22 patients (54.5%) with EMP at relapse had also EMP at the time of diagnosis. Median time between serological relapse or progression and treatment was of only 5.6 months (range 0 to 5.6 years). However, in 12 out of 46 patients (26%) with serological relapse/progression, treatment was not initiated within first two years. Finally, time to next treatment was significantly longer in patients relapsing from CR (median 2.85 years; CI 95% 2.1 to 3.6) vs. those progressing from PR (median 1.65 years; CI 95% 1.1 to 2.2) (p=0.017). Conclusion: After ASCT, serological or asymptomatic relapse/progression is observed in about one half of the patients. The treatment-free interval in these patients is longer in patients relapsing from CR than in those progressing from PR. Patients with symptomatic relapse/progression have shorter OS. Extramedullary involvement is frequent, being the highest risk in patients with EMP at diagnosis. Finally, relapse/progression with extramedullary disease only is rare. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5354-5354
Author(s):  
Marcio M Andrade Sr. ◽  
Ilda Murillo-Florez ◽  
Anel Montes-Limon ◽  
Beatriz de Rueda ◽  
Jose-Maria Grasa ◽  
...  

Abstract Background Proteasoma inhibitors have proven to be one of the major advances on multiple myeloma (MM) therapy. Their principal effect in growth inhibition of MM cells is achieved not only through the inhibition of proteasomes but also by preventing the adhesion of myeloma cells to stromal cells, induction of cytokines by the microenvironment, decrease angiogenic activity and a direct apoptotic effect on MM cells. Actually it is part of the first-line standard of care therapy for patients with MM. On the other hand, multiple strategies have been developed for trying to predict response or improve the assessment of response and follow-up of MM patients. Currently, the International Myeloma Working Group (IMWG) criteria of response include immunophenotype and immunoparesis analysis. The HevyLiteTM and FreeLiteTM assays (The Binding Site Ltd. Birminghan. UK) permit a separate quantification of the amount of kappa- and lambda-bound to a given immunoglobulin (HLC) and the free light chains kappa or lambda amount quantification (FLC), both being excellent tools for immunoparesis assessment. Aims To analyze the usefulness of immunoparesis analysis by HevyLiteTM and FreeliteTM in patients who receive bortezomib-based therapy in our institution. Patients and Methods A retrospective chart review was performed including the patients diagnosed with secretor IgA or IgG MM who received therapy with bortezomib either at relapse or as first-line therapy. General clinical characteristics, therapy schedules, number of cycles, response to therapy according IMWG criteria and relapse were recorded. For the analysis, only patients with at least 4 cycles of bortezomib based regimen and HLC and/or FLC analysis performed between 4-12 weeks after complete therapy were included. Period of study: June 2004 to April 2013. Results At the end of study a total of 67 MM patients had received bortezomib-based therapy, 63 of them completed 4 or more cycles and were included in the analysis. Male/Female ratio: 31/32, mean age: 66.9 years old (46-81), therapeutic schedules were: bortezomib-prednisone: 3 (4.7%), bortezomib-dexametasone: 33 (51.6%), bortezomib-melfalan-prednisone: 18 (28.1%), bortezomib-dexametasone-lenalidomide: 8 (12.5%) and bortezomib-talidomide-dexametasone: 1 (1.6%). 55% of patients received at least 6 cycles of therapy. Immunoglobulin Myeloma subtype: IgAL: 13 (20.4%) patients, IgAK: 10 (15.6%) patients, IgGK: 32 (50.8%) patients and IgGL: 8 (14.1%) patients. A total of 46 (73%) patients showed an abnormal HLC ratio at diagnosis and 48 (76,2%) had immunoparesis before therapy; a total of 47 (74.6%) registered an abnormal FLC ratio at diagnosis. The response to therapy was: 15 (23.8%) of cases achieved a stringent complete response (SR), 3 (4.8%) a very good partial response (VGPR), 36 (57.1%) obtained a partial response (PR) and 9 (14.3%) patients had not-response/progressive-disease. At the time of post-therapy evaluation, 26 (37%) of patients had normalized FLC-ratio, 15 (23.8%) maintain the SR, 1 (1,6%) patient in VGPR and 5 (11.1%) in PR and 1 (1.6%) of non-responder patients. Normalization of HLC-ratio was only observed in patients with SR and VGPR: 13 (20.6%). Regarding the immunoparesis analysis, only 15 (23.8%) of patients with immunoparesis recovered the immune restitution (IR) at the end of therapy, of which 8 (11.7%) were SR patients, 2 VGPR and 5 PR patients. At the end of the study 47(71.4%) patients relapsed, 5 (11.11%) are on maintenance therapy and 11(17.4%) after a median follow-up of 29 months (9-94) without therapy not-relapsed; the association of SR with IR was related to a less tendency to relapse and need of therapy, 7/8 patients who achieved this status are not-relapsed. Conclusion In our cohort, patients who achieved a SR with a normalization of immunoparesis shows a clear tendency to less incidence of relapse; probably reflecting a better response with not only an undetectable monoclonal protein but also the recovery of the immune function. Even in small cohorts, the immunoparesis recovery analysis through HLC quantifications seems to be an useful tool to determine a new level of response. More investigations on this field are warranted. This work has been partially supported by a grant from Fundación para el Estudio de la Hematología y hemoterapia en Aragón (FEHHA) Disclosures: No relevant conflicts of interest to declare.


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