ABSTRACT
Background: High-risk smoldering multiple myeloma (HR-SMM) is associated with a greater risk of progression to symptomatic disease, suggesting the need for early, efficacious therapeutic interventions to improve outcomes. The ongoing, randomized Phase 3 ITHACA study (NCT04270409) is evaluating efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with lenalidomide (R) and dexamethasone (d) (Isa-Rd) vs Rd in patients (pts) with HR-SMM. We report here preliminary results from the safety run-in part of this trial. Methods: The primary objective was to confirm the recommended dose of Isa in combination with Rd. Pts were eligible if diagnosed with SMM within 5 years and HR-SMM defined by the Mayo ‘20-2-20’ and/or updated PETHEMA model criteria. Minimal residual disease and imaging by MRI and low-dose whole-body CT/PET-CT will be assessed at fixed time points. Results: As of April 12, 2021, 23 pts (median age, 63 [28–85] years;median time from initial diagnosis, 1.14 [0.1–5.2] years) had received Isa 10 mg/kg once weekly then biweekly (QW-Q2W) in combination with Rd. The median number of cycles was 7 (range, 4–10) and median duration of treatment exposure was 29.7 (range, 16.0–38.0) weeks. Two pts met the Mayo clinical model criteria, 13 pts the PETHEMA model criteria, and 8 pts both models’ criteria for HR-SMM. No pt presented with focal lesions at baseline. Seven (30.4%) pts developed 8 grade ≥3 non-hematologic treatment-emergent adverse events (TEAEs): COVID-19 pneumonia, insomnia (2 each), papular rash, muscle spasm, retinal detachment and hyperglycemia (1 each);no pt experienced a grade 5 TEAE and no pt discontinued treatment due to a TEAE. Serious TEAEs were COVID-19 pneumonia (n=2, grade ≥3) and pneumonia, musculoskeletal chest pain and pyrexia (n=1 each, grade <3). The most common, mostly grade 1–2 TEAEs were insomnia (39%) and constipation, headache, and peripheral edema (22% each). Infusion reactions were reported in 2 pts (8.7%) (grade 2, infusion day 1/cycle 1). By laboratory results, no grade 3–4 anemia or thrombocytopenia was observed;grade 3 neutropenia was reported in 5 pts (21.7%), with no grade 4. Isa exposure and CD38 receptor occupancy were in accordance with other MM studies, reaching target saturation in bone marrow plasma cells. The overall response rate was 86.9%;21.7%, 17.4%, and 4.3% of pts have so far achieved very good partial response (VGPR), complete response (CR) and stringent CR (sCR), respectively. Conclusions: Addition of Isa 10 mg/kg QW-Q2W to Rd was associated with a favorable safety profile in pts with HR-SMM, which compares well with Rd literature data in the same patient population. Isa-Rd has shown encouraging preliminary efficacy (21.7% sCR/CR and 43.4% ≥VGPR rates) in pts with HR-SMM. These results confirm the recommended dose of Isa for the randomized part of the Phase 3 ITHACA study, which will further evaluate efficacy and safety of Isa-Rd in HR-SMM. Funding: Sanofi.
ABSTRACT
The new pandemic disease Covid-19 compelled all the researchers to investigate for early identification of the potential risk factors. Further, the relation between smoking and infections are well known. The authors are trying to find the epidemiological links, the pathogenic mechanisms and also the impact of this coronavirus on different respiratory chronic diseases, based on the last published data about the consequences of smoking and vaping on consumers. © 2020 Florin MihÄltąn et al., published by Sciendo 2020 O nouÄ boalÄ pandemicÄ a obligat toÈi cercetÄtorii sÄ cerceteze pentru identificarea timpurie a factorilor de risc potenţiali. Conexiunile fumatului la infecÈii sunt bine cunoscute. Autorii încearcÄ sÄ vadÄ care sunt legÄturile epidemiologice, mecanismele patogenice Èi, de asemenea, impactul acestui coronavirus asupra diferitelor boli cronice respiratorii, cÄutând ultimele date publicate despre consecinÈele fumatului Èi "vapingului"asupra consumatorilor.