Pomalidomide, bortezomib, and dexamethasone (PVd) in lenalidomide (LEN)-pretreated relapsed refractory multiple myeloma: Subanalysis of patients with renal impairment in OPTIMISMM.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20562-e20562
Author(s):  
Fredrik Schjesvold ◽  
Meletios A. Dimopoulos ◽  
Meral Beksac ◽  
Albert Oriol ◽  
Jindriska Lindsay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Depth Of Response ◽  
Common Grade ◽  
First Relapse ◽  
Grade 3 ◽  
Line Of Therapy

e20562 Background: Upfront LEN until disease progression is a standard treatment (Tx) in multiple myeloma (MM). Data are limited on optimal Tx after first-line LEN, especially in LEN-refractory patients (pts), a growing population. In OPTIMISMM (phase 3, NCT01734928), PVd significantly improved median PFS at first relapse in relapsed refractory MM (RRMM) pts, of whom 100% were LEN pretreated and 57% were LEN refractory (median, 20.7 vs 11.6 mos; HR = 0.54 [95% CI, 0.36-0.82]; P = .0027) vs Vd (Richardson, 2019). Pd has shown efficacy and safety in RRMM pts with moderate or severe renal impairment (RI), including those on dialysis (Dimopoulos, 2018). However, outcomes with second-line PVd in RRMM pts with RI have not been assessed. Here we report efficacy and safety of PVd vs Vd at first relapse by renal status (CrCl < 60 vs ≥ 60 mL/min). Methods: Pts received PVd or Vd (1:1) in 21-day (D) cycles (C); POM 4 mg/D on D1-14 (PVd arm only); BORT 1.3 mg/m2 on D1, 4, 8, 11 of C1-8 and on D1, 8 of C9+; and DEX 20 mg/D (10 mg/D for pts aged > 75 yrs) on days of and after BORT. Pts on dialysis were excluded. Results: Of 559 pts enrolled, 226 (40%) had 1 prior line of therapy; of whom 28% had CrCl < 60 mL/min and 4% had severe RI (CrCl < 30 mL/min). In pts with CrCl < 60 mL/min (PVd vs Vd), median age was 74 vs 73 yrs. In pts with CrCl ≥ 60 mL/min (PVd vs Vd), median age was 62 vs 64 yrs. A higher proportion of pts with baseline CrCl < 60 (23% vs 43%) than ≥ 60 mL/min (7% vs 8%) had ISS stage III at study entry. Data cutoff was Oct 26, 2017. Median PFS was improved with PVd in both renal groups (Table). ORR significantly improved regardless of renal status. Depth of response also improved with PVd vs Vd; ≥ VGPR occurred in 54% vs 21% in the CrCl < 60 mL/min group and 64% vs 23% in the CrCl ≥ 60 mL/min group. Myelosuppression was the most common grade 3/4 TEAE (Table). Conclusions: Second-line PVd led to improved vs Vd in pts with RRMM and RI; however, the PFS difference was not statistically significant. Safety was consistent for PVd with no new signals in pts with RI. These findings further support the earlier use of POM-based Tx in RRMM pts, including those with mild to moderate RI. Clinical trial information: NCT01734928. [Table: see text]

Daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (RRMM): Efficacy and safety update (CASTOR).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8036-8036 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Katja C. Weisel ◽  
Maria-Victoria Mateos ◽  
Vania Hungria ◽  
Markus Munder ◽  
...  
Keyword(s):  
Residual Disease ◽  
Randomized Study ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Depth Of Response ◽  
Common Grade ◽  
Previously Treated ◽  
Grade 3 ◽  
Line Of Therapy

8036 Background: Daratumumab (D), a human, CD38-targeting mAb, is well tolerated and induces deep and durable responses in patients (pts) with RRMM. We provide an update of CASTOR (NCT02136134), a multicenter, phase 3, randomized study of DVd vs Vd in RRMM. Methods: All pts received ≥1 prior line of therapy (LOT) and were administered 8 cycles (Q3W) of Vd (1.3 mg/m2 SC bortezomib on days 1, 4, 8, and 11; 20 mg PO/IV dexamethasone on days 1-2, 4-5, 8-9, and 11-12) ± D (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks for Cycles 4-8, then every 4 weeks until progression). Bortezomib-refractory pts were ineligible. Minimal residual disease (MRD) was assessed upon suspected CR and at 6 and 12 months following the first dose at sensitivities of 10–4, 10–5, and 10–6using the ClonoSEQ assay (Adaptive Biotechnologies, Seattle, WA). Results: Pts received a median (range) of 2 (1-10) prior LOTs. 66% were previously treated with bortezomib and 21% were refractory to lenalidomide in their last prior LOT. After a median follow-up of 13.0 months, PFS was significantly prolonged with DVd vs Vd (median: not reached vs 7.1 months; HR, 0.33; 95% CI, 0.26-0.43; P< 0.0001). This PFS benefit was seen regardless of number of prior LOTs received, with greatest benefit observed in 1 prior line pts (median: not reached vs 7.9 months; HR, 0.22; 95% CI, 0.14-0.34; P< 0.0001). ORR was also significantly higher for DVd vs Vd (84% vs 63%), along with ≥VGPR (62% vs 29%) and ≥CR (26% vs 10%; P< 0.0001 for all). MRD-negative rates were ≥4-fold higher at all three sensitivity thresholds with DVd vs Vd (10% vs 2% at 10–5 threshold). Pts who achieved MRD negativity demonstrated prolonged PFS compared with MRD-positive pts. 37 (15%) and 58 (24%) deaths were observed in DVd vs Vd, respectively, and follow up is ongoing. The most common grade 3/4 TEAE was thrombocytopenia (45% vs 33%). Updated efficacy and safety data will be presented. Conclusions: DVd provided significant benefits with respect to PFS, ORR, depth of response, and MRD-negative rate vs Vd. No new safety signals were reported. These data continue to support the use of DVd in RRMM pts and indicate that pts with 1 prior LOT will derive the most benefit. Clinical trial information: NCT02136134.

Bortezomib-Dexamethasone Alone or Plus Cyclophosphamide or Lenalidomide As Second-Line Treatment for Patients with Multiple Myeloma: Final Results From a Phase 2 Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1861-1861
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Meral Beksac ◽  
Lotfi Benboubker ◽  
Huw Roddie ◽  
Nathalie Allietta ◽  
...  
Keyword(s):  
Response Rate ◽  
Stage Migration ◽  
Second Line ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Line Of Therapy

Abstract Abstract 1861 Background: Bortezomib plus dexamethasone (VD) has been shown to be effective and well tolerated in patients (pts) with multiple myeloma (MM) as frontline induction therapy and in relapsed pts; however, no studies have prospectively assessed VD as second-line therapy. The addition to VD of cyclophosphamide (VDC) or lenalidomide (VDR) may improve efficacy, but with increased toxicities. This phase 2 study evaluated the efficacy and safety of VD, with the addition of C or R for pts with stable disease (SD) after 4 cycles, in pts with relapsed or refractory MM following 1 prior line of therapy. This is the first prospective study of VD as second-line therapy for MM. Methods: Bortezomib-naïve pts aged ≥18 years with measurable MM and no grade ≥2 peripheral neuropathy (PN) who had relapsed/progressed after 1 previous line of therapy received four 21-day cycles of VD (bortezomib 1.3 mg/m2, days 1, 4, 8, 11; Dex 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12). Pts achieving at least partial response (PR) then received a further 4 cycles of VD. Pts with SD were randomized to a further 4 cycles of VD, or 4 cycles of VDC (VD + C 500 mg, days 1, 8, 15), or VDR (VD + R 10 mg, days 1–14) for Cycles 5–8. Pts with progressive disease (PD) discontinued treatment. The primary end point was response rate; secondary end points included time to response, duration of response (DOR), safety, and improvement in renal function (defined by the Cockcroft-Gault glomerular function rate [GFR], assessed prior to treatment on day 1, Cycles 1–5). Results: A total of 189 pts were enrolled; 26 did not receive therapy and were excluded from the safety/ITT population (N=163). Median age was 63 years (range 34–86), 53% were male, 20% had KPS ≤70; median time from prior therapy was 13.9 months. In the ITT population, 52% of pts (84/163) experienced an OR by Cycle 4 as validated by IDMC. Discontinuations were due to toxicity (N=10), death, PD, and other reasons (6 each). Of 135 remaining pts who started Cycle 4 treatment, 120 pts had a response assessment at Cycle 4; according to investigators, 82% of these pts experienced an overall response (OR) and 2.5% had PD; median time to first and best response was 49 and 85 days, respectively. Nineteen pts had SD and were randomized: 7 to VD, 8 to VDC (1 did not continue treatment), 4 to VDR. Only 11 pts received a third drug, C or R, in addition to VD. Due to the high response rate for the first four cycles, the second randomization arm was not completed. 47% (77/163) had continued treatment up to Cycle 8. Based on IDMC response validation as of June 2011, 122 patients had a Best Confirmed Response: 75% OR, 20% SD, and 4% PD. GFR results at Cycle 8 are shown in the Table. In pts who had baseline and on-study assessments, median GFR was 62.2 mL/min at baseline and increased after Cycles 1, 2, 3, 4, 5, 6, 7, and up to Cycle 8 by 4.5, 5.7, 9.4, 8.7, 6.0, 9.6, 8.9, and 5.5 mL/min, respectively. Of the 26 pts with stage migration from baseline GFR to best GFR at Cycle 4, 12 had a renal response (MR renal). Of the 24 pts with baseline GFR <50 ml/min and renal response with stage migration from baseline GFR to best GFR at Cycle 8, 13 had CR renal, 11 had MR renal. Grade 3/4 adverse events (AEs) occurred in 64% of pts; the most common were thrombocytopenia (17%), anemia (10%), and constipation (6%). 40% of pts had serious AEs, and 46%/29%/12% had AEs resulting in dose reductions/discontinuation/death. Overall rates of sensory PN, polyneuropathy, PN (neuropathy peripheral), and motor PN in Cycles 1–8 were 20%, 18%, 13%,and 1% respectively, including 5%, 5%, 4%, and 1% grade 3/4, respectively; 55% of PN events were reversible, with resolution in 43%. Conclusions: This is the first prospective trial which assessed VD as second-line treatment in MM. VD is effective and well tolerated with less than 10% of pts receiving subsequent C or R added to VD. Overall renal function was shown to improve with treatment. PN was manageable with good reversal rates. VD represents a feasible, active treatment option for pts with relapsed MM. Final efficacy and safety data will be presented. Disclosures: Dimopoulos: Ortho Biotech: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc: Consultancy, Honoraria. Beksac:Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Allietta:Covance for Janssen-Cilag: Employment. Broer:Janssen-Cilag: Employment. Couturier:Janssen-Cilag: Employment. Angermund:Janssen-Cilag: Employment. Facon:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Efficacy and Safety of Melphalan 140mg/m2 Conditioned Autologous Stem Cell Transplantation in Elderly Pre-Dialysis and Dialysis Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5822-5822
Author(s):  
Hatem Ali ◽  
Baharani Jyoti ◽  
Shankaranarayana Paneesha ◽  
Richard Lovell ◽  
Alex George Kanellopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Renal Impairment ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Severe Renal Impairment ◽  
Efficacy And Safety ◽  
Dialysis Patients ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Information is currently available for the efficacy and safety of autologous stem cell transplantation (ASCT) conditioned with melphalan in multiple myeloma patients with mild to moderate chronic kidney disease. However, little information is available on ASCT in patients with severe renal impairment or those on dialysis with multiple myeloma. This population is usually not considered for ASCT due to a high risk of mortality. One retrospective study provides data on ASCT conditioned mainly with 200mg/m2 melphalan with high treatment related mortality (TRM) at 15%. Here we present safety and efficacy data on dose reduced melphalan (140/m2) conditioned ASCT in patients with severe renal impairment or haemodialysis at the time of transplant with a TRM of 0%. Patients and methods: We identified and report on 10 ASCT procedures carried out on 9 (7 males and 2 females) myeloma patients with a glomerular filtration rate (eGFR) of 35 ml/min/1.73m2 or less between 2006 and 2016. Median age was 58(51-74) years. Five patients were on haemodialysis at diagnosis and 4 went into ASCT while on haemodialysis. Six patients had light chain multiple myeloma. Initial therapy was bortezomib based in 6 patients, with 4 receiving thalidomide and 1 received both thalidomide and bortezomib pre ASCT. Most patients were mobilised with G-CSF alone and only 1 received cyclophosphamide and G-CSF. ASCT was conditioned in all cases with 140mg/m2of Melphalan. Patients on hemofiltration were supported during ASCT as per institutional guidelines. We collected data on response, stem cell collection, engraftment, progression free survival (PFS), overall survival (OS) and treatment related mortality (TRM). Results: Median follow up for the whole group was 24 (6-114) months. Pre ASCT 6 patients were in VGPR and 3 in PR. The median cell dose collected was 6.92×10 6 CD34 cells/kg (range 3.06-8.27). The median time to neutrophil engraftment (absolute neutrophil count>0.5×109/L) and platelet engraftment (>20×109/L) was at day 13 and 15 respectively. The TRM at day+100 was 0%. Post ASCT best responses were as follows-7 patients were in VGPR; 1 in PR and 1 progressed. The median PFS was 24months and median OS was 27 months. At the time of data collection only one person had died. The cause of death was disease progression with refractory disease. One patient became free of haemodialysis pre ASCT, one after ASCT and 1 more dropped frequency of dialysis sessions from 3 to 2 per week. Discussion: Autologous stem cell transplant using low dose Melphalan (140mg/m2) as consolidation post a bortezomib based induction therapy is an effective and safe treatment option for the pre-dialysis and dialysis patients with multiple myeloma. In our hands the TRM is extremely low suggesting the lower dose to be more appropriate than melphalan at 200mg/m2. It provides good PFS and in some cases freedom from haemodialysis. Further prospective trials are needed to confirm these findings. Disclosures Paneesha: Abvie: Honoraria. Kishore:celgene: Other: travel grant.

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.

Safety and efficacy of daratumumab-based regimens in elderly (≥75 y) patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Subgroup analysis of POLLUX and CASTOR.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8033-8033 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Andrew Spencer ◽  
Ajay K. Nooka ◽  
Ludek Pour ◽  
Katja C. Weisel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Phase 3 ◽  
Safety And Efficacy ◽  
Common Grade ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Experienced Grade ◽  
Clinical Trial Information

8033 Background: Daratumumab (D) plus lenalidomide and dexamethasone (Rd; POLLUX) or with bortezomib and dexamethasone (Vd; CASTOR) demonstrated prolonged PFS and tolerability compared with Rd and Vd alone, respectively, in RRMM pts. We examined the safety and efficacy profiles of DRd and DVd in elderly (≥75 y) pts from these phase 3 studies. Methods: Pts with ≥1 prior line of therapy were enrolled. All pts in POLLUX were treated until progression; CASTOR pts received 8 cycles of Vd ± daratumumab. Different D (16 mg/kg) dosing schedules were used in POLLUX (qw for cycles 1-2, q2w for cycles 3-6, and q4w thereafter) and CASTOR (qw in Cycles 1-3, q3w for Cycles 4-8, and q4w thereafter). Elderly pts received a reduced dexamethasone dose (20 mg once weekly). Results: In POLLUX, 29/286 (DRd) and 35/283 (Rd) were ≥75 y, with 86% and 91% having ECOG status ≤1, respectively. With 17.3 months of median follow up, 10% in DRd and 11% in Rd discontinued due to treatment-emergent adverse events (TEAEs). Common (>10%) grade 3/4 TEAEs for DRd included neutropenia and hypokalemia (Table). Twelve (41%) DRd pts experienced infusion-related reactions (IRR) and 4 (14%) experienced grade 3/4 IRR; none discontinued due to IRR. Median PFS was not reached (NR) in DRd vs 11.4 months in Rd (HR 0.19; 95% CI, 0.06-0.55; P=0.0007), and ≥CR % was significantly higher with DRd vs Rd (52% vs 9%; P=0.0002). In CASTOR, 23/251 (DVd) and 35/247 (Vd) were ≥75 y, with 100% and 94% having ECOG status ≤1, respectively. With 13.0 months of median follow up, rates of discontinuation due to TEAEs were similar (15% vs 20%). Thrombocytopenia, fatigue, and pneumonia were common grade 3/4 TEAEs for DVd (Table). Thirteen (65%) pts reported IRR (10% grade 3/4) and no pts discontinued due to IRR. Median PFS was NR in DVd vs 8.1 months in Vd (HR 0.27; 95% CI, 0.12-0.61; P=0.0007), and significantly higher ≥CR % was observed in DVd vs Vd (25% vs 3%; P=0.0154). Conclusions: The safety and efficacy profiles in elderly pts were generally comparable with the overall population in each study. Clinical trial information: NCT02136134 and NCT02076009. [Table: see text]

The efficacy and safety of lenalidomide in multiple myeloma with severe renal impairment

2015 ◽  
Vol 15 ◽  
pp. e310
Author(s):  
K.S. Jung ◽  
H.-N. Song ◽  
K.H. Yoo ◽  
J.Y. Lee ◽  
S.H. Lim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Efficacy And Safety

scholarly journals Efficacy and Safety of Daratumumab Based Regimens for Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3292-3292
Author(s):  
Muhammad Abu Zar ◽  
Ahmad Kamal ◽  
Ali Younas Khan ◽  
Saad Ullah Malik ◽  
Mustafa Nadeem Malik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
Cochrane Library ◽  
Extensive Literature ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Line Of Therapy

Abstract Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 that has been approved for the treatment of multiple myeloma (MM). We performed a meta-analysis of trials with daratumumab to find its efficacy and safety. Materials and Methods: Extensive literature search of Medline, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov on 5/07/2018 identified a total of 1596 articles. Fourteen articles (n = 1439) met the inclusion criteria, eleven in the relapsed and refractory multiple myeloma (RRMM) and three in the newly diagnosed multiple myeloma (NDMM) group (Table 1). A meta-analysis was performed using STATA version 15 and inter study heterogeneity was calculated using I² statistic. Results: The overall response rate (ORR) was 69% (95% CI: 51-84%) and very good partial response or better (≥VGPR) was 40% (95% CI: 22-60%) in RRMM patients. In a subgroup analysis with three, two and single drug regimen, ORR was 85% (95% CI: 77-92%), 30% (95% CI: 21-40%) and 31% (95% CI: 24-39%) respectively in RRMM patients. The hazard ratio (HR) for progression free survival (PFS) with daratumumab based regimens was 0.35 (95% CI: 0.26-0.45) as compared to non-daratumumab based regimens in two randomized controlled trials (RCTs). The most effective regimen, in terms of PFS for RRMM patients with a median of a single previous line of therapy was daratumumab with lenalidomide with dexamethasone (24-months PFS rate: 68%) in the POLLUX trial (Dimopoulos et al., 2017). The ORR was 97% (95% CI: 92-100%) and ≥VGPR rate was 64% (95% CI: 44-83%) in NDMM patients (Figure 1). In the only available RCT for NDMM patients, the HR for PFS was 0.50 (95% CI: 0.38-0.65) (Mateos et al., 2017). Incidence of neutropenia was 30% (95% CI: 16-46%) and thrombocytopenia was 25% (95% CI: 15-37%). While the incidence of anemia was 17% (95% CI: 13-21%). Incidence of ≥ grade 3 non-hematologic treatment emergent adverse effects (TEAEs) were as follows: pneumonia (11.3-12%), hypertension (8-12%) and fatigue (4-12.5%). In daratumumab and non-daratumumab based regimens ≥ grade 3 infusions related reactions occurred in 5% of the patients. In the three RCTs, these hematologic (≥ grade 3) TEAEs were comparable as neutropenia occurred in 36.86% vs 29.57%, thrombocytopenia in 30% vs 29% and anemia in 16.67% vs 19% respectively. Patients on daratumumab based regimens who discontinued treatment due to TEAEs were 8.56% vs 9.93% on non-daratumumab based regimens in the three RCTs which shows that most of the treatment discontinuations was due to other drugs in the regimen. Conclusion: Our results suggest that daratumumab containing regimen is more effective than non-daratumumab based regimens for RRMM and NDMM patients. Three drug daratumumab based regimens are more effective when compared to two drug or daratumumab monotherapy regimens. The safety profile of daratumumab is favorable, which makes it an extremely useful drug. Despite limited data in NDMM patients, daratumumab based regimens appear to be highly effective. Further prospective randomized trials are needed to compare various daratumumab based regimens. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real Life, Retrospective Analysis of Bortezomib Re-Use As Second Treatment for Relapsed Multiple Myeloma Patients Previously Exposed to Bortezomib-Based Therapies As First Line: The Rebound Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4494-4494
Author(s):  
Pellegrino Musto ◽  
Vittorio Simeon ◽  
Nicola Cascavilla ◽  
Antonietta Falcone ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Salvage Therapy ◽  
Research Funding ◽  
Real Life ◽  
Advisory Board ◽  
Second Line ◽  
First Line ◽  
First Relapse ◽  
Grade 3

Abstract Background: Several trials and analysis have explored the efficacy of bortezomib re-use in relapsed patients with multiple myeloma (MM), notably in those who have experienced good response and late relapse after the end of frontline treatments including the same drug. However, very few specific evidences on bortezomib re-challenge at first relapse are available. Patients and methods: This observational, retrospective study enrolled 135 MM patients treated from January 2002 to May 2015 in 12 Italian centres with bortezomib-based regimens as first line therapy (both in daily practice or clinical trials) and who had received again a salvage treatment containing bortezomib at first relapse, according to current clinical practice and/or guidelines recommendations. Results: Median age was 61 years (range 28-95) and 60% of patients were males. At diagnosis, ISS was 30% stage I, 30% stage II and 40% stage III; r-ISS (available in 45 cases) was 25% stage I, 44% stage II and 31% stage III. Two patients presented as primary plasma cell leukemia (PCL). First line induction treatments included VD (27%), VTD (25%), VMP (23%), PAD (10%), and further combinations of bortezomib with cyclophosphamide (11%) or other drugs (4%). Eighty-two percent of patients received a twice-week schedule and 18% once-a-week administration of bortezomib, which was initially given i.v. in 71% and s.c. in 29% of patients, respectively. Seventy-five patients (56%) underwent single (72%) or double (28%) autologous stem cell transplantation (AuSCT) as part of their frontline therapy. Consolidation or maintenance with borteomib were performed in 17 and 4 patients, respectively. As per inclusion criteria, all patients achieved PR or better response (according to IMWG criteria), including at least VGPR in 36%, CR in 20% and sCR in 1% of cases. Median duration of PFS1 was 33 months (95% CI 28-36), while median treatment free-interval (TFI) was 23 months (95% CI 22-28). Median PFS1 was 35 months (95% CI 31-43) and 27 months (95% CI 20-33) for patients undergoing or not AuSCT, respectively (p n.s.). At first relapse (clinical 65%, only biochemical 35%), anemia, neutropenia and thrombocytopenia were present in 42%, 5% and 9% of patients, respectively. Median bone marrow plasma cell infiltration was 40% (range 2-99). Bone lesions were present in 74%, hypercalcemia in 7%, high LDH values in 15% of patients. Serum beta2-microglobulin levels were increased in 48%, while albumin was decreased in 17%. Renal failure was observed in 14%, with a median value of serum creatinine of 2.2 mg/dl (range 1.4-7). PCL occurred in 3 patients. Second line regimens included VD (44%), VCD (11%), PAD (9%), VTD (7%), BVD (7%), VMP (7%), VRD (4%), VRCD (2%), or other combinations (9%). Six patients had maintenance therapy with bortezomib. Twenty-one patients (16%) received AuSCT as part of their salvage therapy, while 4 patients (3%) underwent allogeneic transplantation (AlloSCT) and 5 (4%) a tandem sequence of AuSCT followed by AlloSCT. Seventy-four percent of patients received bortezomib once-a-week, 26% twice-weekly, 35% i.v. and 65% s.c. A total of 782 cycles (median 6, range 1-13) were given. Grade 3-4 hematological and non-hematological toxicities occurred in 27% and 10% of patients, respectively. No patient reported grade 3-4 neuropathy. Bortezomib dose reductions were needed in 12%. SPM occurred in 1 patient. Overall response rate was 70%, with 24% at least VGPR and 7% CR (sCR/nCR 1.5%). Improvement of renal failure (13 cases) was complete in 4 and partial in 6 patients. Bone disease improved in 31% of patients with osteolytic lesions. Median duration of second PFS was 19 months (95% CI 13-23), while that of second TFI was 14 months (95% CI 8-17). Median PFS2 was 56 months (95% CI 50-70); it was 60 months (95% CI 54-78) for patients who underwent AuSCT and 50 months (95% CI 45-68) for those who did not (p n.s.). Median OS was 94 months (95% CI 80-121) for the entire cohort, 94 months (95% CI 75-107) for patients undergoing AuSCT, and 86 months (95% CI 76-92) for those who did not receive AuSCT. After a median follow up of 56 months, 85 patients (63%) are alive, with 41 of them in response after second line therapies containing bortezomib. Conclusions: This real-life survey indicates that re-treatments including bortezomib as first salvage therapy should be considered for selected MM patients achieving prolonged response after initial exposure to first line, bortezomib-based regimens. Disclosures Musto: Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cascavilla:Janssen-Cilag: Honoraria. Falcone:Janssen-Cilag: Honoraria. Petrucci:Janssen-Cilag: Honoraria. Di Raimondo:Janssen-Cilag: Honoraria. Ria:Binding Site: Speakers Bureau; BMS: Speakers Bureau; BMS: Speakers Bureau; Italfarmaco: Consultancy, Speakers Bureau; Janssen-Cilag: Other: Advisory Board, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau. Mastrullo:Janssen-Cilag: Honoraria. D'Arena:Janssen-Cilag: Honoraria. Bringhen:Janssen-Cilag: Honoraria; Celgene: Honoraria; BMS: Honoraria; Amgen: Other: ADVISORY BOARD; Mundipharma: Other: ADVISORY BOARD; Karyopharm: Other: ADVISORY BOARD. Di Renzo:Janssen-Cilag: Honoraria. Caravita:Janssen-Cilag: Honoraria. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Corso:Janssen-Cilag: Honoraria.

LocoMMotion: A prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma (RRMM) receiving ≥3 prior lines of therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8041-8041
Author(s):  
Maria-Victoria Mateos ◽  
Katja Weisel ◽  
Valerio De Stefano ◽  
Aurore Perrot ◽  
Niels W.C.J. van de Donk ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real Life ◽  
Primary Objective ◽  
Standards Of Care ◽  
Efficacy And Safety ◽  
Standard Drug ◽  
The Us ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Ecog Ps

8041 Background: Multiple myeloma (MM) remains incurable despite advances in medical treatment that have improved survival. Even with these improvements, most patients with MM eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs), and others. There are currently no prospective data on real-world standard-of-care (SOC) in patients who progress after PIs, IMiDs, and anti-CD38 mAbs. Here, we present interim results from LocoMMotion (NCT04035226), the first prospective efficacy and safety study of real-life SOC in patients with RRMM. Methods: Eligible patients (aged ≥18 years [y]) with a diagnosis of MM were enrolled between August 2019 and October 2020 from 75 sites across 9 European countries and the US. Patients were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD, had measurable disease at screening, received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy, and had an ECOG PS score of 0 or 1. Responses were assessed per International Myeloma Working Group response criteria. A Response Review Committee assessed the overall response rate (ORR, primary objective) of real-life current SOC. Secondary objectives of the study included additional efficacy and safety evaluation of real-life SOC. Results: The data cut-off was November 4, 2020 for the first interim analysis of 225 patients with a median follow-up of 3.7 months (range: 0–12.7), 22 (9.8%) patients were from the US and 203 (90.2%) were from Europe. Median age was 68 y (range: 41–89), 124 (55.1%) were male, 162 (72.0%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.0 y (range: 0.3–22.8). Patients had received a median of 4.0 (range: 2–13) prior lines of therapy; all patients were triple-class exposed, 166 (73.8%) were triple-class refractory, and 208 (92.4%) were refractory to last line of therapy. The ORR with real-life SOC salvage therapy was 20.1% (95% CI: 15.0–26.0) in the response-evaluable population (n = 219). Treatment-emergent adverse events (TEAEs) were reported in 148 (65.8%) patients, 95 (42.2%) were grade ≥3. The most common grade ≥3 TEAEs were anemia, thrombocytopenia, and neutropenia. Fifteen deaths (6.7%) occurred due to TEAEs during the study. Treatment is ongoing in 121 (53.8%) patients. Conclusions: The interim results of this first, prospective study of real-life SOC treatment in heavily pretreated, triple-class exposed patients with RRMM demonstrate that patients continue to progress after multiple lines of therapy and have poor outcomes. Therefore, there is a need for new treatments with novel mechanisms of action for this patient population. Clinical trial information: NCT04035226.

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