Patterns of previous and secondary malignancies in patients with multiple myeloma

Objectives: In contrast to secondary primary malignancies (SPM) following multiple myeloma (MM), less is known about previous malignancies. We therefore conducted a population-based study to assess the patterns of previous malignancies in MM patients as well as the risk for SPM. Methods: Using data from the Cancer Registry of Norway, we included 9574 MM patients and 37 810 matched control subjects. The association between previous malignancies and a subsequent diagnosis of MM was analysed by a logistic regression model and the risk for SPM by a Cox model. Results: A previous diagnosis of myeloproliferative neoplasia (MPN) (OR 3.57; 95% CI:1.45-8.80) and Hodgkin lymphoma (HL) (OR 3.66; 95% CI: 1.40-9.55) was associated with the subsequent development of MM. For MPN, the association with MM was explained by an excess of primary myelofibrosis (PMF) in the MM group. The overall incidence of a previous malignancy was not different between MM patients and the control subjects (OR 0.93; 95% CI: 0.87-1.00). MM patients had an increased risk for secondary acute myelogenous leukaemia/myelodysplastic syndromes (HR 6.1, 95% CI: 3.9-9.5). Conclusions: A previous diagnosis of HL and PMF was associated with a subsequent diagnosis of MM, whereas the overall incidence of previous cancers was not increased for MM patients

Incidence and survival of multiple myeloma: a population-based study of 10 524 patients diagnosed 1982–2017

Population‐based studies from high‐quality nationwide cancer registries provide an important alternative to clinical trials in the assessment of the impact of modern myeloma treatment. Based on data from the Cancer Registry of Norway, we investigated trends in incidence and relative survival (RS) for 10 524 patients in three age groups diagnosed between 1982 and 2017. Nationwide myeloma drug consumption statistics were obtained from the Norwegian Institute of Public Health. Patients aged <65 years had a steady increase in both 5‐ and 10‐year RS across all calendar periods from 1982. For patients aged 65–79 years, RS was stable until the calendar period 1998–2002, followed by an improvement in both 5‐ and 10‐year RS. The 5‐year RS for patients aged ≥80 years also increased significantly between the first and the last calendar period. In conclusion, we demonstrate a significant improvement in 5‐year RS in all age groups. Improved RS in patients aged ≥80 years at the time of diagnosis is only rarely described in other population‐based studies. For patients aged ≥65 years, the improvement in RS coincides with the introduction of modern drugs, whereas patients aged <65 years had an ongoing improvement before the introduction of autologous stem‐cell transplant

Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest

a b s t r a c t Background: The platelet inhibitor clopidogrel is administered to patients treated with therapeutic hypothermia following cardiac arrest due to acute coronary syndromes. Interactions with proton pump inhibitors and genetics are factors with a known potential to attenuate the platelet inhibition of clopidogrel. In patients treated with therapeutic hypothermia, reduced gastrointestinal function and hypothermia may also reduce the effect of clopidogrel. To investigate the net platelet inhibition of clopidogrel, we have measured the platelet reactivity index in patients treated with therapeutic hypothermia. Methods and results: Twenty-five Caucasian patients treated with clopidogrel and therapeutic hypothermia were prospectively included. Therapeutic hypothermia was defined as 33-34 • C and delivered for 24 h. Clopidogrel loading doses (300-600 mg) were administered enterally the day of admission and followed by 75 mg daily. Blood samples were collected on day 1 (n = 25) and day 3 (n = 16). The samples were analysed for inhibition by clopidogrel with a vasodilator stimulated phosphoprotein phosphorylation kit. On day 1 and day 3, platelet reactivity index was 0.77 ± 0.09 and 0.57 ± 0.16, respectively. The number of patients with a satisfactory antiplatelet effect (defined as platelet reactivity index &lt;0.5) were 0 (0%) and 5 (31%), respectively. Conclusion: In patients treated with therapeutic hypothermia after cardiac arrest, the effect of clopidogrel on platelets was virtually nonexistent on day 1 after administration, with some improvement on day 3

Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma:a randomized study

OBJECTIVES: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. METHODS: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. RESULTS: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. CONCLUSIONS: Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients