scholarly journals Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US

2021 ◽  
Author(s):  
Faith Davies ◽  
Robert Rifkin ◽  
Caitlin Costello ◽  
Gareth Morgan ◽  
Saad Usmani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Comparative Effectiveness ◽  
Proteasome Inhibitors ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
The Us ◽  
Cox Proportional Hazard Models ◽  
Comparative Effectiveness Analysis ◽  
Line Of Therapy

AbstractMultiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum’s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Real-world treatment patterns in relapsed/refractory multiple myeloma: Clinical and economic outcomes in patients treated with pomalidomide or daratumumab

2021 ◽  
pp. 107815522199553
Author(s):  
Joshua Richter ◽  
Vamshi Ruthwik Anupindi ◽  
Jason Yeaw ◽  
Suneel Kudaravalli ◽  
Stojan Zavisic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Treatment Options ◽  
Proteasome Inhibitors ◽  
Economic Outcomes ◽  
Office Visits ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Real World Evidence ◽  
New Treatment

Introduction Real-world evidence on later line treatment of relapsed/refractory multiple myeloma (RRMM) is sparse. We evaluated clinical outcomes among RRMM patients in the 1-year following treatment with pomalidomide or daratumumab and compared economic outcomes between RRMM patients and non-MM patients. Patient and Methods Adult patients with ≥1 claim of pomalidomide or daratumumab were identified between January 2012 and February 2018 using IQVIA PharMetrics® Plus US claims database. Patients were required to have a diagnosis or treatment for MM and a claim of any immunomodulatory drugs and proteasome inhibitors before the index date. Mean time to new therapy, overall survival (OS) using Kaplan-Meier curve and adverse events (AEs) were reported over the 1-year post-index period. RRMM patients were also matched to a non-MM comparator cohort and economic outcomes were compared between the two cohorts. Results 289 RRMM patients were matched to 1,445 patients without MM. Most prevalent hematological AE was anemia (72.0%) and non-hematological AE was infections (75.4%). Mean (SD) time to a new treatment was 4.7 (5.3) months and median OS was 14.6 months. RRMM patients had significantly higher hospitalizations and physician office visits (Both P < .0001) compared to non-MM patients. Adjusting for baseline characteristics, patients with RRMM had 4.9 times (95% CI 3.8-6.4, P < .0001) the total healthcare costs compared with patients without MM. The major driver of total costs among RRMM patients was pharmacy costs (67.3%). Conclusion RRMM patients showed a high frequency of AEs, low OS, and a substantial economic burden suggesting need for effective treatment options.

scholarly journals Renal response in real-world carfilzomib- vs bortezomib-treated patients with relapsed or refractory multiple myeloma

2021 ◽  
Vol 5 (2) ◽  
pp. 367-376
Author(s):  
Shaji Kumar ◽  
Alan Fu ◽  
Ruben Niesvizky ◽  
Sundar Jagannath ◽  
Ralph Boccia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Positive Association ◽  
Complete Response ◽  
Rank Test ◽  
Renal Response ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Models ◽  
Rate Ratios

Abstract In the phase 3 ENDEAVOR study, carfilzomib-dexamethasone (Kd) improved survival over bortezomib-dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), regardless of baseline renal function. This real-world study compared renal response in patients with RRMM (1-3 prior lines) and renal impairment (estimated glomerular filtration rate ≤50 mL/min) treated with Kd vs Vd. Electronic medical records data from the Oncology Services Comprehensive Electronic Records database were assessed (from January 2012 through February 2018). Time to renal response (defined according to International Myeloma Working Group criteria) was evaluated using the Kaplan-Meier method and log-rank test. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for renal overall response (ROR) and renal complete response (RCR) using Cox proportional hazard models adjusted for baseline covariates. Included were 543 Kd-treated and 1005 Vd-treated patients. In line 2 (2L), compared with Vd, Kd achieved significantly higher ROR (51.4% vs 39.6%; P &lt; .0001) and RCR (26.6% vs 22.2%; P = .0229). After baseline covariate adjustment, 2L patients receiving Kd vs Vd were 45% more likely to achieve ROR (IRR, 1.45; 95% CI, 1.18-1.78), and 68% were more likely to achieve RCR (IRR, 1.68; 95% CI, 1.24-2.28). The renal response benefit with Kd remained consistent in 2L to line 4 (4L). In a combined analysis of patients receiving Kd and Vd (2L and 2L-4L), renal responders had longer overall survival and time to next treatment than renal nonresponders. These results demonstrate improved real-world effectiveness of Kd over Vd in RRMM renal rescue, and the positive association between renal response and improved survival.

scholarly journals Real-world treatment patterns, healthcare use and costs in triple-class exposed relapsed and refractory multiple myeloma patients in the United States

2020 ◽  
Author(s):  
Deepu Madduri ◽  
May Hagiwara ◽  
Kejal Parikh ◽  
Corey Pelletier ◽  
Thomas E Delea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Proteasome Inhibitors ◽  
The United States ◽  
Healthcare Resource Utilization ◽  
Treatment Patterns ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Line Of Therapy

Aim: To estimate treatment patterns and healthcare costs among triple-class exposed relapsed and refractory multiple myeloma (RRMM) patients. Materials & methods: Eligible patients had ≥1 line of therapy (LOT) each of proteasome inhibitors, immunomodulatory drugs and daratumumab in December 2015–September 2018 and received a new LOT. Results: A total of 154 patients were included with a median follow-up of 6.2 months. Median time from diagnosis to new LOT was 41.0 months. Kaplan–Meier estimate of median time to therapy discontinuation was 4.2 months. Mean per-patient, per-month MM-related costs were 35,657 US dollars. Most frequently observed regimens were lenalidomide or pomalidomide + daratumumab (18.2%), lenalidomide or pomalidomide + proteasome inhibitors (15.6%) and lenalidomide or pomalidomide monotherapy (11.0%). Conclusion: Triple-class exposed RRMM patients receive heterogeneous treatments for a short duration with high healthcare resource utilization and costs.

scholarly journals Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1509
Author(s):  
Evangelos Terpos ◽  
Panagiotis Repousis ◽  
Chrysavgi Lalayanni ◽  
Evdoxia Hatjiharissi ◽  
Theodora Assimakopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Low Dose ◽  
Safety Data ◽  
Progression Free Survival ◽  
Routine Care ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Line Of Therapy

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade  ≥  3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

Real-world treatment patterns and outcomes of triple-exposed multiple myeloma patients treated in community oncology practices in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18727-e18727
Author(s):  
Robert Smith ◽  
Mei Xue ◽  
Natalie Dorrow ◽  
Prateesh Varughese ◽  
Cosima Hogea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Real World ◽  
Proteasome Inhibitors ◽  
Office Visit ◽  
The United States ◽  
Subsequent Treatment ◽  
Treatment Patterns ◽  
Duration Of Therapy ◽  
The Us

e18727 Background: Treatment for multiple myeloma (MM) over the past decade has significantly improved survival. In particular, 3 drug classes have altered the treatment paradigm for MM patients: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies (anti-CD38s). Despite these advances, the majority of patients with MM will become refractory to PIs, IMiDs, and anti-CD38s, and limited evidence indicates these patients have poor outcomes. A retrospective study in the US showed that 275 patients treated at 14 academic institutions with prior exposure to a PI, IMiD, and anti-CD38 had median overall survival of 9.2 months. The aim of this study was to evaluate real-world treatment patterns and outcomes (duration of therapy and overall survival) of patients who had been treated with a PI, IMiD, and anti-CD38 in community practices in the US. Methods: This retrospective observational study was conducted using the Integra Connect (IC) database. The IC database includes electronic health data from structured and unstructured fields from 12 community practices on the East and West Coast of the US. Adult patients with ≥2 ICD-9/ICD-10 codes for MM on at least 2 separate dates, who received MM treatment between Jan 1, 2016, and Dec 31, 2019, with treatment history that included at least one PI, one IMiD, and one anti-CD38 (triple exposed), and initiated a subsequent line of therapy (s-LOT) after becoming triple exposed, were included. Duration of length of s-LOT was defined as number of days from start of s-LOT to last-day supply of s-LOT. Overall survival was defined as the length of time from start of s-LOT through death or the date of the last office visit. Results: A total of 501 patients were included in this analysis. The median age of patients was 64.9 years; 50% were male; 50% had commercial insurance. 82.8% of patients had ECOG 0 or 1 at diagnosis and had received a median of 3 prior lines of therapy (LOTs) before initiating s-LOT. Prior to initiating s-LOT, 91% had been exposed to bortezomib, 81% to carfilzomib, 94% to lenalidomide, 82% to pomalidomide, and 100% to daratumumab. In s-LOT, 95% received treatment that included same drug or same drug class (30% received bortezomib, 48% carfilzomib, 31% lenalidomide, 47% pomalidomide, and 31% daratumumab). The median duration of s-LOT was 78 days and median survival was 10.3 months (308 days) from initiation of s-LOT. Conclusions: For triple-class exposed patients, there is a lack of consensus on the most efficacious approach to subsequent treatment. The present study shows a significant amount of retreatment with previously used agents or classes among these patients with short duration of therapy and poor survival. As has been previously noted, new strategies and agents targeting novel aspects of MM are needed to improve outcomes for these patients. Disclosures: This study (213286) was sponsored by GlaxoSmithKline.

scholarly journals A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting

2019 ◽  
Vol 10 ◽  
pp. 204062071881669 ◽  
Author(s):  
Robert M. Rifkin ◽  
Rohan Medhekar ◽  
E. Susan Amirian ◽  
Kathleen M. Aguilar ◽  
Thomas Wilson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Real World Data ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Community Oncology ◽  
First Relapse ◽  
Line Of Therapy

Background: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. Methods: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox modeling. Results: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd ( n = 112; 71.8%), VRd ( n =27; 17.3%), or VCyd ( n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71–NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24–12.71; VCyd: 6.5 months, 95% CI: 3.02–12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11–0.37), compared with VRd. Conclusions: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

Characteristics of adult multiple myeloma patients receiving carfilzomib in a U.S. community oncology setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19517-e19517
Author(s):  
Robert M. Rifkin ◽  
Rohan Medhekar ◽  
Khalid Mezzi ◽  
Kathleen Aguilar ◽  
Thomas Wilson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Real World ◽  
Older Patients ◽  
Patient Characteristics ◽  
Refractory Multiple Myeloma ◽  
Female Patients ◽  
Community Oncology ◽  
The Us ◽  
Baseline Characteristics

e19517 Background: Carfilzomib (K) is indicated for treatment of relapsed or refractory multiple myeloma (MM). We studied the characteristics of patients receiving K in the US Oncology Network’s (USON) EHR database. Methods: Patients ≥18 years who received a K-containing regimen between 11/01/2013-02/29/2016, were not in a clinical trial, and had ≥2 visits at a USON clinic were eligible. Baseline characteristics were compared between patients who received a K-based doublet, triplet or other regimen (monotherapy or >3 treatments). Results: Of the 718 patients who received a K-based regimen during the study period, 219 (30.5%) had doublet regimens, 287 (40.0%) received triplet regimens and 212 (29.5%) received other regimens; 494 (68.8%) received regimens with ≥3 therapies. Mean age was 69.7 and 64.7 years among patients on doublets and triplets, respectively. A higher proportion of female patients received doublets (53.0%) (Table). There were no differences in ISS stage or number of comorbidities across patients receiving doublets, triplets, or other regimens. Conclusions: In this real-world analysis of K-regimens, a majority of patients received triplet regimens. Older patients received doublet regimens more frequently. The influence of regimen on outcomes controlling for patient characteristics and prior treatments among MM patients receiving K-based regimens should be studied. [Table: see text]

scholarly journals KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Sundar Jagannath ◽  
Yi Lin ◽  
Hartmut Goldschmidt ◽  
Donna Reece ◽  
Ajay Nooka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Eligibility Criteria ◽  
T Cell Therapy ◽  
Refractory Multiple Myeloma ◽  
Single Data ◽  
Line Of Therapy

AbstractPatients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.

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