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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Philippe Moreau, Nantes Université
- Second opponent: Professor Sonja Zweegman, Amsterdam University Medical Center
- Third member and chair of the evaluation committee: Professor June Helen Myklebust, University of Oslo
Chair of the Defence
Professor Kjetil Taskén, University of Oslo
Principal Supervisor
MD, PhD Fredrik Schjesvold, Oslo University Hospital
Summary
Multiple myeloma primarily affects older adults, and early mortality remains a challenge. Advanced age, reduced performance status and renal impairment increase the risk of poor outcomes, yet patients with these characteristics are often excluded from clinical trials. This limits knowledge about how modern treatment strategies work in real world patient populations.
The aim of this thesis was to evaluate the efficacy and safety of treatment strategies in newly diagnosed multiple myeloma through prospective studies with broad eligibility criteria. The work focused on achieving minimal residual disease (MRD) negative complete response (CR), and on assessing whether deliberate dose adjustments could improve tolerability and outcomes in patient groups often underrepresented in clinical trials.
The thesis includes two clinical studies. The REST study included 51 transplant-ineligible patients (median age 77 years), without upper age limit or frailty exclusions. Patients received isatuximab, weekly bortezomib, lenalidomide and limited dexamethasone with modified dosing to reduce toxicity. MRD-negative CR was achieved in 37% of patients, with favorable safety and 78% progression-free survival at 18 months.
The REMNANT study included 382 transplant-eligible patients with broad inclusion criteria, including those with comorbidities and renal impairment. MRD-negative CR was achieved in 33% after consolidation, and outcomes were similar in patients ≥65 and <65 years. Higher-than-label lenalidomide dosing in patients with renal impairment was safe and resulted in renal responses in 77%, including 57% complete responses.
In conclusion, inclusive trial designs improve generalizability and access to treatment. Both studies demonstrated favorable efficacy and safety. The findings support adapted combination therapy in elderly and frail patients, confirm the benefit of high-dose therapy across age groups, and suggest that intensified lenalidomide dosing may enhance renal recovery.
Additional information
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