Search

Background: In the CONPET study, multiple myeloma patients with abnormal 18FDG positron emission/computed tomography scan after upfront autologous stem cell transplantation were treated with four cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Side effect registrations show that carfilzomib might cause dyspnea, cough, respiratory tract infections, and heart failure. The aims were to investigate patient-reported shortness of breath and dyspnea during KRd consolidation., Methods: To assess shortness of breath, patients completed the Functional Assessment of Cancer Therapy-Pulmonary Symptom Index (FACT-PSI) and the EORTC QLQ-C30 to assess dyspnea. Shortness of breath was defined as decrease in FACT-PSI score or starting/increasing diuretic drugs. Mixed effect logistic regression was used for the effect analysis. Linear mixed model and clinical relevance were used to investigate dyspnea., Results: A total of 50 patients were included, median age 62 years (interquartile range 54-67). 17% reported shortness of breath at Day 15 Cycles 1-4 versus 11% at Day 1 Cycles 2-4, Cycle 4 Day 29, and 1 month posttreatment (p-value 0.048). Compared with baseline, patients reported significant, and clinically relevant worsening in dyspnea during consolidation., Conclusion: Our study confirmed earlier findings of carfilzomib causing shortness of breath during KRd administration and revealed dyspnea during consolidation compared to baseline., Trial Registration: Clinicaltrials.gov: NCT03314636, EudraCT: 2017-000586-72., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Whole-body low-dose CT (WBLDCT) is recommended over classical skeletal surveys (CSS) for investigating bone disease in multiple myeloma (MM) based on retrospective studies. No prospective studies with serial follow-up scans exist., Objective: To compare WBLDCT to CSS for identifying progressive bone disease in MM in a prospective setting., Methods: Ninety-six patients with MM at Odense University Hospital and Stavanger Hospital were followed for up to four years. Patients were scanned with WBLDCT and CSS every year for the first two years and every six months thereafter or at suspicion of progression., Results: Nineteen cases of progressive bone disease were found using WBLDCT vs eight cases using CSS (p < 0.001). All cases of progressive bone disease using CSS were also identified by WBLDCT. Progression not found by CSS was primarily in the spine, sternum, and pelvis. Of the 19 cases, five patients had progressive bone disease only without other criteria for clinical progression. WBLDCT consistently identified more bone lesions per patient, 8.2 CI(6.8;9.6) vs CSS, 3.6 CI(2.7;4.5)., Conclusion: WBLDCT outperformed CSS for finding progressive bone disease and osteolytic lesions. More new lesions were found during follow-up by WBLDCT than CSS. Using CSS for lytic lesions will underestimate progression rates. Our data offer prospective evidence for the current recommendation using WBLDCT for skeletal evaluations in patients with multiple myeloma., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objective: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk cytogenetic abnormalities in lenalidomide-pretreated patients with multiple myeloma at first relapse., Methods: OPTIMISMM was a phase 3, multicenter, open-label, randomized study (NCT01734928; N = 559). The primary endpoint was progression-free survival (PFS)., Results: Overall, 226 patients had received one prior line of therapy. PVd significantly prolonged PFS vs Vd in patients aged ≤65 years (median, 22.0 vs 13.1 months; P = .0258) and >65 years (median, 17.6 vs 9.9 months; P = .0369). Median PFS in patients with renal impairment (RI; creatinine clearance <60 mL/min) was 15.1 months with PVd vs 9.5 months with Vd (hazard ratio [HR], 0.67 [95% CI, 0.34-1.34]). In patients without RI, median PFS was 22.0 vs 13.1 months (HR, 0.45 [95% CI, 0.27-0.76]). In patients with high-risk cytogenetics, median PFS was 14.7 vs 9.9 months (HR, 0.39 [95% CI, 0.13-1.17]). PVd significantly improved overall response rate vs Vd in all subgroups. The safety profile of PVd was consistent with previous reports., Conclusions: These findings confirmed the benefits of PVd at first relapse, including in patients with poor prognostic factors., (© 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objective: To evaluate changes in diagnostic and therapeutic approach in multiple myeloma among Norwegian hematologists in the current decade., Methods: This nationwide study in Norway is based on results of surveys conducted among professionally active hematologists from 2013 to 2019. Every year, respondents participating in the survey suggested treatment regimens used in typical clinical situations in patients with multiple myeloma, as well as diagnostic routines., Results: The use of regimens containing alkylators and thalidomide was common at the beginning of the studied period. Later, lenalidomide became the most preferred treatment in most first-line patients. Bortezomib maintained a stable position in the treatment of myeloma in patients with renal insufficiency. The lenalidomide, bortezomib, and dexamethasone combination became the preferred frontline triplet for transplant-ineligible patients and induction therapy before transplant. Nowadays, the relapse after lenalidomide-based treatment is managed using both bortezomib-based therapies and combinations with the newest agents. Together with the therapeutic landscape, the use of diagnostic criteria and workup as well as supportive care changed in the period influenced by local and international guidelines and recommendations., Conclusion: Norwegian hematologists gradually adopt new clinical concepts, guidelines, and recommendations in their practice., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited., Methods: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413)., Results: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma., Conclusions: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL., (© 2019 Takeda Pharmaceuticals. European Journal of Haematology published by John Wiley & Sons Ltd.)