scholarly journals Study of prognostic factors in multiple myeloma

2021 ◽  
Vol 8 (11) ◽  
pp. 1694
Author(s):  
Geeta Rathnakumar ◽  
Kinjalka Ghosh ◽  
Nikhil Choudhary ◽  
Narendra Kamble ◽  
Nitin Inamdar

Background: Multiple myeloma (MM) is cancer of the plasma cell characterized by interpatient heterogeneity, in most of the cases it is incurable. It is the second most common hematological malignancy. Overall survival of patients has significantly increased recently. Lot of research is going on for prognostic factors, which can predict disease and response to therapy. During the past decades, biomarkers: M protein and β2 microglobulin have shaped the knowledge about MM. This study was undertaken to evaluate the role of prognostic factors in newly diagnosed and few follow up patients of MM before, during and after the treatment in Indian population.Methods: We analyzed 177 samples (90 MM patients and 87 healthy control) for creatinine, calcium, phosphorus, LDH, total protein, albumin, globulin, β2M, Immunoglobulines (Igs), IgG, IgA, IgM, Kappa light chain and Lambda light chains, serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE).Results: The result of our study are significant at p<0.0001 for creatinine, β2M, LDH, albumin, globulin and immunoglobulins whereas for calcium and phosphorus results are not significant at p<0.005. We observed that the levels of β2m, creatinine, LDH and M band concentration declined during the treatment (chemotherapy).Conclusions: We conclude that these results will help the clinicians to tailor-made the chemotherapy doses for betterment of patients and improve survival rate in MM patients.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Fredrik Borgsten ◽  
Xenia Gatopoulou ◽  
Marta Pisini ◽  
Magnus Tambour ◽  
Frida Schain ◽  
...  

Background In the last decades the introduction of novel drugs has greatly improved the prognosis of multiple myeloma (MM) patients. We have investigated healthcare resource utilization and sickness absence-associated productivity loss over time in a population-wide, retrospective registry study in Sweden. Methods 8,693 patients were identified in the National Cancer Register with a MM diagnosis from July 2001 to December 2015 and followed until 2016. Specialized healthcare usage (inpatient admissions and outpatient visits) were obtained from the Patient Register and costs were estimated by weighted DRG codes. For patients under 66 years of age, sickness absence and salary information were obtained by linkage to the LISA Register. Analyses were performed separately on patients who underwent autologous stem cell transplantation (ASCT) (n=1,425) and on non-transplanted patients (n=7,012) and stratified by diagnosis periods 2001-2005, 2006-2010 and 2011-2015 to reflect increased introduction of effective drugs into clinical care. Median age was 60 years in the ASCT group and 75 years in the non-ASCT group. Results The number of MM patients that underwent ASCT increased over time (n= 282 in 2001-2006 to n= 592 in 2011-2015). MM patients diagnosed most recently had improved overall survival (OS), with five-year OS rate increasing from 52% to 58% to 62% for patients diagnosed in 2001-2005, 2006-2010 and 2011-2015, respectively (p&lt;0.0001). Patients diagnosed during 2011-2015 spent on average 20% and 9% less total time in specialized healthcare than patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at ASCT, weighted comorbidity score at ASCT and per follow-up year and education at ASCT). This decrease was driven by less usage and time in both inpatient and outpatient care. Adjusted sickness absence time decreased by 41% and 38% in the third follow-up year for patients diagnosed during 2011-2015 compared to patients diagnosed during 2001-2005 and 2006-2010, respectively. Productivity loss costs represented about 45% of total costs (healthcare resource costs ~55%) in the first two follow-up years, but decreased over time. The cumulative median per person cost (healthcare- and productivity-related) over the three follow-up years post-diagnosis decreased by 21% in 2011-2015 (€52,273) compared to 2001-2005 (€66,182), despite an 8% increase in three-year OS over the same period. The number of non-ASCT MM patients also increased over time (n=2,053 in 2001-2005 to n= 2,587 in 2011-2015). Median survival increased from 2.5 years to 3.4 years for patients diagnosed during 2001-2005 compared to 2011-2015. Average total time spent in specialized healthcare was reduced by 29% and 12% for patients diagnosed during 2011-2015, compared to patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at diagnosis, weighted CCS at diagnosis, weighted CCS per follow-up year and education at diagnosis). This was associated with decreased need for inpatient care and a shift towards more outpatient usage. By the third follow-up year, the adjusted sickness absence time in patients diagnosed during 2011-2015 was reduced by 44% and 23% compared to patients diagnosed in 2001-2005 and 2006-2010, respectively. Productivity loss accounted for approximately 15% of total costs (healthcare resource costs ~85%) and was stable over follow-up years. The cumulative median per-person cost (healthcare- and productivity-related) over three follow-up years was similar for patients diagnosed in 2001-2005 (€25,621) and 2011-2015 (€26,592), despite a 12% increase in three-year OS over the same period. Conclusion The availability of new treatment options for MM patients in Sweden over time was associated with less healthcare usage, less time spent in healthcare and lower productivity loss due to sickness absence for both ASCT and non-ASCT-treated patients. These improved clinical and economic outcomes provide policy makers, healthcare providers and physicians with invaluable real-world insights for cost-benefit considerations in the continued development and introduction of effective treatments for MM. Figure 1 Disclosures Borgsten: Janssen: Current Employment. Gatopoulou:Janssen: Current Employment. Pisini:Janssen: Current Employment. Tambour:Janssen: Current Employment, Current equity holder in publicly-traded company. Schain:Schain Research: Current Employment, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Jones:Schain Research: Current Employment. Kwok:Schain Research: Other: Internship . Hjortsberg:Janssen: Current Employment.


2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0046
Author(s):  
Carola Pilone ◽  
Federico Verdone ◽  
Roberto Rossi ◽  
Davide Bonasia ◽  
Federica Rosso

Objectives: High Tibial Osteotomy (HTO) is widely performed to treat early arthiritis in the varus knee. The aim of this prospective study is to evaluate different prognostic factors affecting the outcomes of HTO and, with special attention to the role of the site of deformity. Methods: 231 Opening Wedge HTO (OWHTO) were performed in 202 patients and included in the study. Inclusion criteria were: 1) age > 18 years, 2) no major associated procedures (i.e. ACL reconstruction, major cartilage procedure, 3) only OWHTO, 4) pre-operative complete clinical and radiological evaluation available. Patients were evaluated with (1) the Knee Society score (KSS), (2) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, (3) another self-evaluation scale, (4) long-leg radiographs, and (5) plain radiographs. On the x-ray different angles were evaluated, including Join Line Congruence Angle. Furthermore, the location of deformity was established. Three main outcomes were identified: Indication to Total Knee Arthroplasty (TKA), KSS poor or fair and WOMAC < 76 points), and different prognostic factors were identified (Fig. 1). All the variables were firstly tested in a single regression model to evaluate the association with each outcome. All the variables with p<0.1 were re-tested in a multiple regression model. Results: 32 patients were lost to follow-up and 31 patients did not meet the inclusion criteria, leaving 139 patients (156 OWHTOs) for the study. The average age was 52.9 ± 9.6 years, and the average follow-up was 97.7 ± 42.8 months. Post-operatively there was a significant improvement in both the KSS and WOMAC score compared to the pre-operative period (p<0.0001). The only variable related to TKA indication was a pre-operative JLCA ≥5° (OR=24.3, p=0.0483). Conversely, different variables were related to a worse KSS, including pre-operative BMI >30 Kg/m2 (OR=78.9, p=0.0028), pre-operative ROM <120° of flexion (OR=40.8, p=0.0421), pre-operative mLDFA ≥91° (OR=36,6,p=0.0401) and femoral pre-operative CORA ≥3° of varus (OR=39,9 p=0.0269). Furthermore, a pre-operative BMI >30 Kg/m2 (OR=29,5, p=0.0314) was associated to a worse WOMAC score. Conversely, patients with a pre-operative mMPTA ≤84° had lower risk to obtain a worse KSS oe WOMAC score (respectively OR= 0,2 p=0.0364 and OR=0,3 p=0.0071). The cumulative survivorship was calculated with the Kaplan-Meier method, and it resulted equal to 98.6% at 5 years and decreased to 85.5% at 10 years. Conclusion: OWHTO is a good treatment for early arthritis in the varus knee if the correct indications are applied. The outcomes can be considered good, with 85% of 10-year survivorship. It is mandatory to correctly address the location of the deformity, because the presence of a femoral varus deformity is related to worse outcomes. Similarly, presence of a pre-operative JLCA ≥5° is the only factor associated to TKA indication. [Table: see text]


2018 ◽  
Vol 23 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Ludmil Mitrev ◽  
Nayan Desai ◽  
Ahmed Awad ◽  
Sajjad Sabir

The past 2 decades have seen a proliferation of transcatheter mitral valve (MV) therapies, which are less invasive and distinct from surgical MV repair or replacement. The commonly used MV transcatheter therapies include (1) percutaneous mitral balloon commissurotomy (PMBC) for rheumatic mitral stenosis; (2) edge-to-edge repair with the MitraClip for mitral regurgitation; (3) valve-in-valve implantation in bioprosthetic MV, native MV, or mitral ring; and (4) closure of paravalvular leaks (PVLs). This article will focus on the use of echocardiography in the diagnosis, patient selection, procedural guidance, and postprocedural follow-up for PMBC, with notes on the role of transesophageal echocardiography in transcatheter interventions for prosthetic valve degeneration and PVL closure.


2019 ◽  
Vol 64 (3) ◽  
pp. 195-207 ◽  
Author(s):  
Yoshiaki Norimatsu ◽  
Kenji Yanoh ◽  
Yasuo Hirai ◽  
Tetsuji Kurokawa ◽  
Tadao K. Kobayashi ◽  
...  

The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping, and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to reevaluate the role of endometrial cytology. LBC samples are easier to screen compared to conventional ones, due to a smaller screening area and an excellent quality of cell preparations. LBC by using peculiar cytoarchitectural features is a useful tool in the cellular diagnosis and follow-up of abnormalities, which, however, remains complementary to histopathology and to the emerging molecular diagnostic cytopathology. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. Herein, we also summarize the process and rationale by which updates were made to the standardized terminology in 2018 and outline the contents of the new Bethesda-style classification (the Yokohama system) for the endometrial cytology.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4871-4871
Author(s):  
Roland Fenk ◽  
Mark Korthals ◽  
Guido Kobbe ◽  
Ulrich Steidl ◽  
Thorsten Graef ◽  
...  

Abstract Background: High-dose chemotherapy with autologous stem cell transplantation has improved outcome and survival of patients with multiple myeloma. However, the majority of patients suffer from relapse. Using real-time quantitative (RQ) PCR we have shown before (Haematologica 89,2004) that the amount of residual tumor cells in the bone marrow of patients before transplantation is of prognostic relevance. In this study we evaluated in a larger group of patients with multiple myeloma whether a pre-transplantation level of clonotypic cells in the bone marrow is predictive for time-to-progression (TTP) and overall survival (OS). Further, we compared results with known prognostic factors. Patients and Methods: Bone marrow samples of 19 patients with stage II/III multiple myeloma were obtained after induction therapy but before transplantation. Immunoglobulin heavy chain (IgH) RQ-PCR using patient-specific Taqman probes was performed to quantify pre-transplantation tumor levels. The proportion of clonotypic cells was assessed as IgH/2 beta-actin ratio in percent. Medical records of patients were reviewed for prognostic factors and outcome. Results: The median level of residual tumor cells in bone marrow of all patients at the time before transplantation was 0.3 %. At 23 month median follow-up after transplantation the median TTP and OS in our study were 14 and 36 month, respectively. The threshold level of 0.03% clonotypic cells identified two prognostic groups (p&lt;0.0001, log rank). Twelve patients in the bad prognostic group had an early relapse with a median TTP of 9 month (range: 3 – 17 month). All patients in the good prognostic group (n=7) had ongoing remissions after a median follow-up of 24 month (range: 13–44 month). Univariat analysis was performed including other prognostic factors at the time before transplantation such as cytogenetic abnormalities, beta2-microglobulin, hemoglobulin, platelet count, LDH, CRP, serum albumine and age. Besides the pre-transplant level of minimal residual disease, CRP level was predictive for TTP. In multivariat analysis using a step-wise cox regression model grouping by pre-transplantation tumor level was the only prognostic factor for TTP (p = 0.05). Moreover, low pre-transplantation tumor levels also showed a trend for a better OS, but in multivariat analysis only normal cytogenetics were predictive for a superior outcome (p = 0.03). Conclusion: Quantitative molecular assessment of pre-transplantation tumor level in the bone marrow is an independent prognostic parameter for the progression-free survival of patients with multiple myeloma and thus helps to guide therapeutic interventions


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3389-3389 ◽  
Author(s):  
John D. Shaughnessy ◽  
Jeffrey Haessler ◽  
Jerry Zeldis ◽  
Yongsheng Huang ◽  
Fenghuang Zhan ◽  
...  

Abstract Background: THAL, whose activity in MM was discovered in the setting of advanced and refractory disease in the late 1990’s (Singhal, NEJM, 2000), has become the standard front-line therapy in combination with dexamethasone (DEX). In a randomized phase III tandem transplant trial, TT2, a higher complete response (CR) rate and longer event-free survival (EFS) had been observed on the THAL arm (Barlogie, NEJM, 2006). The similar overall survival (OS) on THAL and control arms had been attributed to the routine use of THAL as salvage therapy for the patients randomized to the No-THAL arm and the shorter post-relapse OS among patients randomized to the THAL arm. Patients and Methods: With a median follow-up on TT2 of 53mo, 107 patients have relapsed and 219 died. Subset analyses were performed to determine whether THAL confers an OS advantage in any subgroup of patients. Results: 6-yr EFS and OS rates are 48%/63% on THAL and 38%/58% on control arm (p=0.01/0.67). Post-relapse OS is now similar with median durations of 5.3mo/4.3mo among control/THAL arms (p=0.11). According to multivariate analyses of 11 standard prognostic factors, EFS was shorter among patients treated without THAL, in the presence of cytogenetic abnormalities (CA), B2M and LDH elevations and low albumin, whereas CR was favorable; OS was inferior with CA, high LDH, low albumin and in patients not receiving 2nd transplant or not achieving CR. Randomization to THAL was beneficial only in the >2 risk factor group: 6-yr OS was 47% in 31 patients on THAL and 12% in 31 control patients (Figure 1, p=0.01). When examined in the context of GEP (70 gene model-based high versus low risk groups) and inter-phase FISH data (amp1q21), available in 260 patients, the 57 with GEP low risk and absence of amp1q21 receiving THAL had 5-yr OS of 90% compared to 74% among 73 controls (p=0.13). Conclusion: With longer follow-up of 53mo on TT2, EFS remains superior among patients randomized to THAL; post-relapse survival is no longer inferior among those randomized to THAL; THAL benefited a high-risk subgroup with >2 standard risk factors, whereas no significant `difference has yet emerged among genetically defined subgroups. Figure Figure


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5220-5220
Author(s):  
Alvaro Moreno-Aspitia ◽  
Antony Charles ◽  
Tejal Patel ◽  
Celine Bueno ◽  
Abba Zubair ◽  
...  

Abstract Background: IgM multiple myeloma (MM) are very rare plasmaproliferative disorders representing 0.5–1.2% of all cases of MM and &lt; 0.2% of all IgM monoclonal gammopathies. Clinical criterion are not always helpful in differentiating IgM MM from Waldenstrom macroglobulinemia. However, the presence of lytic bone lesions, absence of lymphadenopathy and/or hepatosplenomegaly, presence of translocation of the immunoglobulin heavy chain locus at 14q32 [t(11;14), t(14;16), t(4;14)], and strong expression of CD138 by the plasma cells are useful in the diagnosis of IgM MM. It has been our experience and of others that these cases have an aggressive behavior at presentation, shorter survival than IgG and IgA MM and poor response to therapy for lymphoplasmacytoid lymphomas. We present here 2 cases of IgM MM with a dramatic response to Lenalidomide and low dose dexamethasone (Rev/Dex) Results: Baseline patient characteristics at time of diagnosis of IgM MM and therapy outcome are presented in the following 2 tables: Table 1. Case 1 2 Age and sex 72 (F) 73 (F) Serum M-spike (g/dL) 5.3 6.2 Urine M-spike (mg/dl/24 hrs) 72 412 Serum IgM (mg/dL) 8,590 11,000 BM plasma cells percentage 90 20 Plasma cell immunophenotyping CD138+++, partial CD20, CD56− CD138+++, partial CD20, CD56− Cytogenetics (Standard and/or FISH) Standard: normal FISH: not done on initial biopsy. On follow up there were insufficient number of plasma cells to perform test Standard: of 20 metaphases, 6 had a complex hypotetraploid karyotype with relative loss of 13q, 14, 15, 16, 20, and 22, and numerous unbalanced rearrangements. FISH: a plasma cell clone with monosomy 13 and IGH/c-MAF fusion, t(14;16). In addition, approximately 60% of plasma cells had a tetraploid clone with the same anomalies as well as relative loss of p53 Bone lesions Multiple non-traumatic spinal fractures and of stenum Several lytic lesions of long bones Renal insufficiency No No Anemia (Hbg g/dL) Yes (8.7) Yes (8.1) Hypercalcemia (Ca mg/dL) Yes (12.5) Yes (11.4) Beta 2 microglobulin (mg/dL) 5.79 8.51 Serum viscosity (cpoise) 5.9 4.8 Table 2. Best Response to therapy Case Therapy Best Response Comments 1 Rituxan, then Fludarabine based therapy Transient response Rapid progression after partial and transient response to each therapy 1 Lenalidomide + LD-Dex sCR after cycle #6. Currently on CR 18 months later IgM declined from 8,590 to 43 mg/dL after 4 cycles of Rev/Dex. 2 Lenalidomide + LD-Dex VGPR after cycle #2 IgM declined from 11,000 to 463 mg/dL after cycle 3. Complete disappearance of M-spike in serum; BM to be done after cycle #4 Conclusions: This is the first report that we are aware of a rapid and dramatic response to lenalidomide and low dose dexamethasone in these rare cases of IgM MM with poor response to NHL-type treatment. Lenalidomide-based therapy might abrogate poor prognosis cytogenetics in this unusual subtype of MM (case #2), however, follow up for this patient is still very short.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3095-3095
Author(s):  
Xavier Leleu ◽  
Wanling Xie ◽  
Meghan Rourke ◽  
Ranjit Banwait ◽  
Renee Leduc ◽  
...  

Abstract Abstract 3095 Introduction: Waldenstrom macroglobulinemia (WM) is a low grade B cell lymphoma characterized by the secretion of IgM protein in the serum. The IgM level lacks sensitivity due to its prolonged half-life. The serum free light chain (sFLC) assay has shown significant clinical application in plasma cell dyscrasias, specifically in multiple myeloma, and is used to monitor response to therapy. In this study, we sought to examine the role of sFLC in the response and progression of patients with WM. Methods: This study was performed using serum collected from a homogeneous cohort of patients diagnosed with WM and uniformly treated on a phase 2 trial using the combination of bortezomib with rituximab, previously untreated (N=26) or relapsed and or refractory to prior therapy (N=37). Patients eligible for this analysis must have measurable sFLC levels at baseline. A total of 48 patients were included. FLC response is defined as achievement of normal iFLC value or 50% decrease from baseline in the iFLC level during therapy and follow-up. Concordance between FLC and IgM response rate was evaluated using Kappa statistics. Correlation was evaluated using Spearman correlation coefficient. Time to progression was estimated using Kaplan-Meier methodology. We also did landmark analysis to compare overall response rate and time to progression by FLC or IgM response status at 2 months after therapy initiation; Fisher Exact test or Log-rank test were used. Results: The median iFLC value was 103.50mg/L (range 22.5–3540), the median kappa over lambda ratio was 13.45 (0.01-665), and the median serum IgM value by nephlometry was 3995 mg/dL (537-10,800). Overall, as per M spike response criteria, 29 (60%, 90% CI: 48%, 72%) patients responded, e.g. had partial response or better, and 19 patients failed to obtain response. Using serum IgM protein measurement by nephlometry during therapy and follow up post-therapy, 35 (73%, 90% CI: 60%, 83%) patients responded with a PR or better (>50% decrease), with 3 (6%) having normalization of their serum IgM. In comparison, iFLC response during treatment and follow up occurred in 38 (79%, 90% CI: 67%, 88%): with 2(4%) having normalization of value, 21(44%) having 50% reduction and 15(31%) having both. The time to iFLC response and IgM response among patients who achieved response by both criteria was calculated (N=33). The median time to iFLC response was 2.1 months (range 0.9–28.7months), while the median time to IgM response was 3.0 months (0.9-14.7) (p=0.07). The median time to progression per the protocol was 18.9 months (95% CI:10.5-NR). The Kappa concordance between iFLC 25% increase and M spike progression was 0.63 (95% CI: 0.41–0.84). This showed a better concordance compared to using the iFLC >50% definition (kappa=0.58, 95% CI: 0.35, 0.81), indicating that progression using iFLC>25% would be a better definition for patients with WM. The median time to progression by iFLC>25% increase was 13.7 months (95% CI:10.9-19.4) and the median time to IgM >25% increase was 14.6 months (95% CI: 9.5–19.1), showing a more rapid detection of progression by iFLC compared to M spike and IgM measurements. We next examined whether attaining a response using iFLC can be a predictor of overall response to therapy. Seventeen patients (35%) achieved an iFLC response at 2 months after therapy initiation. Patients with early iFLC response were more likely to have intermediate/high ISS-WM stage, elevated B2M or low Hemoglobin<11.5 gm/dL (p<0.05). Early iFLC response was related to overall IgM response during therapy and follow up (p=0.02). In multivariable models when adjusting for ISS stage, B2M or Hgb, there was no significant association between FLC early response and TTP either by protocol, FLC or IgM criteria. However, there was trend that early response was related to prolonged TTP especially when adjusting for hgb risk factors (HRs ranges from 0.63∼0.80, p>0.3 for various TTP endpoints. Conclusion: iFLC may be a useful marker of tumor measurement that correlates well with IgM and M spike measurements. The time to iFLC response was shorter by 1 month compared to IgM or M spike measurement. The median time to progression by iFLC was shorter by 1 month compared to IgM. There was a trend that early response was related to prolonged TTP when adjusting for other risk factors. Disclosures: Leleu: Celgene: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Chugai: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; LeoPharma: Consultancy, Honoraria.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2728-2728
Author(s):  
Andrew M. Evens ◽  
Tatyana Feldman ◽  
Aimee Kroll ◽  
Lori S. Muffly ◽  
Eric Winer ◽  
...  

Abstract Abstract 2728 Background: TCLs are uncommon malignancies consisting of heterogeneous pathologic subtypes and outcomes. Despite development of prognostic models, there is little data of outcomes in large cohorts examining the impact of frontline therapy and the role of consolidative stem cell transplantation (SCT). Methods: We performed a multi-center retrospective analysis of a large cohort of newly diagnosed mature TCLs (non-cutaneous) from 2000–2010 across 9 U.S. academic centers. We examined detailed information regarding patient characteristics and treatment(s) received. Further, we determined prognostic factors for associations with survival in univariate analysis and multivariate Cox regression proportional models. Results: Among 402 cases of mature TCL, 341 had complete treatment and follow-up data. This included 107 cases of peripheral TCL (PTCL NOS), 89 anaplastic large cell lymphoma (ALCL), 77 angioimmunoblastic TCL (AITL), 23 NK/TCL, 20 acute t-cell leukemia/lymphoma (ATLL), 10 enteropathy-associated TCL (EATCL), 7 subcutaneous panniculitis-like TCL (SCPTCL), 5 hepatosplenic TCL (HSL), and 4 transformed CTCL (t-CTCL) cases. 60% of pts were men and the median age was 62 years (range 18–95). At initial diagnosis, performance status was 2–4 in 36%, B symptoms in 47%, elevated LDH in 55%, anemia in 64%, and hypoalbuminemia in 46% at baseline. 74% of pts had advanced-stage disease, 29% had bone marrow involvement, 52% had other (non-marrow) extranodal sites, and only 9% had bulky disease >7cm. Twenty-three pts received only palliative therapy all of whom survived <3.5 months. Among the remaining 318 pts, CHOP-like therapy was the most common initial regimen (74%; 5% of which included etoposide), 7% hyperCVAD/MA, 3% EPOCH, 2% CMED, 2% gemcitabine-based, 2% ifosfamide-based, and 10% other. 21% received radiation therapy (RT) as part of initial treatment, while 34 pts (11%) received a SCT in 1st remission (85% autologous). Overall response to therapy was 73% (61% complete), while 24% had primary refractory disease. With a median follow-up of 38 months (6–109), 3-year progression-free survival (PFS) and overall survival (OS) for all pts were 32% and 52%, respectively (Figure). Factors predictive of outcome by univariate analysis are detailed in the Table (includes differential survival by WHO subtype and PIT and IPI). On multivariable regression analysis of pre-treatment factors, only Ann Arbor stage I/II remained significant (PFS: HR 0.59 [95%CI 0.38–0.93], p=0.023); and OS: HR 0.46 [95%CI 0.25–0.85], p=0.013). Regarding induction treatment, the only impact based on regimens received were inferior outcomes with CMED or EPOCH therapy; these findings persisted on multivariate analysis. The addition of etoposide to CHOP did not appear to impact outcome, although those numbers were small. Notably, consolidative SCT portended significantly improved survival on multivariate analysis when controlling for gender, LDH, albumin, and stage (PFS: HR 0.46 [95%CI 0.24–0.89], p=0.02; and OS: 0.43 [95%CI 0.19–0.99], p=0.04), but this did not reach significance when adjusting for response to 1st therapy (PFS: HR 0.55 [95%CI 0.28–1.08], p=0.08; OS: HR 0.47 [95%CI 0.17–1.29], p=0.14). Conclusions: In this large US cohort of TCL, response, PFS, and OS compared favorably with historical controls. Further, we documented that NK/TCL, AITL, and ALCL (ALK+ and negative) were all associated with improved OS vs PTCL NOS. On multivariable analysis, limited-stage disease was the predominant predictive factor for survival. Additionally, consolidative SCT was associated with improved PFS and OS, however this benefit appeared to be nullified after controlling for initial response. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5380-5380 ◽  
Author(s):  
Julie L Tarant ◽  
John Ashcroft ◽  
Sylvia Feyler ◽  
Roger G Owen ◽  
Christopher Parrish ◽  
...  

Abstract Background In recent years, the introduction of the immunomodulatory drugs (IMiDs) thalidomide & lenalidomide & the proteasome inhibitor (PI) bortezomib has substantially improved the therapeutic options & prolonged survival of patients (pts) with multiple myeloma (MM). Current treatment strategies involve sequential exposure to these agents, though the most effective sequencing of exposure has yet to be determined. MM is still, for the majority of pts, a relapsing & incurable disease with poor survival outcomes & alternative treatment approaches in relapsing disease after exposure to currently available novel agents is an on-going unmet need. We report the results of extended follow-up in this patient cohort. Objectives We examined outcomes in pts with progressive disease following sequential exposure to thalidomide, bortezomib & then lenalidomide, to assess responses to these & subsequent therapies in a “real-life” single centre setting. Methods Pts were eligible for this retrospective study if they had received sequentially thalidomide-, bortezomib- then lenalidomide-based combination therapy (LenCom) for MM as per The National Institute for Health & Care Excellence (NICE) guidance. Case records were examined for diagnostic details, depth & duration of response to PI treatment & regimens employed. T0 was defined as the time point at which LenCom was discontinued, whether for progressive disease (PD) or intolerance (I). Response to therapy subsequent to T0& Progression Free Survival/Overall Survival (PFS/OS) were assessed & factors predicting outcome analysed (e.g. ISS stage at diagnosis, age, previous therapies received, previous depth & length of response to treatment). Results Between Jan’07-Sept’12, 55 pts (27 Male & 28 Female) were enrolled. Median age at diagnosis was 59 yrs (range 33-89);ISS scores were: 20% stage I, 28% stage II & 28% stage III (23% unclassified). The median number of lines of therapy prior to LenCom was 3 (range 2-6). First line therapy was thalidomide-based in 64%; 36% underwent ASCT & 4 pts underwent tandem ASCT/RIC AlloSCT. Second line therapy was bortezomib-based in 42% &  53% pts received lenalidomide as > 4th line. Median time from diagnosis to commencing LenCom was 52.5mns (range 4-146). 43 pts (77%) had reached T0 (PD n=29, I n=14). At a median of 66 mns follow up (range 12-162 mns), a median of 9 cycles (range 1-32) of LenCom were administered to all pts & 7 cycles (range 1 -32) to those who had discontinued LenCom. Dexamethasone was discontinued after median 12 cycles in pts reaching T0, being stopped in 28% (median 6 cycles before T0). Median PFS from commencement of LenCom was 16.2 mns. At 4 mns median follow-up post T0, a total of 26 pts have received therapy after T0, of whom 3 received lenalidomide-based treatment (11.5%) & 3 received bortezomib-based treatments (11.5%). Thalidomide based treatment was received by 13 pts (combined with Bendamustine in 3 & bortezomib in 2). Post-T0 pts also received clinical trial therapies (3 pts on SRT501 trial, 1 pt on pomalidamide companion study & 1 pt on KW2478 – a heat shock protein 90 inhibitor), thalidomide-based treatment (10 pts, 2 with bortezomib), & high dose dexamethasone. 13 pts (50%) demonstrated PD as maximum response to first post-T0 therapy. Duration of response was generally very limited (median 0 mns, range 0-6 mns). Second line post T0 treatments, including pomalidomide, were received by 12 pts with only 2 pts pts achieving a PR or better to Thalidomide & bortezomib based regimens. Third line post T0 treatments were given to 2 pts with 1 pt achieving a further brief PR to DT-PACE. With a median follow-up of 6.4mns (1-37), 31 pts have died (PD n=18, infection n=6, other n=7). Median OS from diagnosis & commencement of LenCom were 100 mns & 18.4 mns, respectively. Median OS from T0 was 3.9mns (range 0-33 mns), influenced by the b2-microglobulin at T0 (<vs.³ 3.0 mg/L: 9 vs. 4.8 mns, p=0.027). The depth of response to LenCom correlated with PFS (P<0.001) but not post-T0OS (p=0.68). Conclusion Pts with MM who have relapsed after sequential exposure to thalidomide, bortezomib & lenalidomide have very limited treatment options. At present, a wide range of treatments are used, including re-challenging with lenalidomide, bortezomib & trial based treatments. However, few pts achieve a meaningful response to therapy & survival is consequently extremely poor. Disclosures: No relevant conflicts of interest to declare.


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