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of consistently negative survival data that is no
t reported on lenalidomide and pomalidomide in elderly patients. The result is that prescribers are putting their patients at risk and that patients are running a risk they are not aware of, even though it is known to the authorities, the authors state. “This has previously been overlooked, as these registration studies do not isolate the effect of the drugs on survival. In all three studies, more pre-specified high-dose dexamethasone is given to the control groups. Study E4A03 showed that high-dose dexamethasone renders significantly worse observed survival than low-dose dexamethasone together with lenalidomide,” stated Lindberg and Sjöberg in Läkartidningen. Note: Oncopeptides, where Lindberg is the former CSO and CEO, has developed a drug for the treatment of myeloma that is approved by the EMA and can be seen as a competitor to IMiDs. Per Sjöberg has worked as a consultant for Oncopeptides and holds shares in Oncopeptides. Q&A: Fredrik Schjesvold Fredrik Schjesvold, MD, PhD, founder and leader of Oslo Myeloma Center, Oslo University Hospital, and Leader of the Clinical Trial task force at the Nordic Myeloma Study Group. Describe the benefits of IMiDs for myeloma patients? “Early on, IMiDs showed an overall survival benefit over standard-of-care therapy. The overall survival benefit of lenalidomide addition to dexamethasone in relapsed myeloma led to the approval of lenalidomide in relapse, and to lenalidomide being the backbone of new relapse regimens. In newly diagnosed elderly people, the overall survival benefit of thalidomide addition to melphalan and prednisolone led to the approval of MPT (melphalan prednisolone thalidomide) in first-line treatment for the elderly. Later, lenalidomide-dexametason (Rd) demonstrated an overall survival benefit over MPT, and after that, daratumumab addition to Rd gave an overall survival benefit, and is now the standard of care. Overall survival has thus increased from around two years to around six to seven years for the elderly, to a large extent based on the impact of IMiDs. First-line treatments without lenalidomide have lower survival rates. Qualityof-life (QOL) is a more complicated issue. IMiDs have side effects, as do other drugs, but in the large majority of patients they are manageable, and in addition to the efficacy of the regimens this is good for the general QOL of patients, as far as I can understand the data.” Describe the disadvantages of IMiDs for myeloma patients? “Lenalidomide is by far the most used IMiD, and thus the most important one. The most problematic disadvantage is that fatigue is not uncommon, nor is gastrointestinal toxicity. If patients suffer from these problems, they should reduce the dose of their lenalidomide treatment, in collaboration with the treating doctor.” In your own studies and projects, have you investigated IMiDs, and if so, what have you focused on and found? “I have been the national coordinator or sponsor in 32 trials containing IMiDs (or CelMods, the next generation IMiDs). In most of these, IMiDs have been part of standard-of-care, the control arm, or part of the backbone of a new regimen. Two trials have investigated the addition of IMiDs or CelMods, one is the Optimismm trial with the addition of pomalidomide to bortezomibdex, and the other is Successor-2, which adds mezigdomide to carfilzomibdex. The Optimismm showed PFS benefit, leading to the approval of this combination, while the Successor-2 is not mature yet.” “I also participated in two trials where pomalidomide was challenged head-tohead, one with melflufen and one with ixazomib. Both trials showed equal survival. FA C T S IMIDS Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, antiinflammatory, and anti-proliferative effects. Multiple myeloma (myeloma) Multiple myeloma is a hematological cancer caused by a proliferation of clonal plasma cells, leading to anemia, renal failure, hypercalcemia, and destructive bone lesions resulting in significant morbidity. My opinion based on all of this is that IMiDs retain their place in standard-of-care.” In your opinion, based on the data that the authors of the op-ed article in Läkartidningen refer to, should treatment plans be adjusted for elderly myeloma patients or do you think other measurements should be taken? “I don't agree that there has been unexpectedly low improvements in the survival of elderly patients. In Norway (Cancer Registry reports), five-year relative survival in 2018 was 35.1% for patients of 71-90 years of age; in 2023 this was 54.8%, which is more than a 50% increase on a population-based level. This broadly coincides with lenalidomide becoming standard first-line treatment for elderly patients in Norway from 2016. Daratumumab-Rd is the standard-of-care in Norway today, which I think is justified by the data and the increase in survival for these patients in Norway.” When it comes to future treatments of myeloma patients, what are your hopes and expectations? Is there a particular new treatment or therapy that you believe will have clinical benefit for these patients? “There are many new treatments coming, but the most impactful will be the immunotherapies; CAR-Ts and bispecific antibodies. They are gradually being reimbursed in the Scandinavian countries. Approvals are in late line, but studies are ongoing in the early lines of treatment.” “We have eight studies in Norway where these therapies are being given in 1st or 2nd line, both for younger and elderly patients. My expectation is that a significant portion of patients in these trials will be cured, in the sense that they won't relapse within their life-time.” NLS NORDICLIFESCIENCE.ORG | 15