Thrombosis is associated with inferior survival in multiple myeloma

Kristinsson, Sigurður Y.; Pfeiffer, Ruth M.; Björkholm, Magnus; Schulman, Sam; Landgren, Ola

doi:10.3324/haematol.2012.064444

Cited by 73 publications

(64 citation statements)

References 24 publications

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“…In patients receiving LEN + DEX, thrombotic events occurred even at the rate of 30%, ischemic strokes and myocardial infarctions, as arterial thromboembolic manifestations, were also observed [4,22].…”

Section: Discussionmentioning

confidence: 89%

“…In the above mentioned group, following treatment was most frequently used: bortezomib (22) or thalidomide (20), or bendamustine (10), and less frequently VAD (4 patients), CVMBP 8 patients, MP (6 subjects), EDAP (etoposide + dexamethasone + cytarabine G-CSF) 5 subjects, steroid pulses 3 patients, radiotherapy 3 patients or were qualified Table 6 Cause of deaths in patients treated with lenalidomide (by incidence). to clinical trials (10 subjects).…”

Section: Follow-up Periodmentioning

confidence: 98%

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Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

et al. 2016

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Section: Discussionmentioning

confidence: 89%

Section: Follow-up Periodmentioning

confidence: 98%

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

et al. 2016

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“…There is suggestion that VTE has no impact on survival of myeloma patients in the first 6 months of diagnosis. Only arterial thrombosis which was seen in 5.6% of MM patients was associated with inferior survival [16]. However the early survival deficit seen in a trial of high dose dexamethasone and iMiD compared to the low dose dexamethasone iMiD arm (despite a much improved response rate in the high dose arm) did raise concerns that some of these patients may have experienced undiagnosed lethal VTE [17,18].…”

Section: Editorialmentioning

confidence: 87%

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Maraveyas¹

2015

Pancreat Disord Ther

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EditorialHypercoagulability and the clinical manifestation of VTE are shared by most cancers and the use of chemotherapy canfurther increase this risk. VTE in cancer patients results in increased morbidity and mortality [1]. Patients with advanced pancreatic cancer (APC) have one of the worst prognoses of all malignancies and the highest incidence of disease provoked venous thromboembolism (VTE) [2]. Given the prominence of VTE in APC, it is not surprising that data on VTE prevention for APC have been generated from subgroup analysis of non-APC targeted placebo-controlled randomized trials of cancer patients treated with chemotherapy. Further data is derived from trials dedicated to evaluate VTE prophylaxis in APC patients. These studies have been rather homogeneous in that only low molecular weight heparins (LMWH) have been investigated for anticoagulation. The choice of LMWH was partly industry driven (e.g. study of new agent such as the semi-synthetic LMWH semuloparin) and partly due to the established superiority of LMWH over vitamin K analogues in terms of safety and efficacy both in VTE prophylaxis when given in nononcologic settings and in the therapeutic (treatment) settings of malignancy associated established VTE [3]. SAVE-ONCO and PROTECHT are the largest trials that enrolled between them more than 4000 patients with non-selected solid cancers using LMWH for the variable length of palliative chemotherapy. Both studies showed similar reduction in the symptomatic venous thrombosis (DVT) and non-fatal pulmonary embolism (PE) and in the case of SAVE-ONO, arterial thromboemoblic events were also decreased. There was a subgroup of around 300 APC patients in both of these trials but benefit in APC subgroup was only seen in SAVE-ONCO study. While the VTE reduction for the whole patient population (primary aim of the study) was from 3.9% to 2%, it went from 10.9% in the placebo arm to 2.4% in the LMWH arm for the APC subgroup [4,5]. Two trials evaluated VTE prevention by enrolling APC patients only who were receiving gemcitabine based first line palliative chemotherapies. These studies randomized over 400 APC patients equally into LMWH or placebo. CONKO 004 showed that the use of enoxaparin at an unconventionally (high) primary prophylaxis dose of 1 mg/kg reduced the incidence of symptomatic (DVT and PE combined) from 9.87 to 1.25% [6]. FRAGEM had a broader primary endpoint of all-type VTE (i.e.DVT/PE but also incidental PE and arterial and splanchnic VTE), [2] and an "even higher" dose of LMWH (dalteparin at 150-200 u/kg) was used. It showed a significant 85% risk reduction in all-type VTE in the dalteparin arm as compared to placebo (3.4% vs. 23%) over the 3 months of thromboprophylaxis [7]. None of these studies increased risk of major bleeding significantly and no fatalities were noted in APC due to haemorrhage in either of these RCTs. Subsequent meta-analysis of these trials have verified the significant impact of thromboprophylaxis on APC related VTE [1].Up to a quarter of APC patients die within the fir...

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“…The interaction between cancer cells and coagulation has been known for many years [2,12,20,21]. While cancer cells trigger coagulation and cause an increased incidence of VTE, cancer progression is facilitated by blood coagulation.…”

Section: Discussionmentioning

confidence: 99%

Does Low-Molecular-Weight Heparin Influence the Antimyeloma Effects of Thalidomide? A Retrospective Analysis of Data from the GIMEMA, Nordic and Turkish Myeloma Study Groups

et al. 2015

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Background/Aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dellʼAdulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study.

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Thrombosis is associated with inferior survival in multiple myeloma

Cited by 73 publications

References 24 publications

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Does Low-Molecular-Weight Heparin Influence the Antimyeloma Effects of Thalidomide? A Retrospective Analysis of Data from the GIMEMA, Nordic and Turkish Myeloma Study Groups

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Thrombosis is associated with inferior survival in multiple myeloma

Cited by 73 publications

References 24 publications

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Does Low-Molecular-Weight Heparin Influence the Antimyeloma Effects of Thalidomide? A Retrospective Analysis of Data from the GIMEMA, Nordic and Turkish Myeloma Study Groups

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Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?