Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: Updated safety run-in results from the randomized phase 3 ithaca study

Background: Results from a randomized, Phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) previously showed that treatment with lenalidomide plus dexamethasone (Rd) may delay progression to active disease in patients (pts) with high-risk smoldering multiple myeloma (SMM), compared with observation. To further improve outcomes, addition of the anti-CD38 antibody isatuximab (Isa) to lenalidomide and dexamethasone (Isa-Rd) for the treatment of pts with high-risk SMM is being evaluated in the ongoing, randomized, multi-center, Phase 3 ITHACA study (NCT04270409). Initial findings from the safety run-in analysis of this trial have shown a manageable safety profile and encouraging, preliminary anti-myeloma activity. We now report updated safety and efficacy results from the safety run-in part of ITHACA at a median follow-up of 19.4 months. Methods: Pts were included in the study if they had been diagnosed within 5 years with SMM (per the International Myeloma Working Group [IMWG] criteria) and had high-risk SMM according to the Mayo '20-2-20' and/or updated PETHEMA model criteria. Pts who had received prior anti-myeloma treatment were not eligible. Enrolled pts received Isa 10 mg/kg IV on day (D) 1, 8, 15, and 22 in cycle (C) 1, D1 and D15 C2-12, D1 C13-36; plus R D1-21 (25 mg C1-9; 10 mg C10-24) and d weekly (40 mg, 20 mg for ≥75 yr-old pts C1-9; 20 mg C10-24). Cycle duration was 28 days. Safety evaluations included treatment-emergent AEs (TEAEs)/serious AEs and laboratory parameters, graded by NCI-CTCAE v5.0. Response was determined by IMWG criteria (2016). Mandatory imaging by MRI and/or low-dose whole-body CT/PET-CT, and assessments of minimal residual disease (MRD, by next-generation sequencing in pts with very good partial response [VGPR] or better), were performed at protocol-defined time points. The primary study objective for the safety run-in was to confirm the recommended dose of Isa in combination with Rd. Overall response rate (ORR) and MRD negativity rate at 10-5 sensitivity were included as secondary endpoints.Sanof

Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Objective: We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma.Methods: This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 -> 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86).Results: Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections.Conclusion: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.</p

SARS-CoV-2 infection in patients with multiple myeloma: survey in 23 centers across Europe and USA

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material and methods: We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease

Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group

Background: Decisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS). Methods: HRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P &lt; 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum. Results: 168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8–5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1–5.9). Conclusions: Kd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.</p

Pirmosios Baltijos šalyse taikomos robotinės chirurgijos sistemos „Versius“ daugiadisciplinis diegimas

On June, 2023, Vilnius University Hospital Santaros Klinikos started robotic-assisted operations using VERSIUS robotic surgery system (CMR, Cambridge, UK) and performed 29 robotic surgeries within the first 3 weeks. This surgical system was purchased with funding from the European Regional Development Fund. Comprehensive three-month-long learning courses were organized for a total number of 32 persons, forming 8 independent teams, each consisting of 2 surgeons and 2 nurses. Learning courses consisted of online theoretical training modules, a one-week learning course including technical skills training with a simulator and dry runs as well as cadaveric surgical cases. Furthermore, an additional learning module included dry runs in the operating room prior to the first surgeries, following live and online proctored surgical cases. This enabled a rapid and smooth introduction of the robotic surgical system into clinical practice without putting patients at risk. Abdominal surgeons, urologists, and gynecologists have already performed surgeries using the VERSIUS surgical system and no major complications have been reported. Thoracic surgeons are underway to begin thoracic robotic-assisted surgeries, completing the multidisciplinary VERSIUS surgical system implementation process. Our goal is to share initial experience with robotic VERSIUS surgical system and evaluate its implementation in Vilnius University Hospital Santaros Klinikos.2023 m. birželio mėn. Vilniaus universiteto ligoninėje Santaros klinikose pradėtos atlikti robotinės operacijos, naudojant robotinės chirurgijos sistemą „Versius“ (CMR, Kembridžas, JK). Per pirmąsias tris savaites atliktos 29 robotinės operacijos. Sistema įsigyta panaudojus Europos regioninės plėtros fondo lėšas. Išsamius 3 mėn. teorinius kursus išklausė ir praktiniuose mokymuose dalyvavo 32 Santaros klinikų medicinos darbuotojai. Jie suformavo 8 nepriklausomas komandas, sudarytas iš 2 chirurgų ir 2 slaugytojų. Mokymosi kursai apėmė: nuotolinius teorinio mokymo modulius; vienos savaitės mokymosi kursą, kurio metu lavinti techniniai įgūdžiai naudojant virtualiosios realybės simuliatorius; techninių įgūdžių mokymus, naudojant pilvo ertmės ir krūtinės ląstos ertmės operacijų muliažus; praktinius seminarus, per kuriuos buvo atliekamos operacijos, naudojant kadaverinius preparatus. Artėjant pirmosioms operacijoms, visos 8 komandos išėjo antrąjį mokymosi kursą operacinėje, naudodamiesi chirurginių įgūdžių lavinimo ir operacijų simuliavimo muliažais. Mokymų kursų pabaigoje atliktos kruopščiai suplanuotos pirmosios robotinės operacijos, dalyvaujant patyrusiems robotinės chirurgijos specialistams – mentoriams. Kruopštus standartizuotas mokymosi procesas leido greitai ir sklandžiai įdiegti robotinę chirurgiją į klinikinę praktiką, nekeliant pavojaus pacientams. Naudodami chirurginę sistemą „Versius“, pilvo chirurgai, urologai ir ginekologai jau atliko reikšmingą kiekį operacijų, išvengdami didelių komplikacijų. Pastaruoju metu pirmąsias operacijas atliko ir krūtinės chirurgai. Taip Vilniaus universiteto ligoninėje Santaros klinikose baigiamas robotinės chirurgijos sistemos „Versius“ daugiadisciplinio diegimo procesas. Straipsnio tikslas – pasidalyti pirmąja patirtimi, naudojant „Versius“ robotinės chirurgijos sistemą, ir įvertinti šios sistemos diegimo Vilniaus universiteto ligoninėje Santaros klinikose procesą

Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Objective We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 → 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4–21.8) in the control group (HR 0.46, 95% CI 0.30–0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity

Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma : A randomised phase 2 trial by the Nordic Myeloma Study Group

Objective We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 -&gt; 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity

Ixazomib, Lenalidomide, and Dexamethasone (IRD) Treatment with Cytogenetic Risk-Based Maintenance in Transplant-Eligible Myeloma: A Phase 2 Multicenter Study by the Nordic Myeloma Study Group

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib–lenalidomide–dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of −5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD −5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD −5. Altogether 95% of the patients with sustained MRD −5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients