CORRESPONDENCE

Tailored thromboprophylaxis for patients with multiple myelomatreated by IMIDs

SEMRA PAYDAS

Faculty of Medicine, Department of Oncology, Cukurova University, Adana, Turkey

(Received 2 April 2008; revised 3 May 2008; accepted 6 May 2008)

It is known that thrombo-embolic (TE) events are

one of the most important complications of immuno-

modulatory drugs used in multiple myeloma (MM).

For this reason, thrombo-prophylaxis is very impor-

tant according to the TE risk categories. I read with

great interest of the paper published by Niesvizky

et al. in this journal [1]. This study reported the use

of low-dose aspirin as primary prophylaxis in three

series of patients with MM treated by thalidomide or

lenalidomide containing regimens. In these studies

median age was at the beginning of the 60s and they

had good KPS (70 or higher). In study I, thalidomide

dose was 50–200 mg, dexamethasone dose was

40 mg once a week and chlarithromycin 500 mg

twice a day. Before the use of aspirin, grade II and

III–IV thrombosis developed in 8% and 15% of the

cases, respectively. TEs did not develop in subse-

quent cases receiving aspirin. In study II, thalido-

mide dose was 50–200 mg and dexamethasone dose

was standard (40 mg daily for 12 days in 1 month).

In this cohort, patients randomised into two groups

to receive either aspirin or not in conjunction with

thalidomide or chemotherapy alone. TE developed

in 21.4% of the cases not receiving aspirin and in 1 of

15 cases (6.6%) treated by aspirin. In study III,

patients received standard dose lenalidomide and

relatively low-dose dexamethasone (40 mg 6 days in

first cycle and then 4 days monthly) and daily

chlarithromycin and low-dose aspirin. TE occurred

in nine (12.5%) of the cases and five of these were

interrupted aspirin. Cases with TE were treated by

full-dose low-molecular weight heparin (LMWH) or

unfractionated heparin.

In this report, authors concluded that low-dose

aspirin appears to reduce the incidence of thrombo-

sis, and may be an adequate agent for prophylaxis,

except poor compliance, in cases treated by thalido-

mide or lenalidomide. However, two excellent re-

views were published recently [2,3], in one of them

[2] Niesvizky is one of the authors. In these reviews,

it has been proposed that:

1. The goal of thrombo-prophylaxis should be to

reduce the frequency of deep vein thrombosis to

less than 10%.

2. Thromboprophylaxis is strongly recommended

in cases receiving thalidomide combinations but

not thalidomide alone.

3. Thromboprophylaxis should be given according

to the presence of the risk factors which increase

the risk of TE. Risk factors associated with

patients are: age, obesity, co-morbid conditions

(including infection, diabetes mellitus, cardio-

vascular disease), surgical procedures, history of

TE or inherited thrombophilia, central venous

catheter. MM-related risk factors are MM

diagnosis, hyper-viscosity and high tumor bur-

den. Therapy-related risk factors are high-dose

dexamethasone, doxorubicin and multi-agent

chemotherapy.

According to these reviews, authors’ proposals are:

(1) There are no data to suggest that one antic-

oagulant is better than another. (2) Although aspirin

use is easy in daily practice, the rate of TE is relatively

high in particular conditions. (3) Until further

Correspondence: Semra Paydas, Faculty of Medicine, Dept of Oncology, Cukurova University, ADANA, Turkey. E-mail: sepay@cu.edu.tr

Leukemia & Lymphoma, August 2008; 49(8): 1644–1645

ISSN 1042-8194 print/ISSN 1029-2403 online � 2008 Informa UK Ltd.

DOI: 10.1080/10428190802187155

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evidence becomes available, aspirin should only be

recommended for patients with low risk of TE. (4)

Evidence of patients with high risk, supports the use

of LMWH or full-dose aspirin. (5) The use of

warfarin is limited due to its long half-life in patients

with concomitant thrombocytopenia. LMWH is

appropriate option because of its short half-life and

the decreased risk of secondary bleeding. Shortly,

panel recommends aspirin for patients with one risk

factor for TE and LMWH for cases with two or more

individual and/or MM risk factors. LMWH is

recommended for all patients receiving high-dose

dexamethasone or doxorubicin. Full-dose warfarin

targeting as therapeutic INR of 2–3 is an alternative

to LMWH although there are limited data in the

literature regarding this strategy.

As mentioned before, in studies reported by

Palumbo et al., [2,3] patients were relatively young

and had good PS. Also dexamethasone dose used

was relatively lower than standard high-dose regi-

mens, except cohort II. Although there are no data

about the co-morbid conditions and tumor burden,

these points are important due to the low-risk patient

characteristics in this article. In fact, as suggested by

the panel members, these patients are of low-risk

category and low-dose aspirin is enough for these

cases; however, it is not appropriate to recommend

low-dose aspirin for patients receiving thalidomide/

lenalidomide combinations without tailored

thrombo-prophylaxis.

Ongoing studies will determine what will be the

most appropriate TE prophylaxis in cases treated by

thalidomide/lenalidomide combinations in cases with

MM.

References

1. Niesvizky R, Martinez D, Jalbrzikowski J, Christos P, Furst J,

Sancho M, et al. Prophylactic low-dose aspirin is effective

antithrombotic therapy for combination treatments of thalido-

mide or lenalidomide in myeloma. Leuk Lymphoma 2007;

48:2330–2337.

2. Palumbo A, Facon T, Sonnoveld P, Blade J, Offidani M,

Gay F, et al. Thalidomide for treatment of multiple myeloma.

Blood. 2008;111:3968–3977.

3. Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG,

San Miguel J, Barlogie B, et al. Prevention of thalidomide- and

lenalidomide-associated thrombosis in myeloma. Leukemia

2008;22:414–423.

Correspondence 1645

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