scholarly journals Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma

Blood ◽  
2020 ◽  
Vol 136 (22) ◽  
pp. 2513-2523 ◽  
Author(s):  
Jagoda K. Jasielec ◽  
Tadeusz Kubicki ◽  
Noopur Raje ◽  
Ravi Vij ◽  
Donna Reece ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Cardiac Events ◽  
End Point ◽  
Depth Of Response ◽  
Grade 3

Abstract In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point was met, with an sCR rate of 60% after 8 cycles. Depth of response improved over time. On intent-to-treat (ITT), the sCR rate reached 76%. The rate of minimal residual disease (MRD) negativity using modified ITT was 70% according to next-generation sequencing (<10−5 sensitivity). After median follow-up of 56 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 72% and 84% for ITT, 85% and 91% for MRD-negative patients, and 57% and 72% for patients with high-risk cytogenetics. For high-risk patients who were MRD negative, 5-year rates were 77% and 81%. Grade 3 to 4 adverse events included neutropenia (34%), lymphopenia (32%), infection (22%), and cardiac events (3%). There was no grade 3 to 4 peripheral neuropathy. Patients with NDMM treated with KRd with ASCT achieved high rates of sCR and MRD-negative disease at the end of KRd consolidation. Extended KRd maintenance after consolidation contributed to deepening of responses and likely to prolonged PFS and OS. Safety and tolerability were manageable. This trial was registered at www.clinicaltrials.gov as #NCT01816971.

scholarly journals Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial

Blood ◽  
2020 ◽  
Vol 136 (8) ◽  
pp. 936-945 ◽  
Author(s):  
Peter M. Voorhees ◽  
Jonathan L. Kaufman ◽  
Jacob Laubach ◽  
Douglas W. Sborov ◽  
Brandi Reeves ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Depth Of Response ◽  
Grade 3 ◽  
Intent To Treat

Abstract Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N = 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P = .068) and met the prespecified 1-sided α of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P = .0177), as did minimal residual disease (MRD) negativity (10−5 threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P < .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD34+ cell yield was 8.2 × 106/kg for D-RVd and 9.4 × 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT02874742.

scholarly journals Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma

Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1953-1963 ◽  
Author(s):  
Thierry Facon ◽  
Jae Hoon Lee ◽  
Philippe Moreau ◽  
Ruben Niesvizky ◽  
Meletios Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intention To Treat ◽  
Significant Difference ◽  
Grade 3

Abstract The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease–negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.

Isatuximab plus carfilzomib and dexamethasone in patients with relapsed multiple myeloma according to prior lines of treatment and refractory status: IKEMA subgroup analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8034-8034
Author(s):  
Roman Hajek ◽  
Philippe Moreau ◽  
Bradley Augustson ◽  
Nelson Castro ◽  
Tomas Pika ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Complete Response ◽  
Depth Of Response ◽  
Refractory Status ◽  
New Treatment ◽  
Grade 3 ◽  
D 20

8034 Background: Patients (pts) with multiple myeloma (MM) often relapse and become refractory to successive lines of therapy, warranting better treatment options. The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in pts with relapsed MM (RMM) (HR 0.53; 99% CI 0.32–0.89; P= 0.0007). We evaluated the efficacy and/or safety of Isa-Kd by number of prior lines of therapy (1 vs > 1) and refractoriness to lenalidomide (Len) or bortezomib (Bor). Methods: Pts were randomized (3:2) to Isa-Kd (n = 179) or Kd (n = 123). Isa (10 mg/kg IV) was given weekly for 4 weeks, then every 2 weeks. K (20 mg/m² days 1-2, then 56 mg/m²) was given twice-weekly 3 of 4 weeks, and d (20 mg) twice-weekly. The primary endpoint was PFS; key secondary endpoints were very good partial response or better (≥VGPR), minimal residual disease negativity (MRD-), and complete response (CR) rates. Results: Of the 302 randomized pts, 44.7% had 1 prior line, 55.3% had > 1 prior line, 32.8% were Len-refractory, and 30.1% were Bor-refractory. PFS was improved with Isa-Kd vs Kd in pts who received 1 prior line and > 1 prior line, as well as in pts refractory to Len, Len at last regimen, Bor, or Bor at last regimen (Table). The addition of Isa to Kd improved depth of response (≥VGPR, MRD-, and CR rates) in all subpopulations analyzed by prior treatment. Grade ≥3 treatment-emergent adverse events (TEAEs) were generally similar between the prior line subgroups (77.2% [Isa-Kd] vs 64.8% [Kd], 1 prior line; 76.5% [Isa-Kd] vs 69.1% [Kd], > 1 prior line) and the overall safety population (76.8% [Isa-Kd] vs 67.2% [Kd]). Serious AEs were 62.0% vs 48.1% in the 1 prior line subgroup, and 57.1% vs 64.7% in the > 1 prior line subgroup; TEAEs leading to discontinuations were 8.9% vs 11.1%, 1 prior line and 8.2% vs 16.2%, > 1 prior line. Conclusions: The addition of Isa to Kd improved PFS and depth of response, irrespective of prior lines of therapy or refractory status, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd had a manageable safety profile regardless of number of prior lines. Isa-Kd is a potential new treatment option for pretreated pts with RMM. Clinical trial information: NCT03275285. [Table: see text]

Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma

2021 ◽  
pp. JCO.21.01045
Author(s):  
Pieter Sonneveld ◽  
Meletios A. Dimopoulos ◽  
Meral Beksac ◽  
Bronno van der Holt ◽  
Sara Aquino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Primary Study ◽  
Controlled Clinical Trial ◽  
Newly Diagnosed ◽  
Consolidation Treatment ◽  
Minimal Residual

PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.

scholarly journals Case series: MRD negativity assessment using 11C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110303
Author(s):  
Cheong Ngai ◽  
Shaji Kumar ◽  
Garrett Chi-lai Ho ◽  
Sirong Chen ◽  
Chor-sang Chim
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Positron Emission ◽  
Pet Ct ◽  
Subsequent Relapse

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.

Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8026-8026
Author(s):  
Thierry Facon ◽  
Philippe Moreau ◽  
Thomas G. Martin ◽  
Ivan Spicka ◽  
Albert Oriol ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Subgroup Analysis ◽  
Safety Profile ◽  
Residual Disease ◽  
Age Groups ◽  
Progression Free Survival ◽  
Complete Response ◽  
The Elderly ◽  
Efficacy Analysis ◽  
Grade 3

8026 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P=0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts aged <70 and ≥70 years. Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n=179) or Kd (n=123). The primary end point was PFS, as assessed by an independent response committee. We compared outcomes in pts <70 vs ≥70 years; division into different or additional age groups resulted in smaller sample sizes. Results: Of the 302 randomized pts, 71.5% were aged <70 years (Isa-Kd: 70.9%; Kd: 72.4%) and 28.5% were aged ≥70 years (Isa-Kd: 29.1%; Kd: 27.6%). Consistent with the significant improvement of PFS in the overall population, the addition of Isa to Kd resulted in improved PFS independently of age (Table). The CR, ≥very good partial response (VGPR), and MRD- rates were higher with Isa-Kd vs Kd. Within the Isa-Kd arm, CR rate and ≥VGPR rate were similar in elderly and younger pts. MRD- was observed in 32.3% of younger pts and 23.1% of elderly pts with Isa-Kd. In both arms, Grade ≥3 and serious treatment-emergent adverse events (TEAEs) were more frequently reported in elderly pts vs pts <70 years old (Table). For both age groups, the incidence of Grade ≥3 TEAEs was higher whereas the incidence of serious TEAEs was similar between Isa-Kd and Kd. In the elderly subgroup, 3 (5.9%) pts receiving Isa-Kd and 1 (2.9%) receiving Kd had fatal TEAEs (Isa-Kd, infection; Kd, general health deterioration due to progressive disease). The most common Grade ≥3 TEAEs in pts aged <70 and ≥70 years treated with Isa-Kd vs Kd were hypertension (18.3% vs 17.0% [<70 years] and 25.5% vs 26.5% [≥70 years]) and pneumonia (14.3% vs 9.1% [<70 years] and 21.6% vs 20.6% [≥70 years]). Conclusions: The addition of Isa to Kd improved PFS and quality of response in elderly pts, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd provides a potential new treatment option for elderly pts with RMM. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]

Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8042-8042
Author(s):  
Ivan Spicka ◽  
Philippe Moreau ◽  
Thomas G. Martin ◽  
Thierry Facon ◽  
Gracia Martinez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Subgroup Analysis ◽  
Safety Profile ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Disease Response ◽  
Efficacy Analysis ◽  
New Treatment

8042 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P= 0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts with high-risk cytogenetics [t(4;14), del(17p), and t(14;16)] and/or gain(1q21). Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n = 179) or Kd (n = 123). High-risk cytogenetics was assessed by central laboratory analysis and defined as ≥1 of the following: del(17p): 50% cutoff; t(4;14) or t(14;16): 30% cutoff. Assessment of gain(1q21) was prespecified as ≥3 copies: 30% cutoff. Results: Of the randomized pts, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk cytogenetic abnormality (CA); 26.3% (Isa-Kd) and 25.2% (Kd) had isolated gain(1q21). The addition of Isa to Kd improved PFS for pts with ≥1 high-risk CA and standard-risk pts (Table); pts with t(4;14) (HR 0.549; 95% CI, 0.232–1.301) had a more pronounced treatment effect than pts with del(17p) (HR 0.837; 95% CI, 0.281–2.496). A clear PFS benefit with Isa-Kd was also seen for pts with isolated gain(1q21) and gain(1q21) combined with other high-risk CA (Table). The trend toward improved CR, ≥very good partial response (VGPR), and MRD- rates with the addition of Isa was more pronounced in pts with gain(1q21) than in pts with high-risk CA alone. Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd vs Kd, but the incidence of serious and fatal TEAEs was similar with both arms for high-risk pts (Table). Conclusions: The addition of Isa to Kd improved PFS in pts with high-risk CA and disease response in pts with gain(1q21) isolated or combined with high-risk CA, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA population. Isa-Kd is a potential new treatment option for the difficult-to-treat subgroup of pts with RMM and high-risk cytogenetics. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]

Contemporary therapy efficacy for high-risk multiple myeloma: A systematic review.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19536-e19536
Author(s):  
Afia Ashraf ◽  
Udhayvir Singh Grewal ◽  
Prem Thirunagari ◽  
Ahsan Wahab ◽  
Ammara Majeed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Residual Disease ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Complete Response ◽  
Outcome Data ◽  
Drug Conjugates ◽  
Car T ◽  
Standard Risk

e19536 Background: Multiple Myeloma (MM) is a heterogeneous disease. High Risk (HR) MM is defined as the presence of abnormal cytogenetics i.e. t(4:14), t(14:16), t(14:20), del(17/17p), non hyperdiploidy and gain (1q). HR MM is a treatment challenge. We aim to explore efficacy of anti-myeloma therapy for newly diagnosed (ND) and relapsed/refractory (RR) HR MM. Methods: We used Pubmed, Ebsco and MBASE to select 18 trials with outcome data on ND (n = 598) and RR(n = 726) HR MM (n = 1321), after extensive review, treatment efficacy (CR, VGPR, ORR) and survival (mPFS, OS) data was extracted. Results: In HR MM the range of overall response rate (ORR) was 31%-100% (Standard Risk (SR): 56%-94.7%), complete response (CR) was 10%-58.3% (SR: 7%-38.1%) and very good partial response (VGPR) was 15%-88.3% (SR: 25%-63%). In ND HR patients, range of ORR was 71.2% - 86.2% (SR: 71.2% - 91.7%) and CR was 35% - 58.3% (SR: 22%-35%) and median progression free survival (mPFS) was 18 months (m) - 31.3m (SR: 31.3m – Not Reached). In RR HR patients, range of ORR was 31% – 85.2% (SR: 56%-94.7%) and CR was 10%-29.2% (SR: 7%-38.1%) and mPFS was 3.3m - 23.1m (SR: 4m - Not Reached). In RR HR MM, Daratumumab ( Dara) , lenalidomide (R) and dexamethasone (d) combination resulted in highest minimal residual disease (MRD) negativity 21.4%. In RR HR, Carfilzomib (Car)- R-d resulted in the longest mPFS of 23.1m (SR: 29.6m) followed by (Dara)-R-d of 22.6m (SR:NR) and Ixazomib (I)- R-d of 21.4m (SR:20.6). In ND HR, Bortezomib (V) with thalidomide (T)- d resulted in longest mPFS of 23.5m (SR: NR) and OS of 56.6m followed by Cyclophosphamide (Cy)-T-d of 20m (SR:34m) and (Dara)-V- Melphalan(M) and Prednisone of 18m (SR:NR). Quadruplet therapy in ND with Cy- V – d with pegylated liposomal doxorubicin resulted in the highest CR 58.3% and mPFS of 31.3m (~8m longer). Conclusions: Cytogenetically HR MM achieved high ORR, CR and VGPR similar to SR MM yet, the PFS and OS in HR (mPFS: 11.2m - 31.3m) was significantly shorter than SR (mPFS: 19m - Not Reached) representing poor prognosis. Promising strategies and targeted therapies that are currently evolving include antibody based combination therapy (3 or 4 drugs), various CAR-T cells constructs, targeted inhibitors, and antibody-drug conjugates.

Pomalidomide (CC4047) Plus Low-Dose Dexamethasone As Therapy for Relapsed Multiple Myeloma

2009 ◽  
Vol 27 (30) ◽  
pp. 5008-5014 ◽  
Author(s):  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Low Dose ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
High Risk Disease ◽  
Grade 3

Purpose Thalidomide and lenalidomide are immunomodulatory drugs (IMiDs) that produce high remission rates in the treatment of multiple myeloma. Pomalidomide is a new IMiD with high in vitro potency. We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma. Patients and Methods Pomalidomide was administered orally at a dose of 2 mg daily on days 1 through 28 of a 28-day cycle. Dexamethasone 40 mg daily was administered orally on days 1, 8, 15, and 22 of each cycle. Responses were recorded using the criteria of the International Myeloma Working Group. Results Sixty patients were enrolled. Thirty-eight patients (63%) achieved confirmed response including complete response in three patients (5%), very good partial response in 17 patients (28%), and partial response in 18 patients (30%). Responses were seen in 40% of lenalidomide-refractory patients, 37% of thalidomide-refractory patients, and 60% of bortezomib-refractory patients. Responses were seen in 74% of patients with high-risk cytogenetic or molecular markers. Toxicity consisted primarily of myelosuppression. Grade 3 or 4 hematologic toxicity consisted of anemia (5%), thrombocytopenia (3%), and neutropenia (32%). One patient (1.6%) had a thromboembolic event. The median progression-free survival time was 11.6 months and was not significantly different in patients with high-risk disease compared with patients with standard-risk disease. Conclusion The combination of pomalidomide and low-dose dexamethasone is extremely active in the treatment of relapsed multiple myeloma, including high response rates in patients refractory to other novel agents.

scholarly journals Sustained Minimal Residual Disease Negativity With Daratumumab in Newly Diagnosed Multiple Myeloma: MAIA and ALCYONE

Blood ◽  
2021 ◽  
Author(s):  
Jesus F. San-Miguel ◽  
Hervé Avet-Loiseau ◽  
Bruno Paiva ◽  
Shaji K Kumar ◽  
Meletios A A Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pooled Analysis ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Intent To Treat ◽  
Minimal Residual

In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone; D-Rd) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone; D-VMP). Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE. MRD assessments using next-generation sequencing (10-5) occurred for patients achieving complete response (CR) or better, and after ≥CR at 12, 18, 24, and 30 months from the first dose. Progression-free survival (PFS) by MRD status and sustained MRD negativity lasting ≥6 and ≥12 months were analyzed in the intent-to-treat population and among patients achieving ≥CR. In MAIA, (D-Rd, n=368; Rd, n=369), and ALCYONE (D-VMP, n=350; VMP, n=356), the median duration of follow-up was 36.4 months and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting ≥6 and ≥12 months were associated with improved PFS, regardless of treatment group. However, daratumumab-based therapy improved rates of MRD negativity lasting ≥6 months (D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5%) and ≥12 months (D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8%), both of which translated to improved PFS versus control groups. In a pooled analysis, patients who were MRD negative had improved PFS versus patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. ClinicalTrials.gov identifier NCT02252172 (MAIA); NCT02195479 (ALCYONE).

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