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

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.

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

Leukemia ◽

10.1038/s41375-020-0711-6 ◽

2020 ◽

Vol 34 (7) ◽

pp. 1875-1884 ◽

Cited By ~ 20

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.

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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

Annals of Hematology ◽

10.1007/s00277-021-04534-8 ◽

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.

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

Therapeutic Advances in Hematology ◽

10.1177/2040620718816699 ◽

2019 ◽

Vol 10 ◽

pp. 204062071881669 ◽

Cited By ~ 7

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.

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

Blood Cancer Journal ◽

10.1038/s41408-021-00507-2 ◽

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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Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study

BMC Cancer ◽

10.1186/s12885-021-08881-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shebli ATRASH ◽

Philippe THOMPSON-LEDUC ◽

Ming-Hui TAI ◽

Shuchita KAILA ◽

Kathleen GRAY ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Outcomes ◽

Real World ◽

Chart Review ◽

Response Rate ◽

Progression Free Survival ◽

Treatment Patterns ◽

Free Survival ◽

Kaplan Meier ◽

Line Of Therapy

Abstract Background Daratumumab, a CD38 monoclonal antibody, has demonstrated efficacy as monotherapy and combination therapy across several indications, both among newly-diagnosed and refractory patients with multiple myeloma (MM). However, there is limited evidence on treatment patterns and effectiveness of daratumumab in the real-world setting, particularly in first line (1 L). This study aimed to describe real-world treatment patterns and clinical outcomes among patients initiating daratumumab across different lines of therapy. Methods A retrospective chart review of adult patients with MM initiating daratumumab between November 2015 and March 2021 was conducted at two clinical sites in the United States. De-identified patient-level data were abstracted in an electronic case report form. Patient characteristics and treatment patterns were described. Clinical outcomes including overall response rate (ORR), progression-free survival, and time to next line of therapy were reported using descriptive statistics and stratified by line of therapy (1 L, second line [2 L] or third line or later [3 L+]). A sub-group analysis evaluated treatment patterns and ORR among patients re-treated with daratumumab. Results A total of 299 patients were included in the study (mean age: 68 years; 55% male). Among them, 26 were 1 L patients, 66 were 2 L patients, and 207 were 3 L+ patients; 110 patients (36.8%) received a stem cell transplant prior to daratumumab initiation. The mean duration of follow-up was 10 months among 1 L patients and 19 months among 2 L and 3 L+ patients. Patients who initiated daratumumab in 1 L had a 100% ORR, while those initiating in 2 L and 3 L+ had an ORR of 78.8 and 65.2%, respectively. Among re-treated patients, ORR was 66.7% during the first treatment segment, and 52.9% during the second treatment segment. Kaplan-Meier rates of progression-free survival at 12 months were 89.9, 75.2, and 53.1% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Kaplan-Meier rates of time to next line of therapy at 12 months were 94.1, 73.4, and 50.0% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Conclusions These findings suggest that daratumumab-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1 L.

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

Future Oncology ◽

10.2217/fon-2020-1003 ◽

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.

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

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155221995532 ◽

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.

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Overall survival with oral selinexor plus low‐dose dexamethasone versus real‐world therapy in triple‐class‐refractory multiple myeloma

eJHaem ◽

10.1002/jha2.120 ◽

2020 ◽

Author(s):

Paul G. Richardson ◽

Sundar Jagannath ◽

Ajai Chari ◽

Dan T. Vogl ◽

Meletios A. Dimopoulos ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Real World ◽

Low Dose ◽

Refractory Multiple Myeloma

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Lenalidomide and Low Dose Dexamethasone Plus Elotuzumab or Carfilzomib for Relapsed or Refractory Multiple Myeloma: A Comparison of Progression-Free Survival with Reconstructed Individual Participant Data

BioMed Research International ◽

10.1155/2018/9057823 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Shuo Li ◽

Xiang-Yu Meng ◽

Souraka Tapara Dramani Maman ◽

Yong-Nong Xiao ◽

Sheng Li

Keyword(s):

Multiple Myeloma ◽

Survival Analysis ◽

Low Dose ◽

Progression Free Survival ◽

Disease Stage ◽

Free Survival ◽

Kaplan Meier ◽

Significant Difference ◽

Baseline Status ◽

Individual Participant

Background. Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports. Methods. We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated. Results. Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67]). Conclusion. The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.

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