Treatment Patterns & Survival In Multiple Myeloma Patients Sequentially Exposed To Thalidomide, Bortezomib & Lenalidomide In a UK Single Centre

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5380-5380 ◽  
Author(s):  
Julie L Tarant ◽  
John Ashcroft ◽  
Sylvia Feyler ◽  
Roger G Owen ◽  
Christopher Parrish ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Response To Therapy ◽  
High Dose ◽  
Second Line ◽  
Single Centre ◽  
Line Therapy ◽  
Wide Range ◽  
Duration Of Response

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.

The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2892-2892
Author(s):  
Claudia Crippa ◽  
Samantha Ferrari ◽  
Monica Drera ◽  
Marinella Calarco ◽  
Antonio Regazzoli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nizar M. Tannir ◽  
Robert J. Motzer ◽  
Elizabeth R. Plimack ◽  
David F. McDermott ◽  
Philippe Barthelemy ◽  
...  
Keyword(s):  
Risk Groups ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Post Hoc ◽  
Study Dose ◽  
Clinical Trial Information

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]

Achievement of CR and nCR Before and After First High-Dose Therapy Followed by Autologous Stem Cell Transplantation Is a Major Marker for Long-Term Survival in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3400-3400
Author(s):  
Hartmut Goldschmidt ◽  
Gerlinde Egerer ◽  
Ute Hegenbart ◽  
Markus Munder ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Significant Prognostic Factor ◽  
High Dose Therapy ◽  
Free Survival ◽  
Before And After ◽  
Duration Of Response

Abstract Abstract 3400 Poster Board III-288 To analyse the impact of complete response (CR), near CR (nCR) and very good partial response (VGPR) before and after first high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) on overall survival (OS) and progression-free survival (PFS), we evaluated all patients with multiple myeloma (MM) who underwent an ASCT in frontline treatment at our centre. The transplantations were performed between June 1992 and February 2009 giving a minimum follow up of 5 months after ASCT. The retrospective analysis included a total of 994 patients (579 males and 415 females) with a median age of 58 years at time of first ASCT (range 25 - 76 years). Median follow-up after first ASCT was 5.8 years. All patients suffered from symptomatic MM. Before induction treatment 48%, 31% and 21% of patients were in ISS-stage I, II and III, respectively. The following induction regimes were applied prior to HDT: VAD (n=683), TAD (n=74), PAD (n=64), and other regimes (n= 173). The patients were treated with HDT once (n= 460), twice (n=437) or thrice (n=97). 91 patients received an allogeneic SCT, 30 of these before first progression after ASCT. These were censored for PFS at time of allogeneic SCT. Maintenance therapy (interferon n=332, thalidomide n=203, bortezomib n=48 or others n=13) was administered in 596 patients. Overall survival and progression-free survival were calculated from the time of first ASCT. The median OS time was 5.7 years and the median PFS was 2.2 years. Log-rank test, univariate and multivariate Cox PH regression as well as landmark analyses were utilized to assess the prognostic impact of response. We analysed the effect of achievement of CR, of nCR or CR and of VGPR or CR or nCR before and after HDT, respectively. Achieving CR or nCR is a highly significant prognostic factor for PFS and OS before (p<0.001 and p=0.01, respectively) and after first HDT (both p<0.001). The group including VGPR showed superior outcome when assessed after HDT, driven by the effect of CR/nCR. When adjusting for the effect of age, beta-2 microglobulin before ASCT, albumin before ASCT, new drugs before ASCT (thalidomide and bortezomib; yes/no), second ASCT within 9 months (yes/no), maintenance therapy (yes/no), and date of first ASCT, achieving CR or nCR remained a significant prognostic factor (PFS after ASCT: HR=0.66 [0.54;0.80], p<0.001; OS after ASCT: HR=0.65 [0.51;0.83], p=0.001). In addition, we analyzed the effect of duration of response compared to response achievement per se. Patients who sustained their remission (overall response = PR and better) at 3 yrs after first ASCT had a favourable prognosis with respect to OS compared to patients losing remission. Conclusion: In our single-center cohort achieving CR or nCR before and after first HDT is highly prognostic for PFS and OS in MM. Sustained duration of response is also associated with an improved prognosis (3 years landmark analysis). At our centre we recommend that patients not achieving at least an nCR should be treated with a second cycle of HDT. Disclosures: No relevant conflicts of interest to declare.

Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1790-1790
Author(s):  
Petra Obrtlikova ◽  
Anna Jonasova ◽  
Magda Siskova ◽  
Eduard Cmunt ◽  
Adela Berkova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

Use of Alkylating Agents Among Patients with Multiple Myeloma in a National Registry, 2006-2008.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4941-4941
Author(s):  
Carla M Van Bennekom ◽  
Theresa E Anderson ◽  
Noopur Raje ◽  
Kenneth C Anderson ◽  
David W Kaufman
Keyword(s):  
Multiple Myeloma ◽  
Median Duration ◽  
Research Funding ◽  
Alkylating Agents ◽  
Initial Therapy ◽  
Novel Agents ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Abstract 4941 Background While alkylating agents were among the earliest treatments for multiple myeloma, newer therapies have been available for several years. Here we describe patterns of use and effectiveness of alkylators in the modern landscape of myeloma treatment, based on a nationwide registry of recently diagnosed patients. Methods The “Patient Registries at Slone: Myeloma” is a national disease-based observational registry conducted by Boston University. All patients with myeloma diagnosed within 4 months of enrollment were eligible for inclusion. Subjects enrolled by mail or over the internet; information on treatment, clinical events, and quality of life was obtained by questionnaire and from medical record review at baseline and at six-month intervals. There were 342 patients with multiple myeloma residing in 43 states who were enrolled from June 2006-October 2008 and completed at least a baseline questionnaire. The median length of follow-up was 8 months after diagnosis (range 0.5-24). Results Alkylators were used as initial treatment in 26 patients (8%), as second-line treatment in 14 (4%), and as part of a transplant regimen in 76 (22%). Patients who received alkylators as initial or second-line therapy tended to be older (median age, 69 vs. 60 years, p<0.0005), and the combined prevalence of use was 17% among patients who did not have prescription drug insurance, compared with 11% among those who did (p=0.36). The prevalence of first-line use was 12% among patients diagnosed in 2006, 9% in 2007, and 4% in 2008 (p=0.09). Further results are confined to 34 of the 40 first or second-line alkylator recipients for whom medical records were available. The regimens used are shown in the table; the majority of patients received regimens that included melphalan. The median duration of initial therapy was 3 months (range 0.5-15); 6 patients (24%) had at least a partial response. Ten patients were still on treatment at the end of follow-up; in 15 (60%), alkylator therapy was changed to another regimen (11) or stopped without new therapy during the follow-up period (4), including 3 due to insufficient response and 5 due to toxicity. The new regimens were thalidomide-based in 2 patients, bortezomib-based in 3, bortezomib+lenalidomide in 1, dexamethasone without novel agents in 2, and 3 patients went directly to autologous stem-cell transplant. Second-line therapy with alkylators was initiated due to insufficient response from the previous regimen in 2 patients, because of side effects in 5, and for cost reasons in 2. The median duration was 2 months (range 0.5-12, with 4 patients still on treatment), and 4 (44%) had a partial or better response. The immediately preceding regimen was thalidomide-based in 5 patients, lenalidomide-based in 1, and bortezomib-based in 3; the median number of previous regimens was 2 per patient (range, 1-4). The median duration of previous therapy was 4 months (range 0.5-9). Conclusions The present population-based results indicate that in the modern era of myeloma treatment, the most prevalent use of alkylating agents is as conditioning for stem cell transplants; the drugs are also still used for initial treatment, mostly in combination with novel agents, although the prevalence was low overall and continued to decline during 2006-2008. Patients who received alkylators for initial or second-line therapy were older and the agents appeared to be somewhat more commonly used among those who did not have prescription drug insurance. The data suggest that there continues to be a useful role for alkylating agents as initial therapy, particularly for myeloma patients who are not transplant candidates, and occasionally as an early replacement for novel agents that prove ineffective or excessively toxic in individual patients. With a relatively short duration of follow-up, there was little information on the use of alkylators in the relapsed setting, where their high level of anti-myeloma activity might be expected to lead to more use. Disclosures Van Bennekom: Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Anderson:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Raje:Celgene: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding. Anderson:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Kaufman:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding.

scholarly journals An Interim Analysis of the Turkish Myeloma Registry Among the Patients Who Have Received up to Two Lines of Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4730-4730
Author(s):  
Omur Gokmen Sevindik ◽  
Zubeyde Nur Ozkurt ◽  
Can Boga ◽  
Sevgi Kalayoglu Besisik ◽  
Yildiz Ipek ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Main Concern ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
High Risk Disease ◽  
Frontline Therapy

Abstract Introduction: To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy. Methods: Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 532 patients were included in the study, and 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone combination (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), and bortezomib lenalidomide and dexamethasone combination (VRd) (7.1%). Overall response rates (a better response than stable disease according to IMWG response assessment criteria) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p&lt;0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings. Conclusion: As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real- world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and re-imbursement of the current standard of care options. Disclosures No relevant conflicts of interest to declare.

scholarly journals Lenalidomide Maintenance Does Not Negatively Impact Overall and Progression Free Survival Using Lenalidomide-Based Regimens for Multiple Myeloma in First Relapse

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5643-5643 ◽  
Author(s):  
Hannah Cherniawsky ◽  
Zack M. Breckenridge ◽  
Irwindeep Sandhu ◽  
Michael P. Chu ◽  
Joanne D. Hewitt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Research Funding ◽  
Second Line ◽  
Second Line Therapy ◽  
Aggressive Disease ◽  
Line Therapy ◽  
First Relapse ◽  
The Impact

Abstract BACKGROUND Outcomes in multiple myeloma have improved dramatically over the last decade however, optimal sequencing of therapy remains unknown. Specifically, in an era where post-transplant lenalidomide (L) maintenance is now as established standard of care, questions remain around the utility of full dose L-based regimens in second line therapy. In this series, we sought to evaluate the impact of different regimens used at first relapse in patients who received autologous stem cell transplant (ASCT) in the frontline setting treated with and without lenalidomide maintenance (LM). We focused on the impact of L-based therapies in patients relapsing on LM. METHODS Using our prospectively maintained institutional MM database we retrospectively analyzed patients treated at the Cross Cancer Institute from January, 2005 to January, 2016 to ensure 2 years of follow-up for surviving patients. 4 categories were identified based on 2 variables: receipt of LM following 1st line therapy (yes or no) and receipt of L-based 2nd line therapy (yes or no). The primary endpoint was 2nd PFS defined as time of initiation of second line therapy to relapse, death or last follow-up. OS was defined as time of initiation of first line induction therapy to death or last follow-up. Second OS was defined as time of initiation of second line therapy to death or last follow-up. Survival statistics were determined using the Kaplan-Meier method with SPSS software. A p - value of <0.05 was considered significant. RESULTS 213 patients received standard bortezomib-based induction and ASCT of which 132 (62%) received LM. Median follow up for the LM patients was 48 months compared to 74.6 months in non-LM patients. 103 patients (48%) required treatment with second line therapy. Forty-four percent patients were treated with LM while 56% were not. Sixty-nine percent received L-based therapy at relapse, 21% received PI-based therapy and 8% were treated with a PI-IMID combination (table 1). Focusing on the cohort of relapsed patients who received LM (n=44), the median 2nd PFS was 9.3 months in those that received L-based second line therapy vs 4.1 months in those that did not (p = 0.28, figure 1b]. In patients who did not receive LM (n = 55) the median 2nd PFS was 14.0 months in those who received L-based second line therapy vs 6.9 months in those who did not (p = 0.19, figure 1a. Examining all patients who received L-based therapy at relapse there was no difference in 2nd PFS based on whether LM was given (p = 0.42). The median 2nd OS was not statistically significant between the groups (p = 0.39, figure 1b. Patients on LM had a median 2nd OS of 34 months with L-based therapy at relapse compared to 39.2 months without. The median 2nd OS in non-LM patients was 34.5 months in those receiving L-based therapy at first relapse and 23.4 months in those that did not (p=0.10). There was no statistically significant differences in median OS between the 4 groups (p = 0.83). For patients who received LM the median OS was not reached in those receiving L-based therapies at relapse and was 78.1 months in patients who did not. In patients who did not receive LM the median OS was 78.0 months in those receiving L-based therapies at relapse and 69.3 months in those who did not. CONCLUSION Our data suggests that receiving LM does not negatively impact survival outcomes after receiving full dose L-based therapy at relapse. Both median 2nd PFS and 2nd OS were similar with L-based therapies regardless of prior LM. While the 2nd PFS at relapse does fall short of recently published trials in relapsed MM there are some notable confounders here. Firstly, this real-world data includes frailer patients with potentially greater co-morbidities possibly influencing choice and duration of therapy as well as reflect more aggressive disease biology. Secondly, given the relatively short median follow-up of the relapsed LM patients to date, the cohort may be enriched with "early" relapsers (< 2-years) also potentially indicative of biologically more aggressive disease. As such, this may underestimate the true impact of L-based therapies in patients relapsing on LM. Larger series with longer follow-up are necessary to formally examine whether multi-agent L-based regimens confer additional benefit over L-Dexamethasone or non-L based regimens. Real world registries will be useful as prospective trials are unlikely to be done. Disclosures Sandhu: Novartis: Honoraria; Bioverativ: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.

Rituximab + IEV/MINE Second Line Approach in Relapsed/Refractory Non Hodgkin Lymphoma (NHL): Efficacy and Safety

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4954-4954
Author(s):  
Velia Bongarzoni ◽  
Barbara Anaclerico ◽  
Paola Anticoli Borza ◽  
Michele Cedrone ◽  
Anna Chierichini ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Second Line ◽  
High Dose Therapy ◽  
Who Grade ◽  
Dose Therapy ◽  
Cd 34 ◽  
Line Therapy

Abstract Background. Relapsed/refractory high grade NHL is a very aggressive pathology characterised by a poor prognosis. High dose therapy followed by peripheral blood stem cell (PBSC) rescue is to date the gold standard therapy. The results of high dose therapy are influenced by remission status after II line therapy as patients who undergo transplantation in complete response have better progression free survival with respect to those in partial response. While Rituximab+chemotherapy has become the approach of choice in 1st line-therapy, this type of schedule has not yet been largely applied in 2nd line therapy. In the aim of testing the efficacy of 2nd line-combined immuno-chemotherapy we designed a protocol including Rituximab + IEV/MINE. Methods. The planned treatment consists of 3 cycles of IEV or MINE (&gt;65 y patients), plus Rituximab (375 mg/sqm) given on day +1 and on day +14 every cycle. G-CSF was administered from day 7 to ANC recovery and was continued until the CD 34+ collection after the third cycle. From April 2002 to July 2008 30 consecutive patients – 19 males and 11 females, median age 57 y (range 21–73 y) with refractory (12) and relapsed (18) Diffuse Large B Cell Lymphoma (DLBCL) entered the study. According to IPI score 20/30 patients were intermediatehigh risk; 21/30 had extranodal disease. Results. 27 patients completed treatment and are evaluable; 3 pts are not evaluable because of lethal infection after Ist cicle (2pts) and lost to follow up (1pt). 21/27 (78%) were responders: 12 (44%) achieved CR, 9 (33%) PR, while 6 progressive disease (PD) were withdrawn. Hematological toxicity including WHO grade III or IV neutropenia, anemia and thrombocytopenia was recorded in 19, 8 and 14 pts, respectively. Target CD 34 harvest was reached in 19/27 (70%) pts with CD 34+ median value 7,03 × 106/Kg. Among the responders 4 pts failed CD 34 harvest. 17/27 (63%) patients underwent transplantion, 11 autologous stem cell transplantation (ASCT) and 6 (&gt;60 y) reduced intensity allogeneic-SCT. Of transplanted patients 4 (2 in CR post Mini Allo-SCT, 2 in relapse post ASCT) died 6, 2,10 and 10 months after transplantation, respectively. The remaining 13 (4 mini-alloSCT and 9 ASCT) are alive in CR which is lasting for 23 months median time (11–73). As of July 2008 15/27 (55%) patients are alive: 14 CR and 1 PR. Median follow up post R-IEV/MINE is 28 months (range 12–77), PFS was 38% and median OS is 32 months (range 7–90). Conclusions. Our experience, if limited to a small series of patients, shows that the addition of Rituximab to second line chemotherapy: increases response rate even in adverse IPI score cases, allows to obtain a good CD 34 harvest, represents an effective in vivo purging agent.

Real World Experience of Clinical Profile and Outcomes of Autoimmune Hemolytic Anemia: Single Centre Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4814-4814
Author(s):  
Ram V Nampoothiri ◽  
Uday Yanamandra ◽  
Alka Khadwal ◽  
Gaurav Prakash ◽  
Deepesh P. Lad ◽  
...  
Keyword(s):  
Haemolytic Anaemia ◽  
Real World ◽  
Conflicts Of Interest ◽  
Response To Therapy ◽  
Autoimmune Haemolytic Anaemia ◽  
Second Line ◽  
Single Centre ◽  
Cold Agglutinins ◽  
Line Therapy ◽  
Steroid Dependent

Abstract Background: Autoimmune haemolytic anaemia (AIHA) is a relatively uncommon condition for acute fall in haemoglobin with grave consequences if not diagnosed and treated promptly. The literature on the clinical outcome, response to treatment, and occurrence of acute complications is relatively scarce from the real world. Aim: We retrospectively analysed 100 cases of autoimmune haemolytic anaemia (AIHA) for clinic-pathological features and response to therapy. Patients and methods: It is a single centre retrospective analysis of all cases of AIHA managed at our centre from Jan 2010- June 2016. Patients were analysed for the demographic features, presenting complaints, clinical/ pathological findings at diagnosis, types of therapy given and response to therapy. AIHA was diagnosed by features suggestive of haemolysis (anaemia with unconjugated hyperbilirubinemia, raised LDH and reticulocytosis) and/or positive DAT in the absence of any underlying secondary causes for anaemia according to the monospecific-DAT results and the thermal characteristics of the autoantibody, patients were classified as warm AIHA (DAT positive for IgG with or without C3D), cold agglutinin disease (DAT positive for C3D only with cold agglutinins), mixed (DAT positive for IgG and C3d with coexistence of warm autoantibodies and high titre cold agglutinins), or atypical AIHA (either DAT negative). Based on the severity of anaemia, patients were classified into very severe (Hb≤60gm/L), severe (Hb-61 to 80gm/L), moderate (Hb-81 to 100gm/L) and mild (Hb>100gm/L). Results: A total of 100 consecutive patients were included fulfilling the inclusion criteria. The median follow-up of the study population was 17.7months (mean - 28.2m, range-0.3-197m). The median age of the patients was 33y (mean 36.3y: range 13-80y). There was female predominance (n=64, 64%). Easy fatiguability (85%) followed by dyspnoea on exertion (75%) were commonest presenting complaints. The median duration of complaints was 3 months (mean 8.93: range 0.2- 96). Jaundice (58%) and cola coloured urine (11%) were other important manifestations. Preceding history suggestive of viral infections was present in 22% of the patients and only one patient had significant drug history temporally correlating with AIHA. Splenomegaly was present in 67% with a median palpability of 2cm (mean 2.71: range 0- 20) and hepatomegaly in 49% with a median palpability of 1cm (mean 1.402: range 0 - 8) below the coastal margin. Lymphadenopathy was present in 8% of the patients. On severity grading 67% had very severe anaemia, 21% had severe, 9% moderate anaemia and 1% had mild anaemia. 24% of the patients had simultaneous low platelet counts less than 1 lakh. 17% patients had atypical AIHA - DAT negative. 21% patients had secondary AIHA of which eight patients had simultaneous low platelets (suggestive of Evans). The commonest cause for the secondary AIHA was rheumatological disorders (SLE 15 patients, MCTD one patient) followed by lymphomatous disorders in rest. Most common therapeutic modality employed was corticosteroids (methyl prednisolone pulse therapy n-20, prednisolone n-67), followed by IvIg (n-4), chemotherapy (RCHOP-1, RCVP-1, CVP-1) and rituximab (100mg/wk - 1, 375mg/m2/wk - 2). 75% of the patients had some clinical response (CR 47%, PR 22%, SD 6%) to the first line therapy. The median time to response was 1.5 months. 52% of the patients required repeat therapy in the form either steroid-sparing agent, immunosuppressant or repeat course of steroids. Six patients required splenectomy. The response to second-line therapy was seen in 92% of patients (CR 31/52, PR 9/52, SD 8/52). More than two lines/ times of therapy for non-response/relapse was required in 10% of the patients, of whom, 50% of the individuals were steroid dependent. A total of two patients succumbed to the illness (first owing to tuberculosis possible exacerbated by immunosuppressive therapy, and second due to progressive disease). Limitations of the study: All limitations of a retrospective study are applicable to our study as well. The selection of patients with fairer prognosis can explain a lower mortality in our study. Conclusion: Primary AIHA is the commonest form of AIHA. Most secondary AIHA has rheumatological etiology. Response to steroids is good leading to considerable remission but which is not long lasting and majority requiring second line/ second time therapy with same or alternative agents. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of Autologous Transplantation on PFS2 in Myeloma Patients Receiving Front-Line Bird (clarithromycin, lenalidomide, dexamethasone)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5778-5778
Author(s):  
Ekta Aneja ◽  
Adriana C Rossi ◽  
Tomer M Mark ◽  
David Jayabalan ◽  
Roger Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Line Therapy ◽  
Progression Of Disease

Abstract Background: BiRd (clarithromycin, lenalidomide, dexamethasone) combination therapy yields >90% overall response rates in newly diagnosed patients with symptomatic multiple myeloma (MM). Long term follow up of the phase II BiRd study revealed 49% of patients went on to receive autologous hematopoietic stem cell transplants (ASCT), either as consolidation or salvage. Here we evaluate progression free survival 2 (PFS2) and overall survival (OS) in our cohort of patients, and assess the impact of ASCT. Methods: Seventy-two patients with newly diagnosed MM were enrolled on the BiRd trial between Dec 2004 and Nov 2006. BiRd is lenalidomide 25mg PO daily (d1-21), clarithromycin 500mg PO BID, dexamethasone 40mg PO weekly, for 28 day cycle. Patients remained on BiRd until progression of disease, consolidation with autologous stem cell transplant (ASCT), or unacceptable toxicity, and all continued to be monitored through subsequent lines of therapy. We performed a retrospective chart review of all patients enrolled in the BiRd trial. PFS2 was defined as the time elapsed from start of BiRd until progression of disease on 2nd line therapy. Results: With over 8 years of follow up, 6 patients remain on continuous BiRd, 28 received ASCT consolidation, and another 6 received ASCT as salvage. Nine patients died on induction therapy and the remaining patients received second line chemotherapy. Patients were stratified by no ASCT, consolidation ASCT and salvage ASCT. Median PFS2 was 98 months, 94 months, and 53 months, respectively (p<0.22). Twenty-three patients died during second line therapy. Median OS was not reached, 102 months, and 55 months respectively (p<0.92). Discussion: Advances in the treatment of patients with multiple myeloma over the past decade have introduced increasing numbers of therapeutic options, improving survival considerably. While multiple myeloma is still considered an incurable disease, patients today will likely receive several lines of therapy. The contribution and timing of each option must be considered. In our cohort of patients, receiving ASCT in the salvage setting trended toward shorter PFS, however failed to reach statistical significance. Consolidation with ASCT in our patient cohort did not translate into survival advantage. The optimal timing and utility of ASCT in the era of novel agents and increasing treatment options warrants further review, and is an area of active investigation. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Rossi: celgene: Speakers Bureau; millenium: Speakers Bureau. Mark:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Speakers Bureau. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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