Safety and Efficacy of Bortezomib and Dexamethasone (BD) in Multiple Myeloma as First-Line, Second-Line or Third-Line Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4817-4817
Author(s):  
Juan Li ◽  
Beihui Huang ◽  
Ying Zhao ◽  
Dong Zheng ◽  
Shaokai Luo
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Median Time ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Third Line ◽  
Third Line Treatment

Abstract Purpose: To compare efficacy and safety of BDbortezomib and dexamethasone in multiple myeloma as first-line, second-line or third-line treatment. Patients and methods: 18 patients(pts) treated with BD (bortezomig 1.3mg/m2 on d 1,4,8,11 and dexamethasone 20mg on d 1–4 in a 21-day cycle). Responses were evaluated by the criteria of EBMT but a nCR was included. Adverse events were graded by the WHO criteria. Results: The median age was 52.5 years, and 13 (72.2%) were male. Ig subtypes were IgG, (8 pts, 44.4%), IgA (4 pts, 22.2%), light chain (2 pts, 11.1%), and IgD (1 pts, 5.9%). Durine/Salmon staging: IIA 5.9% (1/18), IIB 5.9% (1/18), IIIA 72.2% (13/18), IIIB16.6% (3/18). BD was administered in first-line (4 pts, 22.2%), second-line (7 pts 38.9%) and third-line (7 pts, 38.9%). The median number of BD cycles was 2.5 (range, 1–6 cycles). 17 pts could be evaluated, overall response was 88.3%, including CR in 2 pts (11.7%), nCR in 5 pts (29.4%), PR in 7 pts (41.2%), MR in 1 pts(5.9%), NC in 1 pts(5.9%), PD in 1 pts(5.9%). Pts in the first-line group received a response of 100%(4/4), including nCR in 1 pts (25.0%), PR in 2 pts (50.0%), MR in 1 pts(25.0%). The second-line group received a response of 100%(7/7), including CR in 1 pts(14.3%), nCR in 3 pts (42.9%), PR in 3 pts (42.9%). Those received BD as third-line or more got a response of 66.7% (4/6), including CR in 1 pts(16.7%), nCR in 1 pts (16.7%), PR in 2 pts (33.3%). Aderse events included diarrhea 44.4% (8/18; grade IV: 2/18), thrombocytopenia 44.4% (8/18; grade III–IV: 7/18), fatigue 44.4% (8/18; grade IV: 1/18), peripheral neuropathy 33.3% (6/18, grade II:1/18), pyrexia 22.2%, infection 16.7% (3/18), headache 11.1%(2/18), parageusis 11.1%(2/18), hypotension 5.9%(1/18), hypoglycemia 5.9%(1/18) while combining with glipizide. The median time to minimum counts of platets was 14 days. The median time to most serious peripheral neuropathy appeared after treatment of 3 cycles. In 1 pts the therapy was disrupted by toxicity. Conclusion: BD demonstrated better response as first-line or second-line therapy than as third or more line therapy. Toxicities were torelated and manegable. There were no treatment related deaths.

scholarly journals Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

2020 ◽  
Vol 14 ◽  
pp. 117955492095135 ◽  
Author(s):  
Wolfgang M Brueckl ◽  
Martin Reck ◽  
Achim Rittmeyer ◽  
Jens Kollmeier ◽  
Claas Wesseler ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Synergistic Effects ◽  
Stage Iv ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Third Line Treatment

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

scholarly journals HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe

2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Cleophas Chimbetete ◽  
David Katzenstein ◽  
Tinei Shamu ◽  
Adrian Spoerri ◽  
Janne Estill ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Line Treatment ◽  
Second Line ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Cd4 Cell Count ◽  
Line Therapy ◽  
Third Line ◽  
Cd4 Cell ◽  
Third Line Treatment

Abstract Objectives To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir. Results Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3–5.1) and 2.6 years (IQR, 1.6–4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728–208 920 copies/mL) and 201 cells/mm3 (IQR, 49–333 cells/mm3). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years (P = .003) and CD4 cell count <200 cells/mm3 (P = .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69–13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months. Conclusions The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

scholarly journals Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e022293 ◽  
Author(s):  
Jason C Hsu ◽  
Chen-Fang Wei ◽  
Szu-Chun Yang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Interrupted Time Series ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

InterventionsTargeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008.ObjectivesThis study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies.SettingWe retrieved 2004–2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database.Design and outcome measuresUsing an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment.ResultsTotally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007–2008 and following gefitinib as the first-line treatment in 2011.ConclusionsThe changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.

Risk of Progression and Survival in Newly Diagnosed Multiple Myeloma Patients Non-Responsive to Bortezomib-Based Induction Therapy: an Observational Multicenter International Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3488-3488
Author(s):  
Yael C Cohen ◽  
Erel Joffe ◽  
Noam Benyamini ◽  
Meletios A. Dimopoulos ◽  
Svetlana Trestman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Line Treatment ◽  
Second Line ◽  
Newly Diagnosed ◽  
Inclusion Criteria ◽  
First Line ◽  
Line Therapy ◽  
Induction Regimen

Abstract INTRODUCTION Botezomib-based induction is widely used and highly effective for the treatment of patients with newly diagnosed multiple myeloma (NDMM), with an overall response rate (ORR) of 75-80%. However, the outcomes of patients who fail to respond to this treatment remain unclear. The goal of this study was to investigate the outcome of patients with NDMM who failed to respond to bortezomib-based induction as compared to induction-responsive patients. METHODS We reviewed consecutive patients with NDMM between 1-JAN-2007 and 31-JAN-2014 in three participating centers in Greece and Israel. Inclusion criteria were measurable disease and an induction regimen containing bortezomib in combination with alkylators and/or corticosteroids. Patients who failed to achieve at least partial response in accordance with IMWG criteria after 4 cycles of therapy were classified as non-responsive and their baseline characteristics, next treatment, overall survival and progression following second-line treatment (2ndPFS) were assessed and compared to responsive patients. 2ndPFS was defined as the time from 2nd line treatment to disease progression, death or censoring. In the non-responsive group we limited this analysis to patients advancing to 2nd line within six months of initiation of induction. RESULTS Two hundred and ninety five patients met inclusion criteria and 74 (25%) were non-responsive to bortezomib-containing induction. Non-responsive patients were older, more anemic and had more often ISS-3, del17p and ECOG performance status 2-4 (table 1). Notably, these patients received less often a bi-weekly bortezomib schedule, a triple-drug regimen and high dose melphalan treatment at first line. Of the non-responsive patients 57% (n=42) received salvage treatment immediately following induction non-response, with an ORR of 59% (25/42); 12/31(39%) of those treated with salvage 2nd line and 13/15(87%) of those who underwent HDM at first line, responded. Failure to respond to bortezomib induction was associated with increased mortality (HR 5.06, 95% CI 2.80 – 9.16) (Fig. a), which remained significant in multivariate analysis. One- and 3-years OS in responsive vs. non-responsive patients were 97% vs 76% and 88% vs 53%, respectively (p<0.0001). 2ndPFS in patients who received salvage second line therapy immediately following induction failure was similar to that measured in bortezomib-responsive patients receiving 2nd-line therapy for disease progression, approaching 14 months. However, survival from time of salvage 2nd-line treatment was significantly lower among patients non-responsive to bortezomib-based induction compared to that measured in responsive patients (25 months vs. not reached, respectively, p=0.024; Fig. b). CONCLUSIONS Failure to respond to a bortezomib-based induction was found to be an independent risk factor for mortality. Despite the non-inferior 2ndPFS reported in these patients as compared with their bortezomib-responsive counterparts, survival remained significantly inferior. Possibly this difference is because non-responsive patients are less likely to respond to further proteasome inhibitor therapy at following relapses. Randomized controlled trials are needed to test whether intensification of induction and/or of further treatment may improve the poor prognosis of patients who fail to respond to bortezomib-based induction. Table 1: All patients n = 295 Induction non-responsive n = 74 Induction - responsive n =221 P value Demographic Median Age (yrs) 62.0 66.8 61.0 0.004 Gender Male Female 148 (50%) 147 (50%) 42 (55%) 33 (45%) 107 (48%) 114 (52%) 0.347 Patient / Disease ECOG 0-1 2-4 182 (63%) 107 (37%) 33 (45%) 40 (55%) 149 (69%) 67 (31%) <0.0001 ISS I II III 74 (28%) 95 (36%) 95 (36%) 9 (14%) 20 (33%) 33 (53%) 65 (32%) 75 (37%) 62 (31%) 0.002 High risk Cytogenietics Del17p High risk (%) Elevated LDH (%) Extramedullary disease (%) Hb≤ 10 gr% Creatinine > 2mg% 23 (14%) 69 (34%) 66 (27%) 23 (9.5%) 114 (43%) 64 (23%) 10 (26%) 13 (28%) 21 (36%) 5 (8.1%) 35 (54%) 20 (30%) 13 (10%) 56 (36%) 45 (24%) 18 (9.7%) 79 (39) 44 (21%) 0.031 0.297 0.091 0.805 0.044 0.094 Therapy Induction regimen VCD Vd VMP PAD 204 (69%) 49 (17%) 11 (4%) 19 (6%) 52 (57%) 18 (24%) 3 (4%) 4 (5%) 162 (73%) 31 (14%) 8 (4%) 15 (7%) 0.007 Any triplet 243 (82%) 55 (74%) 188 (85%) 0.051 Bortezomib schedule Bi-weekly Weekly 239 (81%) 56 (19%) 52 (70%) 22 (30%) 187 (85%) 34 (15%) 0.010 HDM at first line 143 (48%) 15 (20%) 128 (58%) <0.0001 Figure 1 Figure 1. Disclosures Dimopoulos: Celgene: Consultancy, Honoraria.

scholarly journals Disease Management and Resource Use for the Management of Melanoma stage IIIc or IV Positive for BRAF V600 Mutations in Greece

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Carayanni V ◽  
Gogas H ◽  
Bafaloukos D ◽  
Boukovinas I ◽  
Latsou D ◽  
...  
Keyword(s):  
Resource Use ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Cost Of Treatment ◽  
Management Scenario ◽  
Third Line ◽  
The Cost ◽  
Third Line Treatment ◽  
First Line Treatment

Objective: Melanoma is one of the most aggressive cancers and is responsible for the majority of skin cancer deaths, with the presence of metastases prognostic for poor survival. At a time when most cancer incidences are falling, the annual incidence of melanoma has risen as rapidly as 4-6% in many European countries, with a substantial economic burden in advanced stages. The objective of this study is the investigation of treatment pathways and healthcare resource use related to advanced BRAF-mutated melanoma in Greece. Methods: This study is based on the information collected by an expert panel comprising of 3 oncologists of major public and private melanoma clinics around Greece. A 3-round survey was undertaken, according to a modified Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Oncology drug costs, medical visits, laboratory tests, imaging examinations, hospitalization and concomitant medications were the resources considered in the context of the Greek National Services Organization (EOPYY). Results: Τhe most common management scenario (80% of cases) in Greece for patients of stage IV BRAF V600 mutated melanoma was: targeted therapies as first line treatment at 95%, followed by immunotherapies at 100% as second line as well as third line treatment at 65% of cases. The weighted annual cost of treatment was 89.215,78 €, (90%CI:62,451.05; 115,980.51) for first line treatment at list price and around 41.584,50 (90%CI:29,109.15; 54,059.85) based on the negotiated price. At second line, the cost of treatment has been estimated between 15,704.272 (90%CI:10,992.990; 20,415.553) and 19,800.92€, (90%CI: 16,489; 30,622) for the two most common management scenarios for immunotherapies. For third line treatment the cost was 37,778.93 (90%CI 26,445.25; 49,112.61€) for the mostly used management scenario (50% ipilimumab). Conclusions: Μetastatic BRAF mutant melanoma requires prolonged and costly treatment with new therapies shown to substantially increase life expectancy. Identifying the appropriate treatment options in order to optimize health outcomes should be an important priority in healthcare system.

scholarly journals Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

2020 ◽  
Author(s):  
Tetsu Tomonari ◽  
Yasushi Sato ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Yasuteru Fujino ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

AbstractBackground & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

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.

Retreatment Patterns and Outcomes Among Patients with Relapsed Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5935-5935
Author(s):  
Lincy S Lal ◽  
Benjamin J Chastek ◽  
Cori Blauer-Peterson ◽  
Eric M Maiese
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Index Date ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Risk Of Death ◽  
Line Therapy ◽  
Line Of Therapy

Abstract Introduction: Clinical trials have suggested that retreatment with multiple myeloma (MM) therapy provides clinical benefit (Mohty 2012), however, little is known about real-world utilization and outcomes of retreatment. Information from this analysis will help to better understand the real-world impact of retreatment for management of first MM relapse. Methods: A retrospective claims analysis of commercial and Medicare Advantage patients aged 18 years in the Optum Research Database. To be included, patients had to have ≥ 2 medical claims ≥ 30 days apart with an MM diagnoses (ICD-9 =203.00) between 01 Jan 2009 and 31 Dec 2013 (study period); ≥ 2 lines of therapy and no evidence of hematopoietic cell transplant during the study period and data available for 1 year prior to index date and ≥ 6 months post index date. The date of the first claim of an NCCN recommended MM treatment during the study period was considered the index date. All MM treatments identified < 30 days of the index date were considered part of first line of therapy. An algorithm was developed for identifying subsequent lines of therapy. A new line of therapy was identified when there was a switch to a new agent < 180 days of discontinuation of the prior line of therapy or retreatment with the same treatment ≥ 180 days of discontinuation with previously used agents. Additionally, patients had to be treated for relapse MM defined according to lines of therapy when 1) there was an active line of therapy ≥ 60 days long and there was a gap of ≥ 180 days from the end of the line of active therapy to the start of the next line of active therapy or 2) there was a line of therapy ≥ 180 days long and a different treatment was started, with or without a 180-day gap between discontinuation of the prior line and start of the subsequent line of therapy . The data evaluated in the analysis included baseline demographics, Quan-Charlson comorbidity scores, line of therapy, and clinical outcomes, including treatment duration and overall survival. Data were analyzed using chi-square and t-tests to compare patients with retreatment vs. treatment with a different regimen for first relapse MM (i.e. second-line therapy). Results: A total of 252 patients (mean age: 70 yrs; 48% male) were identified as having second-line treatment for relapse MM; 90 patients (35.7%) were retreated with the same regimen and 162 (64.3%) patients were treated with a different regimen. Mean Quan-Charlson comorbidity scores were equal between the two groups (p=0.585). Among the retreatment group, 48.2% were treated with monotherapy for first-line, compared to 25.2% of the different regimen group (p-value < 0.001). Dexamethasone (dex) monotherapy, bortezomib plus dex, and lenalidomide plus dex were common regimens used in retreatment, see Figure 1. Lenalidomide plus dex was also commonly used as a different regimen for second-line treatment. Additionally, dex monotherapy was significantly less likely to be used as a new therapy compared to being used as retreatment for second-line therapy (p<0.05). Conversely, bortezomib plus lenalidomide plus dex was significantly more likely to be used as a new therapy compared to being used as retreatment for second-line treatment (p<0.05). The mean length of relapse line was 161 days in the retreatment group versus 212 days in the different regimen group (p-value 0.067). The incidence rate of death was 13 events (1.43 events per 10,000 person-days of follow-up) in the retreatment group versus 22 events (1.51 events per 10,000) in the different regimen group (p=0.895). Figure 1: Second-line Treatment Regimens among Patients who Received the Same Regimen (Retreatment) vs. a Different Regimen for the Treatment of First-Relapse MM\s Conclusions: In this analysis, approximately one-third of patients were retreated with the same treatments in first-line and second-line of therapy. Patients who were retreated with the same regimen tended to have shorter duration of second-line therapy. However, risk of death did not appear to differ between the two groups. This real-world analysis suggests that retreatment in second-line may affect the time to next treatment, but may not negatively impact the overall risk of death. Reference: Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and 'retreatment' approaches in the era of novel agents. Leukemia 2012; 26: 73-85. Figure 1 Figure 1. Disclosures Lal: Optum: Employment. Chastek:Optum: Employment. Blauer-Peterson:Optum: Employment. Maiese:Janssen Scientific Affairs, LLC: Employment.

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