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]

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 &lt; .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]

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 (&lt;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.

MASS-FIX versus standard methods to predict for PFS and OS among multiple myeloma patients participating on the STAMINA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8009-8009
Author(s):  
Angela Dispenzieri ◽  
Amrita Y. Krishnan ◽  
Bonnie Arendt ◽  
Surendra Dasari ◽  
Yvonne Adeduni Efebera ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Multiple Testing ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Independent Effect ◽  
Next Generation ◽  
Different Response

8009 Background: Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses have been associated with better progression free survival (PFS) and overall survival (OS). Serum (SIFE) and urine immunofixation are the currently used markers for biochemical documentation of CR after which marrow is tested for plasma cell clearance. Next generation flow cytometry and sequencing are used to document the presence of minimal residual disease (MRD). Mass spectrometry of blood by MALDI (Mass-Fix) is a new simple, inexpensive, sensitive, and specific means of detecting monoclonal immunoglobulins. To better test the hypothesis that Mass-Fix is superior to existing methodologies to predict for survival outcomes—especially SIFE-- samples from the STAMINA trial (NCT01109004), a trial comparing 3 transplant approaches among patients who have already received induction, were employed. Methods: Five-hundred and seventy-five patients were included. Samples from enrollment post-induction (post-I) and 1-year post enrollment (1YR) were tested when available. Four response parameters were assessed univariately: Mass-Fix, SIFE, complete response, and MRD by next generation flow cytometry. Mass spectrometry spectra were evaluated in a blinded fashion. Complete response was according to the 2006 International Myeloma Working Group criteria. Multivariate Cox proportional hazard models using stepwise regression were developed to explore the independent effect of the different response parameters on PFS and OS and interactions with other risk factors. Results: Of the 4 response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses (Table). Of the 4 post-I measurements, only MRD predicted for PFS; however, Mass-Fix was the only post-I measurement to predict for OS. Of all the 1-year measures, both 1YR Mass-Fix and 1YR MRD positivity predicted for inferior PFS and OS. In models including MRD and Mass-Fix, SIFE and CR were not prognostic for PFS or OS. Conclusions: Mass-Fix is a powerful means to track monoclonal proteins. The full utility of Mass-Fix was not exploited given the absence of a diagnostic sample and the fact that only serum (and not urine) was tested. Despite these limitations, it performed well at pre-induction and at 1 year. Mass-Fix provides a convenient and non-invasive means of predicting for myeloma outcomes. Clinical trial information: NCT01109004. [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.

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

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Kihyun Kim ◽  
Chang Ki Min ◽  
Youngil Koh ◽  
Kenichi Ishizawa ◽  
Sung-Hyun Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Residual Disease ◽  
East Asian ◽  
Progression Free Survival ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Asian Patients ◽  
Number Of Patients ◽  
East Asian Patients

e20015 Background: 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 patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

DREAMM-9: Phase III study of belantamab mafodotin plus VRd versus VRd alone in transplant-ineligible newly diagnosed multiple myeloma (TI NDMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8556-TPS8556 ◽  
Author(s):  
Saad Zafar Usmani ◽  
Evangelos Terpos ◽  
Wojt Janowski ◽  
Hang Quach ◽  
Sarah West ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Open Label

TPS8556 Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is the standard of care for transplant-eligible and TI NDMM, but relapse is usually inevitable. The median progression-free survival (PFS) is ~3 years for patients with TI NDMM, and with each relapse, the duration of response (DoR) diminishes, highlighting the need for novel, effective, targeted agents. Single-agent belantamab mafodotin is a first-in-class B-cell maturation antigen–binding, humanized, afucosylated, monoclonal immunoconjugate, showing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma ( Lancet Oncol2020). Preclinical work suggests belantamab mafodotin plus bortezomib or lenalidomide enhances anti-myeloma activity. Therefore, studying clinical activity of belantamab mafodotin in combination with these agents is warranted. Methods: DREAMM-9 (NCT04091126) is a two-part, open-label study to determine efficacy and safety of single-agent belantamab mafodotin with VRd vs. VRd alone in patients with TI NDMM. Patients aged ≥18 years with ECOG status 0–2 and adequate organ system functions will be eligible. Part 1 (dose selection) will evaluate safety/tolerability of belantamab mafodotin with VRd administered by single (Day 1) or split dosing (Days 1 and 8) in ≤5 cohorts (n = 12/cohort): 1.9 mg/kg, 2.5 mg/kg split and single, and 3.4 mg/kg split and single. Six more patients may be added to cohort(s) most likely to be selected as recommended Phase III dose (RP3D). Dose-limiting toxicities and adverse events (AEs) will be assessed, and belantamab mafodotin RP3D determined through modified toxicity probability interval criteria. Part 2 (randomized Phase III) will determine efficacy and safety of belantamab mafodotin at RP3D with VRd vs. VRd alone (n = 750) in two arms randomized 1:1. Dual primary endpoints will be rate of minimal residual disease (MRD) negativity and PFS. Secondary endpoints will be response rates (overall response, complete response, very good partial response or better, sustained MRD negativity), DoR, time to progression, and overall survival. Safety assessment will include AEs, serious AEs and ocular findings. In both parts, belantamab mafodotin will be given with VRd for eight induction cycles and then with Rd for maintenance until disease progression or unacceptable toxicity. Funding: GlaxoSmithKline (209664). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04091126 .

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