Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January ...2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.
Objective
We describe real‐world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM).
Method
First ...line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005–2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse.
Results
We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high‐risk MM in a real‐ world‐population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches.
Conclusion
National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.
Abstract
Pomalidomide‐dexamethasone (Pd) has been a standard care treatment for relapsed and refractory multiple myeloma since 2013. However, the outcomes of Pd after exposure to CD38 antibodies are ...not known. Here we describe the real‐world use and efficacy of pomalidomide in a Danish, nationwide cohort of daratumumab‐exposed patients. We identified 328 patients that were treated with pomalidomide. Of these, 137 received Pd, 65 daratumumab‐pomalidomide‐dexamethasone (DPd), 43 pomalidomide‐cyclophosphamide‐dexamethasone (PCd), 19 carfilzomib‐pomalidomide‐dexamethasone (KPD), 11 pomalidomide‐bortezomib‐dexamethasone (PVd), and 52 pomalidomide in other combinations. Patients treated with Pd in this cohort had a partial response or better (≥ PR) rate of 35.8% and median time to next treatment (mTNT) of 4.9 months, almost identical to the results of previous prospective clinical trials. Although treatment with the various pomalidomide‐containing triplet regimens resulted in higher ≥ PR rates (PCd: 46.5%, PVd: 63.6%, DPd: 55.4%, KPd: 63.2%), the mTNT achieved was not significantly better than with Pd in most cases (PCD: 5.4, PVD: 5.3, DPD: 4.7 months). The exception to this was KPd (mTNT 7.4 months), but this regimen was mainly used earlier in the course of the disease (median time from diagnosis 2.3 years vs. 3.7–4.3 years). The most important predictor of outcomes was not the choice of index regimen (
p
= 0.72), but prior exposure (
p
= 0.0116). Compared to CD38 antibody‐naïve patients, triple‐class‐exposed patients achieved reduced ≥ PR rate (38.0% vs. 47.3%), shorter mTNT (4.0 vs. 5.9 months), and shorter median overall survival (12.4 vs. 24.2 months) with pomalidomide treatment.
Lenalidomide maintenance (LM) has shown benefit in progression‐free survival (PFS) and overall survival (OS) in clinical trials. LM is the recommended standard of care in patients with newly ...diagnosed multiple myeloma (MM) after high‐dose melphalan and autologous stem cell transplantation (HDM‐ASCT). In Denmark, LM has been approved and publicly funded for all patients treated with HDM‐ASCT since June 2019. Patients with newly diagnosed MM treated with their first HDM‐ASCT between June 2019 and March 2022 were included and followed until data cut‐off in June 2023. To compare outcomes, a historical pre‐LM cohort from the Danish MM Registry, consisting of 364 MM patients treated with HDM‐ASCT between June 2015 and June 2019, was used. Among 364 patients treated with HDM‐ASCT after June 2019, 22.3% received consolidation therapy and 3.7% underwent tandem HDM‐ASCT. During follow‐up, 297 patients (81.6%) initiated maintenance therapy, with 277 (76.1%) receiving LM. Overall, 145 patients (52.3%) discontinued LM most commonly due to toxicity 75 (51.7%), with fatigue (30.7%), cytopenia (25.3%), and neuropathy (17.3%) being the main reasons. In a 6‐month landmark analysis, early discontinuation did not negatively impact PFS or OS. The LM cohort had similar PFS, and OS compared to the pre‐LM cohort. The 3‐year PFS and OS rates in the LM cohort were 61% and 86%, respectively, while the pre‐LM cohort had a 3‐year PFS of 55% and a 3‐year OS of 89%. In conclusion, the introduction of LM as a nationwide treatment option in Denmark did not lead to improved clinical outcomes.
In this retrospective study we reviewed the clinical course of every patient with multiple myeloma treated from 2006 to 2016 at Vejle Hospital: 303 patients with a median age of 69 years at diagnosis ...received a median of four (range 1–18) lines of therapy; 149 in a 2006–2010 cohort and 154 in a 2011–2016 cohort. After initiation of treatment, the median decrease in the number of patients per each subsequent line of therapy was 22%. Lenalidomide-dexamethasone (
n
= 156), bortezomib-dexamethasone (
n
= 107), and bortezomib-lenalidomide-dexamethasone (
n
= 84) were the most commonly used regimens. The partial response or better rate was 78%, 58%, 55%, and 44% in lines of therapy one to four, respectively. The median (95% confidence interval CI) progression-free survival was 18 (15–22), 10 (8–13), 8 (7–10), and 6 (4–8) months in lines of therapy one to four, respectively. The median (95% CI) overall survival (OS) was 4.1 (3.7–4.8) years. Compared with the 2006–2010 cohort, patients in the 2011– 2016 cohort had longer OS; 5.3 (4.7 to not reached)
versus
3.4 (2.7–4.0) years,
p
< 0.0001. This was especially true in patients not treated with high-dose therapy and autologous stem cell transplantation; 4.7 (3.2–5.9)
versus
2.6 (2.0–3.3) years,
p
= 0.0052. Patients in the 2011–2016 cohort were on treatment during a greater part of their life and had higher exposure to high-dose melphalan with autologous stem cell transplantation, lenalidomide, pomalidomide, daratumumab, and carfilzomib.
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