Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple ...myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.
We analysed trends over time in palliative first-line chemotherapy in patients with locally advanced or metastatic esophagogastric cancer. Special focus was on frequency and quality of HER2-testing ...and trends in drug use in combination with trastuzumab. Earlier published data about patients treated outside clinical studies showed a relatively low rate of HER2-testing and insufficient test quality. A total of 2,808 patients retrospectively documented in Therapiemonitor ® from 2006 to 2013 were analysed regarding treatment intensity and trends in used drugs. Data on HER2-testing and therapies were analysed in two cohorts documented in 2010 and 2011 (1) compared to 2012 and 2013 (2). Treatment intensity increased: 49.3% of patients received at least a triplet in 2013 compared to 10.1% in 2006. In cohort 2 HER2 expression was tested in 79.1% of the cases. Still, in 26.9% testing was not done as requested by guidelines. Good performance status, multiple metastases, age ≤ 65 years, the objective “to prevent progression,” good cognitive capabilities, estimated good compliance, and social integration positively influenced the probability of HER2-testing; comorbidities negatively affected it. Usage of the combination of fluoropyrimidines and cisplatin with trastuzumab declined from 67% in cohort 1 to 50% in cohort 2.
Background: The RRMM treatment landscape has increased in complexity in recent years due to the availability of novel agents. In this study, we evaluated treatment patterns over 3 years in real-world ...RRMM pts treated with regimens containing one or more of the following agents: carfilzomib (K), bortezomib (V), lenalidomide (R), pomalidomide (P), ixazomib (I), daratumumab (D), and elotuzumab (E).
Methods: We retrospectively analysed data from a German longitudinal database (TherapyMonitor) for pts receiving RRMM treatment (2nd-line 2L and beyond) between January 2016 and December 2018. Patient demographics, treatment details and clinical characteristics were described by line of treatment and regimen for a patients most recent treatment. Treatment patterns were described by year of treatment initiation (2016, 2017 or 2018).
Results: Of the total study population of 2033 RRMM pts, the most recent treatment line was 2L for 1047 and 3L+ for 986 pts. 2L/3L+ pts had a median age of 70/71 years (22%/27% >75 years; most were aged 66-75 years); 57%/61% had ISS stage III; 43%/50% had ECOG ≥2; 10%/9% had renal dysfunction; 56%/56% had ≥1 comorbidity and 14%/17% had received stem cell transplantation at 1L, respectively. In 2L pts, across 2016-2018, R non-triplet (24%) was the most common treatment regimen, with 18% and 10% of pts receiving K+R and D+R triplets, respectively. In 3L+ pts, the most common treatment regimens were D-based (29% 12% non-triplet, 9% D+V triplet and 8% D+R triplet), P non-triplet (9%), K non-triplet or I/R triplet (both 8%), and R non-triplet (7%). In 2L pts, the most frequent prior treatments were V triplets/non-triplets (45%/19%) and R non-triplets (15%). In 3L+ pts, the most frequent prior treatments were R non-triplets (27%) and K non-triplets (16%). Triplet regimens were mostly administered in 2L to pts ≤65 years. Age had no clear impact on 3L+ treatment patterns. ECOG status impacted treatment patterns in 2L (doublet therapy more frequent in ECOG ≥2) but not in 3L+ (most pts had ECOG ≥2 but were frequently treated with E/D/I triplets).
Regarding trends over time (2016 to 2018), considering all treatments, V triplet+ was the most frequently used regimen prior to 2L (37 to 43%), while V-non-triplet use decreased (32% to 19%) and R-based non-triplet use doubled (7% to 16%). In 2L, K-based regimen use increased from 25% to 38%, mainly due to increased use of K non-triplet (10% to 19%). 2L D-based triplet use increased from 0% to 15% and use of R non-triplet halved (55% to 27%). Patients receiving K- or D-based triplet or R non-triplet at 2L predominantly received V triplet regimens at 1L. Most 2L pts receiving non-triplet regimens also received V or R non-triplets at 1L. These trends suggest a shift in use of R non-triplets from 2L to 1L, replacing 1L V non-triplets and resulting in greater use of 2L K non-triplets.
Specifically, for 2L in 2018, of the 27% of pts treated with R non-triplets (Figure), the most common 1L regimens were V-triplet (44%), V non-triplet (29%) and other non-novel agent containing regimens (15%). For the 19% of pts receiving 2L K+R triplet regimen, the most common 1L regimens were V-triplet+ (66%), other regimens containing novel agents (24%) and V and R non-triplets (5% each). Of the 19% of pts receiving 2L K non-triplet regimens, R non-triplet (35%), V non-triplet (28%) and V-triplet+ (24%) were the most common 1L treatments. For the 11% of pts receiving 2L DR-triplet regimens, V-triplet+ (57%), other regimens containing novel agents (20%), R non-triplet (14%), and V non-triplet (6%) were the most common 1L treatments.
Conclusions: Multiple approvals of novel RRMM agents in Europe resulted in changes in the treatment landscape, with a more immediate impact in countries with earlier access to new drugs. In this RRMM population we found increased 1L use of R non-triplets and decreased V non-triplet use between 2016-2018. Use of D-based regimens increased in 2L; P-, I-, and E-based regimens were infrequently used in 2L (≤4% in 2018). Pts receiving 1L non-triplets generally received 2L non-triplet treatment; those receiving 1L triplet generally also received 2L triplet treatment. 3L pts were mostly R-pretreated due to high use of 2L R-based triplets. Germany may serve as an example for the adoption of novel treatments as there is adoption of all RRMM agents approved since 2016.
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Merz:Takeda Vertrieb GmbH: Other: Travel grants, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Janssen: Other: Travel grants; Abbvie: Other: Travel grants; Celgene: Other: Travel grants. Patel:Amgen: Employment. Kutikova:Amgen: Employment. Lebioda:Amgen: Employment. Schoehl:Amgen: Employment. Kellermann:Takeda: Research Funding; Amgen: Research Funding; BMS: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Sanofi: Research Funding. Goldschmidt:Dietmar-Hopp-Stiftung: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Molecular Partners: Research Funding; MSD: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Research Funding; Janssen: Consultancy, Research Funding; John-Hopkins University: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; John-Hopkins University: Research Funding.
To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe.
German and Italian administrative ...claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms.
Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%).
From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.
Background
Recently, treatment options for RRMM have increased substantially with multiple approvals of novel agents/combination, making the treatment algorithm increasingly complex, with changes ...driven chiefly by access to novel agents/regimens. Furthermore, patient (pt) and disease characteristics have a profound impact on treatment decisions. To understand the impact of recently approved novel regimens on real-world (RW) treatment patterns, we conducted a multi-national survey to investigate the management of RRMM across Europe.
Methods
Retrospective, anonymized data from RRMM pts, treated in academic or community hospitals/clinics in 8 countries were extracted from Jan 2016 to Dec 2018. Data were analyzed overall and for Germany, Austria, and Switzerland (DACH) vs other countries (Belgium, France, Greece, Spain and UK) due to differences in treatment access.
Results
The cumulative number of pts included was 2782 in 2016, 3902 in 2017, and 4658 in 2018. Of the pts enrolled in 2016, 2017 and 2018, 40%, 49% and 51%, respectively, were in 3rd+ line (≥3L), potentially reflecting the increasing availability of treatment options for RRMM and extended survival in MM. Median age at diagnosis in pts enrolling in 2016, 2017, and 2018, was 68, 69, and 70 years, respectively, with 23%, 24%, 26% aged >75 years, underlining the fact that MM remains a disease of the elderly. The data revealed a difficult-to-treat RW population: 31%-36% of pts had an ECOG PS ≥2 at 2nd line (2L) in 2016-2018; increasing to 44%-49% at 4th+ lines (≥4L). At 2L, 42%-45% of pts presented ≥1 treatment-dependent comorbidity in 2016-2018, including hypertension (23-27%) and renal impairment (9-10%). Cytogenetic risk, evaluated in 38%-42% of pts at initial diagnosis, was reported as high in 8%-10% of the total population. Treatment initiation due to biochemical relapse was reported in 33%/36% of pts at 2L/3L in 2016, and in 30%/28% in 2018, indicating that ~1/3 of pts manifested an asymptomatic rather than clinical relapse.
The proportion of pts treated with triplet regimens increased from 26%, 26%, and 30% at 2L, 3L and ≥4L in 2016 to 43%, 40%, and 38% in 2018, reflecting the adoption of newly approved triplets in RRMM, particularly in DACH countries. Use of proteasome inhibitor (PI)-based regimens increased from 35%, 30% and 34% at 2L, 3L and ≥4L in 2016, to 43%, 37% and 37% in 2018, driven by increased/earlier use of novel PIs (carfilzomib and ixazomib). These trends were more obvious in DACH, highlighting the impact of earlier access to modern treatment in these countries. Similarly, the proportion of pts on daratumumab-based regimens increased from 0, 5%, and 20% at 2L, 3L and ≥4L in 2016, to 10%, 24% and 31% in 2018.
From 2016 to 2018, prior IMiD exposure at 2L increased from 11% to 20% in DACH, but remained stable at 42% in other countries; at 3L, there was an increase from 77% to 82% in all countries reflecting the uptake of novel triplet combinations. Most pts were IMiD-exposed or IMiD-refractory at ≥4L. Regarding the treatment algorithm, the rate of PI-based treatment at 1L was 74%-75%. PI- to IMiD-based therapy was the commonest treatment sequence from 1L to 2L, at 64%-66%, while PI- to PI-based therapy at 1L to 2L increased from 22% in 2016 to 30% in 2018.
Key disease/pt characteristics associated with the selection of regimens at 2L and 3L are summarized in the Table. Prior IMiD treatment limited the use of IMiD-based therapy in subsequent lines. The use of KRd, IRd and DRd was mostly associated with ISS stage III, while the use of KRd was less frequently reported in pts with cardiac comorbidities. In pts with prior PI treatment, KRd and IRd (but not Kd) were more common at 2L, while DRd was preferred at 3L. A higher proportion of fit, young, or prior-SCT pts were treated with KRd or DRd, while IRd was the preferred treatment in pts with biochemical relapse.
Conclusions
Multiple drug approvals for RRMM in Europe have resulted in marked changes in the treatment algorithm, with a more immediate impact in countries with earlier access to new treatment options. Multiple decision drivers such as age, fitness, comorbidities and prior treatment are associated with uptake of different novel regimens at 2L and 3L. The increasing range of treatment options has resulted in pts receiving more lines of therapy for RRMM, highlighting the need for cautious planning of treatment sequencing to optimize the use of available combinations according to pt characteristics and disease factors.
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Merz:Janssen: Other: Travel grants; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Abbvie: Other: Travel grants; Celgene: Other: Travel grants; Takeda Vertrieb GmbH: Other: Travel grants, Research Funding. Pérez:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees. Kolb:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: travel and registration for my participation to international medical congres (ASH). Symeonidis:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zomas:Takeda: Employment. Gonzalez:Takeda: Employment. Kellermann:Amgen: Research Funding; BMS: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Takeda: Research Funding. Goldschmidt:Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; John Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; ArtTempi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; Mundipharma: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product.
A nationwide, multi-institutional survey was performed in 2011 and 2015 to analyze routine practice for myeloma patients outside clinical trials in Germany. We contacted university hospitals, ...community hospitals, and office-based hematologists in order to enter clinical data from newly diagnosed and relapsed patients into an online platform. Complete datasets were available for 478 (2011) and 515 (2015) patients. While median age at diagnosis increased from 70 to 72 years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented with equal performance status (ECOG 0–1, 2011 66%; 2015 68%). Cytogenetic analysis was performed in 53% (2011) and 59% (2015). Patients ≥70 years, or patients with comorbidities who were no candidates for autologous transplantation (ASCT), were less frequently tested for cytogenetic abnormalities (
p
= 0.001, respectively). There were more candidates for ASCT ≥65 years in 2015 (57%) than in 2011 (27%). Bortezomib was used in 92% of transplant-eligible and 66% of transplant-ineligible patients as frontline therapy in 2015. Application of bortezomib and lenalidomide for the first relapse changed from 2011 (bortezomib 45%; lenalidomide 27%) to 2015 (bortezomib 28%; lenalidomide 54%). For the second relapse, application of lenalidomide decreased from 2011 (36%) to 2015 (23%). Pomalidomide entered treatment for the second relapse in 2015 (11% of patients). Taken together, we demonstrate that results from clinical trials are implemented into general practice in Germany.
Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients with a median age of >70 yrs. However, data on the management of these patients outside of clinical trials are scarce. ...To assess patterns of MDS management in routine patient care with regard to the impact of age, we conducted a multicenter, representative survey of MDS health services in Germany. Data of 269 patients treated at 57 institutions were collected from preplanned chart reviews and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index ≥ 3 according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis and International Prognostic Scoring System (IPSS) risk assessment were performed significantly less frequently in patients >75 yrs than in patients ≤75 yrs (P < 0.001 and P = 0.019). In bivariate analysis, potential predictors for performing IPSS risk assessment were age ≤75 yrs (y/n, P = 0.019), diagnosis at a university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients ≤75 yrs were more likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy, or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In bivariate analysis age ≤75 yrs (y/n, P = 0.007) was a significant predictor for active treatment with no correlation with the other predictors IPSS risk score int‐2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020). This survey confirms the impact of age on the thoroughness of MDS diagnosis and the decision for active treatment. As cytogenetic analysis and risk assessment are essential for the choice of appropriate therapy, elderly patients in particular may not be receiving adequate treatment.
The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term ...clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17 979 per QALY (€15 773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.
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