Lenalidomide in Combination with Dexamethasone Is More Effective Than Dexamethasone at First Relapse in Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3552-3552 ◽  
Author(s):  
Edward Stadtmauer ◽  
Donna Weber ◽  
M. Dimopolous ◽  
Andrew Belch ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
Cell Transplant ◽  
Second Line ◽  
Prior Therapy ◽  
First Relapse ◽  
Line Of Therapy

Abstract Background: High-dose dexamethasone (Dex) remains a standard therapy for relapsed or refractory multiple myeloma (MM). Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with Dex. At the interim analysis, lenalidomide/dexamethasone achieved a significant benefit over dexamethasone, providing a longer median time to progression (TTP), higher response rates, and higher CR rates. Aim: This prospective subgroup analysis of MM-009/010 was performed to determine the potential benefit of starting lenalidomide/dexamethasone at first relapse by analyzing outcomes with lenalidomide/dexamethasone versus dexamethasone among patients who had received only 1 versus > 1 prior line of therapy. Methods: Patients who had received at least 1 prior treatment and were not refractory to dexamethasone were randomized to either receive oral lenalidomide (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on Days 1–4, 9–12, 17–20 every 4 weeks for 4 months, then 40 mg on Days 1–4 every cycle thereafter) or placebo plus Dex. The European Blood and Marrow Transplantation criteria were used to evaluate response. Randomization was stratified at entry by number of prior therapies (1 versus > 1). Results: Among the 248 patients who had received only 1 prior therapy, those receiving second-line lenalidomide/dexamethasone had a significantly longer median TTP (71 vs. 20 wks) and a higher response rate (complete response [CR] + partial response [PR]; 65% vs. 26%) versus those receiving second-line dexamethasone. Among the 456 patients who had received > 1 prior line of therapy, the median TTP (41 vs. 20 wks), response rate (58% vs. 20%) were higher with lenalidomide/dexamethasone compared with dexamethasone. Comparing patients who received lenalidomide/dexamethasone as second-line versus as later salvage therapy, the median TTP appeared longer and the response rates higher in patients who received lenalidomide/dexamethasone earlier, although TTP and response rates were also significantly better with lenalidomide/dexamethasone than with dexamethasone in patients who received lenalidomide/dexamethasone later. Differences in the groups included prior stem cell transplant (66% vs. 54%), thalidomide (12.5% vs. 53.2%), and bortezomib (0.4% vs. 11.6%) in the second-line versus later salvage therapy groups. No difference was observed in grade ¾ adverse events or survival with a median follow-up of 16.8 months. Conclusions: Lenalidomide/dexamethasone provided higher response rates and improved TTP compared with dexamethasone at first relapse and beyond. Response to lenalidomide/dexamethasone was superior to that to dexamethasone regardless of the type of prior therapy. TTP and response rates appeared more favorable when lenalidomide/dexamethasone was administered earlier at first relapse compared with its use as later salvage therapy. These data support the use of lenalidomide/dexamethasone for patients as second-line therapy.

Lenalidomide (Len) in combination with dexamethasone (Dex) is more effective than Dex alone at first relapse and provides better outcomes when used early rather than as later salvage therapy in relapsed multiple myeloma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7600-7600 ◽  
Author(s):  
E. A. Stadtmauer ◽  
D. Weber ◽  
M. A. Dimopoulos ◽  
I. Borrello ◽  
J. F. San-Miguel ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Response Rates ◽  
Hazard Ratio ◽  
High Dose ◽  
Prior Therapy ◽  
Line Therapy ◽  
First Relapse ◽  
Immunomodulatory Drug ◽  
Line Of Therapy

7600 Background: High-dose Dex remains a standard therapy for relapsed or refractory MM. Lenalidomide is a novel, oral, immunomodulatory drug (IMiD) that has activity against MM with additive effects when combined with Dex. At the interim analysis of MM-009/010, Len/Dex achieved a significant benefit over Dex, providing a longer median TTP, higher response rates, and higher CR rates. Aim: This prospective subgroup analysis was performed to determine the potential benefit of starting Len/Dex at first relapse by analyzing outcomes versus Dex among patients (pts) who had received only 1 versus >1 prior line of therapy. Methods: Pts who had received 1–3 prior treatments and were not refractory to Dex were randomized to either oral lenalidomide (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on Days 1–4, 9–12, 17–20 every 4 weeks for 4 months, then 40 mg on Days 1–4 every cycle thereafter) or placebo plus Dex. The EBMT criteria were used for response. Randomization was stratified at entry by number of prior therapies (1 versus > 1). Results: Of 692 randomized pts, 241 pts (34%) received only 1 prior therapy. Those receiving 2nd-line Len/Dex had a significantly longer median TTP (66 vs. 20 wks) and a higher RR (CR + PR); (63% vs. 26%) versus those receiving 2nd-line Dex. After a median follow-up of 12.1 mos for all pts, 2nd-line Len/Dex provided significantly improved overall survival (OS) (hazard ratio 1.85, P = 0.03) versus 2nd-line Dex. Among the 451 pts who had received > 1 prior line of therapy, the median TTP (44 vs. 20 wks), RR (57% vs. 20%), and OS (hazard ratio 1.50, P = 0.03) were higher with Len/Dex vs. Dex. Response to Len/Dex was superior to that of Dex regardless of the type of prior therapy. Comparing pts who received Len/Dex as 2nd-line versus later salvage therapy, the median TTP was longer and response rates higher in pts treated in second-line. Conclusions: Len/Dex provided higher response rates and improved TTP compared with Dex at first relapse and beyond. TTP and response rates were superior when Len/Dex was administered earlier at first relapse compared with its use as later salvage therapy. These data support the use of Len/Dex for pts as 2nd-line therapy for relapsed MM. [Table: see text]

Comparison of lenalidomide plus dexamethasone therapy used at first relapse versus later salvage therapy in relapsed or refractory multiple myeloma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8594-8594
Author(s):  
E. A. Stadtmauer ◽  
D. M. Weber ◽  
R. Nieszvizky ◽  
A. Belch ◽  
H. M. Prince ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Response Rate ◽  
Early Stage ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Refractory Multiple Myeloma ◽  
Prior Therapy ◽  
First Relapse

8594 Background: The benefit of initiating lenalidomide plus dexamethasone at first relapsed was evaluated in this subset analysis from phase III studies in patients with relapsed or refractory multiple myeloma (MM). Methods: Patients from the randomized, multicenter clinical trials MM-009 and MM-010 who had received at least 1 prior treatment and were not resistant to dexamethasone were treated with lenalidomide (25 mg daily for 21 days of every 28 day cycle) plus dexamethasone (40 mg on days 1–4, 9–12, and 17–20 every 28 days for 4 months, then 40 mg on days 1–4 every cycle thereafter until disease progression or intolerance), or dexamethasone (same dose and schedule) plus placebo. Baseline characteristics such as age, sex, ECOG score, and baseline β2-microglobulin levels between the 2 patient groups were similar, however, median time from diagnosis and prior therapy were statistically different. Results: Multivariate analysis showed that more prior therapies is associated with shorter time-to-progression (TTP). Patients who received 1 prior therapy demonstrated a significant improvement in outcomes such as TTP, progression-free survival (PFS), overall response rate (ORR), complete response/very good partial response rate (CR/VGPR), median duration of treatment and overall survival (OS) after first relapse compared with those who received ≥ 2 prior therapies ( Table ). Toxicity, rate of dose reduction, or treatment discontinuation in the cohort with 1 prior therapy did not increase, despite longer treatment. Conclusions: When used at first relapse compared with salvage therapy, lenalidomide plus dexamethasone treatment resulted in significantly prolonged TTP, PFS, and OS, and an improved quality of response. Lenalidomide plus dexamethasone should be considered at an early stage of therapy for patients with MM. [Table: see text] [Table: see text]

Bortezomib Consolidation Following Upfront ASCT for Multiple Myeloma Deepens Disease Response and MRD-Negative Rate without Compromising Response to Subsequent Bortezomib Salvage: Results of a Phase II Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4508-4508 ◽  
Author(s):  
Oliver C Cohen ◽  
Neil Rabin ◽  
Nicholas Counsell ◽  
Roger G Owen ◽  
Bilyana Popova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Progression Free Survival ◽  
Patient Choice ◽  
High Dose ◽  
Cell Transplant ◽  
Second Line ◽  
Disease Response

Abstract Background: Consolidation after high dose therapy and autologous stem cell transplant (ASCT) for multiple myeloma (MM) can improve response depth and prolong progression free survival (PFS), but it is important to ensure good quality of life (QoL) and responsiveness to further salvage therapy. We conducted a single-arm Phase II weekly bortezomib consolidation trial (BCT) to assess outcomes in MM patients receiving upfront ASCT. Methods: Bortezomib-na•ve patients with at least stable disease at 3-4 months post-high dose melphalan 200mg/m2 with ASCT received up to 8 cycles of bortezomib (1.3mg/m2 days 1,8,15,22 in a 4-week cycle), 17 intravenously (IV) and 23 subcutaneously (SC). The primary endpoint was disease response (IMWG) at 6 and 12 months post-ASCT. Other endpoints were MRD by multiparametric flow cytometry (patient 15 onwards) at 6 and 12 months post-ASCT, toxicity, PFS, overall survival, osteoblast function and Qol (EORT-QLQ-C30). Serum basic alkaline phosphatase (bALP) and ostocalcin (OC) were measured by ELISA. Results: The study recruited 40 patients between December 2009 and March 2014 at a median of 3.4 months post-ASCT. The median age was 61 years (range 43-69); 55% male; isotypes were: 22 (59%) IgG, 9 (24%) IgA, 1 (3%) IgD, 5 (14%) light chain only, 1 non-secretory and 2 unknown. Induction regimens pre-ASCT were thalidomide (33, 87%), idarubicin and dexamethasone (5, 13%). and unknown in 2. One patient was withdrawn prior to commencement (unfit for treatment) and 3 patients stopped trial treatment after 1 cycle (2 toxicity, 1 disease progression). Of 36 patients who completed >1 cycle of bortezomib, 10 stopped treatment early (5 toxicity, 4 patient choice, 1 disease progression); median number of cycles received was 8. Eleven (28%) patients experienced a total of 15 grade 3 adverse events (AE); 6 (neuropathy, 3 in IV group, 18% cf 3 in SC group, 13%), 4 (infection), 1 (fatigue), 2 (haematological), 2 other. One patient had a grade 4 infection (cycle 1, treatment discontinued) and 1 grade 4 back pain. EORTC-QLQ-C30 scores for global health status and physical, emotional and social functioning did not change significantly throughout treatment. After a median follow up of 44.4 months, 18 (45%) are alive without progression, 20 (50%) are alive with progression and 2 (5%) died after progression. BCT improved response depth in assessable patients who completed >1 cycle (n=34). Disease response at trial entry: 4 (12%) sCR/CR, 19 (56%) VGPR, 10 (29%) PR, 1(3%) SD, cf. response at 12 months post-ASCT: 7 (21%) sCR/CR, 22 (65%) VGPR, 4 (12%) PR, 1(3%) PD. Biochemical response depth improved in 12 patients. 19 patients had MRD testing at 3 (where available) or 6 months post-ASCT and again at 12 months, 10 were MRD+ at the earlier time point, of whom 4 converted to MRD- at 12 months. Of the 9 MRD- patients, all remained negative at 12 months. 15 patients (44%) had improvement in biochemical and/or MRD response at 12 months. Median PFS was 38.5 months (95%CI 29.1-47.9)(Figure). Patients who were MRD- at 12 months had median PFS of 49.2 months (95%CI 35.3-63.2) compared with 22.0 months (95%CI 21.5-22.6) in MRD+ patients (p=0.03). Of the 22 patients who relapsed, 12 received bortezomib-based salvage regimens, 5 received carfilzomib-based regimens and 5 have not started second-line therapy. Disease responses in patients receiving bortezomib salvage was 8 (67%) VGPR, 4 (33%) PR. Four patients went on to have a 2nd ASCT. In the 17 patients receiving salvage, median 2nd PFS from start of second line was 14.8 months (95%CI 8.2-18.0). At 3 months post-ASCT, levels of the osteoblast markers bALP and OC were significantly higher in CR/VGPR patients, compared to patients with PR or less (p=0.04 and 0.03, respectively). Neither marker changed significantly following BCT. Conclusions: For patients with MM, consolidation with weekly bortezomib post-ASCT is well tolerated and deepens disease response and MRD negativity without compromising the response to subsequent bortezomib-based salvage therapy. Patients who are MRD- at 12 months enjoy a median PFS of 4 years. This low intensity post-ASCT strategy deserves further study in the context of current and evolving protocols for newly diagnosed patients. Figure Figure. Disclosures Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

Lenalidomide, Bortezomib, and Dexamethasone in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Encouraging Response Rates and Tolerability with Correlation of Outcome and Adverse Cytogenetics in a Phase II Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1742-1742 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Andrzej Jakubowiak ◽  
Sagar Lonial ◽  
Noopur Raje ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Response Rate ◽  
Phase 1 ◽  
Response Rates ◽  
Disease Stage ◽  
Cell Transplant ◽  
Stage At Diagnosis ◽  
Prior Therapy

Abstract Background: Bortezomib (VELCADE®, Bz) is approved for the treatment of multiple myeloma (MM). Lenalidomide (Revlimid®, Len) plus dexamethasone (Dex) is approved for the treatment of relapsed MM pts following ≥ 1 prior therapy. In a phase 1 study, Len/Bz (maximum tolerated dose [MTD] 15 mg/1.0 mg/m2) with or without Dex (20–40 mg) was well tolerated and resulted in a response rate (CR+PR+MR) of 58% in relapsed and/or refractory MM pts. The aim of this multi-center phase 2 study was to evaluate the efficacy and safety of Len/Bz/Dex (RVD) at the phase 1 MTD. Methods: Pts with relapsed or relapsed and refractory MM with 1–3 prior lines of therapy received up to eight 21-day cycles of Bz 1.0 mg/m2 (days 1, 4, 8, 11) Len 15 mg (days 1–14) and Dex 40/20 mg (cycles 1–4/5–8) on days of/after Bz dosing. After cycle 8, pts with stable or responding disease received maintenance therapy on a 21-day cycle; Bz (days 1 and 8) and Len (days 1–14) at the dose levels tolerated at the end of cycle 8, with Dex at 10 mg (days 1, 2, 8, 9) until disease progression or unacceptable toxicity. Pts received concomitant anti-thrombotic (aspirin 81 or 325 mg/day) and anti-viral prophylaxis. Pts with Grade (G) ≥ 2 peripheral neuropathy (PNY) were excluded. Response was assessed according to modified EBMT and Uniform Criteria with toxicities assessed using NCI CTCAE v3.0. Primary end point was time to progression (TTP). Results: 64 pts have been enrolled; 38 (59%) with relapsed and 26 (41%) with relapsed and refractory MM. Median number of prior therapies was two, including Len (8%), Bz (55%), Dex (92%), thalidomide (77%), and stem cell transplant (SCT; 36%). Pts received a median of 8 cycles; 31 (48%) completed 8 cycles, 24 continue on maintenance. 4 pts proceeded to stem cell collection (median CD34+ yield of 4.58x106/kg after median of 8 cycles of therapy) and 3 pts proceeded to stem cell transplant, with the 4th pt currently undergoing salvage therapy to restore disease control. 19 pts discontinued prior to completing 8 cycles due to: progressive disease (10), toxicities (3) or other reason (2). Toxicities were manageable, consisting primarily of G1–2 myelosuppression. Attributable non-hematologic toxicities included deep vein thrombosis (two pts; attributed to Len, both pts remain on-study after antithrombotic therapy), and two episodes of atrial fibrillation (G3) prompting Dex dose reduction. G3 PNY was reported in one pt attributed to Bz and leading to treatment discontinuation despite Bz dose reduction. Dose reductions were required for: Len (13 pts); Bz (9 pts) and Dex (26 pts). One on-study death (thought to be due to fungal pneumonia) was reported during cycle 3: this was not attributed to either Bz or Len, but possibly Dex. In 63 response-evaluable pts, the overall response rate (CR/nCR+VGPR+ PR+ MR) is currently 86%, including 24% CR/nCR and 67% CR/nCR/VGPR/PR. Response rates according to baseline cytogenetics, disease stage, and prior therapies showed no significant differences according to adverse risk (Table). Similarly, analysis of evaluable pts with chromosome 13 deletion by FISH showed no significant difference in response rate compared to those without. Median DOR in responding pts is 21 weeks; range 6–72 weeks. Median TTP and overall survival have not yet been reached. Conclusions: RVD is very active and well tolerated in pts with relapsed and/or refractory MM, including pts who have received prior Len, Bz, thalidomide, and SCT. Responses appeared independent of adverse cytogenetics, advanced disease stage at diagnosis, prior treatment, and being refractory to prior therapy. Durable responses have been observed. Surrogates and correlative studies are in progress. Response rates* by baseline cytogenetics, disease stage at diagnosis, and prior treatment Cytogenetics (n= 60) ORR (≥ MR) ≥ PR ≥ VGPR CR/nCR * Response assessed by Uniform Criteria. †Abnormal cytogenetics by metaphase analysis Normal (n=38) 84% 63% 29% 18% Abnormal† (n=22) 91% 73% 41% 32% ISS disease stage (n=44) Stage l (n=15) 80% 67% 40% 33% Stage ll (n=15) 87% 67% 20% 13% Stage lll (n=14) 86% 71% 57% 36% Response to RVD according to type of prior therapy Bortezomib (n=35) 77% 57% 31% 17% Len/Thalidomide (n=54) 81% 57% 22% 15% Response by Relapsed/Refractory Relapsed (n=38) 84% 66% 34% 26% Relapsed/Refractory (n=26) 85% 65% 31% 19%

Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
D. M. Weber ◽  
C. Chen ◽  
R. Niesvizky ◽  
M. Wang ◽  
A. Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Time To Progression ◽  
Prognostic Features ◽  
High Dose Dexamethasone ◽  
Grade 3

7521 Background: Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with dexamethasone (Dex). Methods: In this phase 3, multicenter, double-blind trial, 354 patients (pts)with relapsed or refractory MM were treated with Dex 40 mg daily on days 1–4, 9–12, 17–20 every 28 days and were randomized to receive either lenalidomide (Len) 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning with cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were stratified with respect to B2M (≤ 2.5 vs. > 2.5 mg/mL), prior stem cell transplant (none vs. ≥ 1), and number of prior regimens (1 vs > 1). The treatment arms were well balanced for prognostic features. Results: The overall response rate was greater with Len-Dex than with Dex-placebo (59.4% vs. 21.1%; p < 0.001). Complete responses were achieved in 12.9% of pts treated with Len-Dex and 0.6% of pts treated with Dex-placebo. The median time to progression (TTP) for pts treated with Len-Dex was 11.1 months compared to 4.7 months for pts treated with Dex-placebo (p < 0.000001). Median overall survival was higher with Len-Dex (not reached) compared to Dex-placebo (24 months) (hazard ratio 1.76, p = .0125). Grade 3–4 neutropenia was more frequent with combination therapy than with Dex-placebo (24% vs. 3.5%), however ≥ grade 3 infections were similar in both groups. Thromboembolic events occurred in 15% of pts treated with Len-Dex and in 3.5% of pts treated with Dex-placebo. Atrial fibrillation occurred in 8 pts and CHF developed in 4 pts treated with Len-Dex. Conclusions: Considering the ease of oral administration, higher response rate, longer time to progression and overall survival benefit, the combination of lenalidomide-dexamethasone may very well represent the treatment of choice for early refractory or relapsing multiple myeloma. The relatively infrequent side effects should not detract from these improvements, but the use of prophylactic antithrombotic therapy should be considered for patients treated with the combination of lenalidomide and dexamethasone. [Table: see text]

Thalidomide and Dexamethasone Is an Effective Salvage Regimen for Myeloma Patients Relapsing after Autologous Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2396-2396
Author(s):  
Antonio Palumbo ◽  
Patrizia Falco ◽  
Maria Teresa Ambrosini ◽  
Tommaso Caravita ◽  
Pellegrino Musto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Response Rate ◽  
M Protein ◽  
Therapeutic Modality ◽  
High Dose ◽  
Salvage Regimen ◽  
Autologous Transplant ◽  
First Relapse ◽  
Protein Reduction

Abstract PURPOSE: High-dose therapy followed by autologous stem cell transplantation (AT) is the standard treatment for newly diagnosed multiple myeloma patients. Which is the best treatment option for patients relapsing after AT has not been defined. To address this issues the efficacy of Thalidomide and Dexamethasone (TD), AT and Conventional Chemotherapy (CC) was evaluated. MATERIALS AND METHODS: We retrospective analysed the outcome of 90 multiple myeloma patients, median age 61, range 34–77, who received a first salvage treatment between January 1999 and September 2003. All patients received AT at diagnosis. Relapse was defined as introduction of therapeutic modality that was different from maintenance treatment. After a median time from diagnosis of 32 months, 43 patients were treated with TD (Thalidomide 100 mg/day associated with DEX 40 mg on days 1-4 each month), after a median time from diagnosis of 29 months, 28 patients were treated at first relapse with AT (86% single MEL100, 11% double MEL100, 4% single MEL200), and after a median time from diagnosis of 32 months, 19 patients were treated with CC (32% Doxorubicin, Cyclophosphamide, Etoposide, Cisplatinum combination chemotherapy, 26% Doxorubicin containing regimens, 26% Cyclophosphamide containing regimens, 11% other therapies). Data were analysed when the median follow-up from the start of salvage TD was 30 months (range 4.5–45), from the start of salvage AT was 18 months (range 3.5–24) and from the start of salvage CC was 21 months (range 2–19.5). End points of the study were response, progression free survival (PFS) from first relapse and overall survival (OS) from first relapse and from diagnosis. RESULTS: Patients characteristics were similar among different groups. At relapse the response rate after TD was: 19% near complete remission (nCR) (absence of M-Protein detected by electrophoresis), 28% partial response (PR) (M-Protein reduction 50–99%), 35% stable disease (SD) (M-Protein reduction 0–49%) and 19% progressive disease (PD). After AT was: 11% nCR, 71% PR, 11% SD, 7% PD; and after CC was: 16% PR, 32% SD and 53% PD. Response rate was significantly lower for patients receiving salvage CC in comparison with AT and TD (p<0.001). The median PFS from relapse was 20.3 months for TD, 9 months for AT and 4.5 months for CC (p<0.001). The OS from relapse at 50 months was 58% for TD, 13% for AT and 21% for CC (p = 0.008). The median OS from diagnosis was 116.34 months for TD, 41.3 months for AT and 59.5 months for CC (p<0.001). The multivariate analysis indicates that TD, β2 microglobulin and age were the only independent risk factors associated with improved outcome. CONCLUSION: In conclusion, TD improved PFS and OS in myeloma patients relapsing after autologous transplant.

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

Combination of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in Relapsed/Refractory Multiple Myeloma: Results of a Multicenter Phase II Clinical Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 868-868 ◽  
Author(s):  
Antonio Palumbo ◽  
Patrizia Falco ◽  
Grazia Sanpaolo ◽  
Antonietta Falcone ◽  
Vincenzo Ferderico ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Drug Combination ◽  
Response Rate ◽  
Oral Prednisone ◽  
Cell Transplant ◽  
Second Line ◽  
Open Label ◽  
Grade 3

Abstract Background: In newly diagnosed multiple myeloma (MM) patients the addition of lenalidomide or thalidomide or bortezomib to the standard oral melphalan and prednisone (MP) combination significantly increased response rate and event-free survival. In advanced MM, the 4 drug combination VMPT further improves response rate. In this multicenter open label phase I/II trial the safety/efficacy profile of the 4 drug combination, lenalidomide, melphalan, prednisone and thalidomide (RMPT) was evaluated in patients with relapsed/refractory myeloma. Methods: Oral lenalidomide was administered at 10 mg/day on days 1–21, oral melphalan at 0.18 mg/kg on days 1–4, oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1–28. Each course was repeated every 28 days for a total of 6 courses. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Maintenance therapy included lenalidomide alone at 10 mg/day on days 1–21. Results: Forthy-four patients, median age 69 years (range 47–80), with relapsed or refractory MM were enrolled. Twenty-six patients received RMPT as second line of therapy, 18 as third line. Twenty patients received prior autologous transplant, 10 thalidomide-based regimen, 9 bortezomib-based regimen and 3 allogeneic stem cell transplant. After a median of 2 courses, 75.8% of patients achieved at least a partial response (PR), including 30% very good partial response (VGPR). Among patients who received RMPT as second line therapy the PR rate was 81.8%, including VGPR 36.4%.Among patients who received thalidomide 100 mg, the PR rate was 93.3% (including VGPR 46.7%) compared to 64.7% of thalidomide 50 mg. The 1-year-progressionfree survival was 48.6% and the 1-year survival from study entry was 90%. Grade 3–4 hematologic adverse events included: neutropenia (66.6%), thrombocytopenia (36.3%) and anemia (30.2%). Grade 3–4 non hematologic adverse events included: infections (21.2%), neurological toxicity (6%) and fatigue (9%). No thromboembolic events were reported. Conclusion: Initial results showed that RMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. No thromboembolic complications were reported.

scholarly journals Bortezomib in Combination with Dexamethasone, Cyclophosphamide, Etoposide, and Cisplatin (V-DCEP) for the Treatment of Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2139-2139 ◽  
Author(s):  
Kelly Valla ◽  
Jonathan L. Kaufman ◽  
Charise Gleason ◽  
Lawrence H. Boise ◽  
Leonard T Heffner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Median Time ◽  
Salvage Therapy ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
University Hospital ◽  
High Dose ◽  
Overall Response

Abstract Introduction Despite therapeutic advances in multiple myeloma, disease relapse is common. Combination therapy with dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) has been utilized as an effective salvage regimen for over a decade, and a recent study reported that DCEP provided an overall response rate of 45.1% when used as salvage therapy in patients who had previously received novel agents (Park S, et al. 2014). Aside from hematologic toxicities, DCEP is generally well-tolerated. In fact, the toxicity profile of DCEP has been compared to high dose cyclophosphamide in the setting of stem cell mobilization and is considered less toxic than the latter. Based upon the synergy noted when proteasome inhibitors are combined with genotoxic therapy, we have combined bortezomib with DCEP in a series of relapsed myeloma patients. Herein we report our experience with the addition of bortezomib to DCEP in relapsed/refractory disease. Patients and Methods We performed a retrospective evaluation of patients with relapsed/refractory multiple myeloma treated at Emory University Hospital from October 2011 until March 2014. Patients received dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) at standard doses in combination with bortezomib at either a dose of 1 mg/m2 or 1.3 mg/m2 administered on Days 1 and 4 of each cycle given every 28 days. Indications for receiving V-DCEP are either cytoreduction prior to SCT (cohort 1) or as salvage therapy (cohort 2). Results Among the 51 patients (49% male and 51% female) included in analysis, the median age at the time of diagnosis is 58 years (range 30-78) and the time of treatment with V-DCEP is 62 years (range 33-79). Among patients that received V-DCEP as cytoreduction prior to SCT, median prior lines of therapy were 1 (0-8). Among the patients that received V-DCEP as salvage therapy, median number of prior lines of therapy was 3 (1-6). ISS 3 disease was seen in 70% of patients and high risk disease in 72.5% of pts (del 17p: 31%; PCL: 19%; extramedullary disease: 33%; complex CTG: 11%) and t(4;14): 6%). Median time from diagnosis to initiation of V-DCEP therapy among cohort 1 is 18 months (0-86) and among cohort 2 is 31 months (12-105) months. Median serum creatinine before C1D1 is 1.17 (0.61-6) and serum bilirubin is 0.6 (0.1-2.8). 31% of patients needed dose reductions from our standard protocol due to organ dysfunction. 47% of patients received ≥2 cycles. The median time to next cycle is 28 days (20-46) and time to next treatment after V-DCEP is 35 days (25-451) suggesting good hematologic recovery. The overall response rate (≥PR) amongst both cohorts with V-DCEP is 47.8% (40% and 51.6% overall response for cohorts 1 and 2, respectively). Figure 1 illustrates response rates. 10 patients that presented with renal insufficiency had renal response including 2 of the 5 patients on hemodialysis. While the median PFS for cohort 1, as expected has not reached, for cohort 2, it is 8 months (95% CI 5.7-10.3). At a median follow-up of 17 months, from the time of V-DCEP initiation, median OS for cohort 2 is 10 months (95% CI 5-14.9). Median overall survival for this predominantly high risk group of patients from diagnosis in cohort 1 is 78 months (95% CI 47-108) and 49 (95% CI 17-80.7) months in cohort 2, respectively. While only 1 patient with grade 2 peripheral neuropathy (PN) received V-DCEP, change from baseline existing PN was seen in 19% of patients (no grade 3/4 events). Conclusions During this era where minimizing alkylator therapy is a consideration, certain indications exist for using V-DCEP such as cytoreduction prior to SCT or as salvage therapy serving as bridge to next line of therapy. Addition of bortezomib to DCEP is deemed safe and is an effective cytoreductive regimen in the treatment of multiple myeloma. Figure 1 Figure 1. Disclosures Gleason: Celgene: Consultancy; Novartis: Consultancy. Heffner:Amgen: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Dana Farber CI: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Idera: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Spectrum: Honoraria, Research Funding; Talon Therapeutics: Honoraria, Research Funding. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

Thalidomide and Dexamethasone as Salvage Therapy after First Relapse in Multiple Myeloma: Analysis of Long-Term Outcomes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4933-4933
Author(s):  
Elena Zamagni ◽  
Alessandro Petrucci ◽  
Patrizia Tosi ◽  
Paola Tacchetti ◽  
Lucia Pantani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Median Duration ◽  
Salvage Therapy ◽  
Low Dose ◽  
Long Term Outcomes ◽  
Prior Therapy ◽  
First Relapse ◽  
Grade Iii

Abstract Abstract 4933 Bortezomib and lenalidomide have been approved in the U.S. and Europe for the treatment of patients with advanced refractory/relapsed multiple myeloma (MM). In this setting, both these agents effected the highest activity among patients who relapsed after a single line of prior therapy. In particular, with early introduction of bortezomib at first relapse median TTP was 7 months vs 4.9 months with use of the same drug as third, or more, line of therapy; 1-year OS rates were 89% vs 73%, respectively. Similarly, reported median PFS and OS with lenalidomide and dexamethasone at first relapse were 14.1 and 42 months, respectively. Since the first report of single agent thalidomide (thal) for the treatment of MM patients who had failed multiple lines of prior therapy, including autologous stem-cell transplantation (ASCT), a large number of studies have investigated this drug further in the setting of advanced relapsed/refractory disease, most frequently combined with dexamethasone (dex).Aim of the present analysis was to evaluate the long-term outcomes of a series of 100 patients who received thal-dex as salvage therapy at first relapse after prior ASCT or conventional chemotherapy. By study design, thal was started at the dose of 100 mg/daily for two weeks and then escalated to 200 mg/daily, provided that the initial tolerance was acceptable. Otherwise, thal was continued at the initial dose until progression. Dex was given at a monthly dose of 160 mg. The first 60 patients did not receive any thromboprophylaxis, while fixed low-dose warfarin (0.25 mg/day) was added to thal-dex in the subsequent 40 patients. Median age of the patients was 62 years. Median time from start of first-line therapy to thal-dex was 34 months. Up-front therapy for MM had included ASCT, either single (30%) or double (42%), while the remaining 28 patients had previously received conventional chemotherapy. 59% of the patients were treated with a fixed thal dose of 100 mg/daily, while in the remaining 41% of patients the dose was increased up to 200 mg/daily. Overall, median duration of thal-dex therapy was 14 months. 65% of the patients stayed on treatment beyond the achievement of the best response or plateau phase; median duration of thal in these patients was 22 months (range 1-79). The most frequent adverse events were constipation (42%, grade III 8%), peripheral neuropathy (58%, grade III 5%), bradycardia (20%, grade III 0%) and skin rash (11%, grade III 1%). Venous thromboembolism was recorded in 7 patients (3 not receiving any thromboprophylaxis), at a median of 8 months (range 3-11) from the start of thal-dex therapy. The frequency of grade III neuropathy was significantly higher in patients receiving thal 200 mg/daily in comparison with those treated with 100 mg/daily (8.5% vs 1%, respectively, P = 0.01). Discontinuation of thal due to toxicity was recorded in 8 patients after a median of 12 months. On an intention to treat basis, 46% of patients achieved at least a partial response at a median time of 3 months from the start of thal-dex treatment; the response rate was not significantly different between patients receiving thal 100 mg/daily and those treated with 200 mg/daily. The median duration of response (DOR) was 28 months, while the median time to next therapy was 15.5 months. With a median follow up of 25 months, median OS, TTP and PFS were 43, 22 and 21 months, respectively. TTP and PFS were significantly longer for patients responding to thal-dex therapy (TTP: 34 months vs 15 months for nonresponders, P = 0.005; PFS: 28 months vs 12 months for nonresponders, P = 0.001, respectively). Median survival after relapse from thal-dex therapy was 26 months. In conclusion, low-dose thal-dex was an effective treatment of MM at first relapse. Although cross-trial comparisons are not adequate, results herein reported with thal-dex in terms of DOR, OS and EFS were similar to those previously seen with other novel agents when used in the same setting of patients. Low-dose thal-dex was generally well tolerated, as reflected by the long stay on treatment in the absence of disease progression (median: 25 months) and a low discontinuation rate due to toxicity (8%). Disclosures Off Label Use: In this study thalidomide was administered as salvage therapy for first relapse in multiple myeloma patients.

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