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    Thalidomide in Patients With Multiple Myeloma and Renal Failure

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    Prasun Sit Sharma
    This document discusses the use of thalidomide in treating multiple myeloma patients with renal failure. It reports on the experiences of 7 patients with varying degrees of renal impairment who were treated with thalidomide. Plasma concentration measurements found thalidomide levels ranged from 0.39 to 1.48 ug/ml. Minor side effects like sedation and constipation occurred in most patients. More serious complications like neutropenia and thromboembolic events were not observed. However, hyperkalemia is a potential serious complication, as seen in one patient, and may occur early or later in treatment. The document concludes that thalidomide is generally a safe treatment for relapsed or refractory myeloma in patients with renal failure when

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    Thalidomide in Patients With Multiple Myeloma and Renal Failure

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    Prasun Sit Sharma
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    This document discusses the use of thalidomide in treating multiple myeloma patients with renal failure. It reports on the experiences of 7 patients with varying degrees of renal impairment who were treated with thalidomide. Plasma concentration measurements found thalidomide levels ranged from 0.39 to 1.48 ug/ml. Minor side effects like sedation and constipation occurred in most patients. More serious complications like neutropenia and thromboembolic events were not observed. However, hyperkalemia is a potential serious complication, as seen in one patient, and may occur early or later in treatment. The document concludes that thalidomide is generally a safe treatment for relapsed or refractory myeloma in patients with renal failure when

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    This document discusses the use of thalidomide in treating multiple myeloma patients with renal failure. It reports on the experiences of 7 patients with varying degrees of renal impairment who were treated with thalidomide. Plasma concentration measurements found thalidomide levels ranged from 0.39 to 1.48 ug/ml. Minor side effects like sedation and constipation occurred in most patients. More serious complications like neutropenia and thromboembolic events were not observed. However, hyperkalemia is a potential serious complication, as seen in one patient, and may occur early or later in treatment. The document concludes that thalidomide is generally a safe treatment for relapsed or refractory myeloma in patients with renal failure when

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    31 views2 pages

    Thalidomide in Patients With Multiple Myeloma and Renal Failure

    Uploaded by

    Prasun Sit Sharma
    This document discusses the use of thalidomide in treating multiple myeloma patients with renal failure. It reports on the experiences of 7 patients with varying degrees of renal impairment who were treated with thalidomide. Plasma concentration measurements found thalidomide levels ranged from 0.39 to 1.48 ug/ml. Minor side effects like sedation and constipation occurred in most patients. More serious complications like neutropenia and thromboembolic events were not observed. However, hyperkalemia is a potential serious complication, as seen in one patient, and may occur early or later in treatment. The document concludes that thalidomide is generally a safe treatment for relapsed or refractory myeloma in patients with renal failure when

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    of 2

    Correspondence

    drugs, leaving only a small proportion requiring systemic References


    treatment. Our own experience with rFVIIa and reports in the
    Almeida, A.M., Khair, K., Hann, I. & Liesner, R. (2003) The use of
    literature on the use of rFVIIa in treating this group of patients
    recombinant factor VIIa in children with inherited platelet function
    involve small numbers of patients. Systematic data collection disorders. British Journal of Haematology, 121, 477–481.
    as recommended by the international registry on rFVIIa and Poon, M.C. & d’Orion, R. (2000) Recombinant activated factor VII
    congenital platelet disorders group (Poon & d’Orion, 2000) are (NovoSeven) treatment of platelet-related bleeding disorders.
    therefore important in providing useful information on dosing International Registry on Recombinant Factor VIIa and Congenital
    regimes, efficiency and safety in these rare disorders. Platelet Disorders Group. Blood Coagulation Fibrinolysis, 11(Suppl.
    1), S55–S68.
    Mohamed Kaleelrahman1
    Adrian Minford2
    Keywords: recombinant factor VIIa, Bernard–Soulier syn-
    Liakat Ali Parapia1
    drome, Glanzmann’s thrombasthenia, congenital platelet func-
    1
    Haemophilia Centre, and 2Department of Paediatrics, Bradford tion disorders, platelet transfusion.
    Teaching Hospitals NHS Trust, Bradford, UK.
    doi:10.1111/j.1365-2141.2004.04878.x
    E-mail: parapia@doctors.org.uk

    Thalidomide in patients with multiple myeloma and renal


    failure

    Thalidomide, a derivate of glutamic acid, is increasingly used dialysis respectively. The thalidomide extraction coefficient
    in patients with multiple myeloma (MM) (Singhal et al, 1999). was 0Æ057 and the dialytic clearance was 1Æ73 ml/min.
    It has proved to be active in up to one-third of patients with Data regarding the pharmacokinetics of thalidomide are
    refractory or relapsing MM. Renal failure is a frequent particularly scarce due to the absence of a suitable intraven-
    complication of MM that is present in 50% of newly diagnosed ous formulation and the withdrawal of this drug from clinical
    patients (Kyle et al, 2003). Data regarding thalidomide phar- practice for several decades. To our knowledge, no pharma-
    macokinetics and tolerance in patients with renal failure are cokinetics data of thalidomide have been reported previously
    lacking. We report our early experience regarding the use of in patients with MM, either with or without renal failure.
    thalidomide in seven patients with MM and variable degrees of A trough plasma thalidomide level of 0Æ8–1Æ5 lg/ml is
    renal insufficiency. probably a suitable target in patients with MM who have renal
    Seven patients (three females and four males) diagnosed failure. However, there is no clear correlation between the dose
    with MM between 1996 and 2001 received treatment with of thalidomide, its plasma concentration and the clinical
    thalidomide (Laboratoire Laphal, Paris, France). Four patients response in patients with MM (Kumar et al, 2003). Thus,
    received a combination of steroids and thalidomide. lower trough levels (around 0Æ5 lg/ml), as in patients 3 and 7,
    The main characteristics of these patients before and during may be acceptable particularly in the maintenance phase of
    treatment are summarized in Table I. Patient 7 presented with thalidomide treatment.
    severe hyperkalaemia (>8 mmol/l) on two occasions during For plasma trough levels of 0Æ8–1Æ5 lg/ml, thalidomide
    therapy with 400 mg/d thalidomide. However, hyperkalaemia tolerance is fairly good in patients with renal failure. Minor
    recurred when the thalidomide dosage was tapered to 100 mg/d. thalidomide toxic effects, mainly sedation, constipation, and
    The measurement of thalidomide trough plasma concen- nausea, occur in virtually all treated patients and may subside
    tration using a high-performance liquid chromatography with time. Seven of eight patients in our series experienced
    method as described previously (Eriksson et al, 1992) was minor thalidomide toxicity. More serious complications such
    performed in each patient on one to four occasions. as neutropenia and thromboembolic events were not
    Thalidomide trough plasma level ranged from 0Æ39 lg/ml to observed in our patients. However, as recently reported
    1Æ48 lg/ml. Serial plasma thalidomide concentration measure- (Harris et al, 2003), hyperkalaemia is a specific and serious
    ments were performed in patient 2 during a haemodialysis potential complication of thalidomide in patients with renal
    session (DiCEA, Baxter, France; cellulosic membrane, surface failure. It usually occurs during the first few weeks of
    area ¼ 1Æ70 m2, ultrafiltration coefficient: 12Æ5). Serum treatment (as in patient 7) but may occur later during the
    thalidomide concentrations were 1Æ48 lg/ml at initiation of treatment with thalidomide. The mechanisms underlying the
    dialysis and 1Æ1, 0Æ96, 1Æ06 and 0Æ68 lg/ml at 1, 2, 3 and 4 h of thalidomide-associated hyperkalaemia remain unclear and

    96 ª 2004 Blackwell Publishing Ltd, British Journal of Haematology, 125, 90–102


    Correspondence

    Table I. Data regarding thalidomide use in seven patients with variable degrees of renal failure.

    TH measurement

    Immunological CrCl at the Starting dose of TH serum Impact of TH


    Patient Gender/age characteristics of start of TH TH/maximal TH dose CrCl concentration on MM (duration
    no. (years) serum (urine) (ml/min) dose of TH (mg/d) (mg/d) (ml/min) (lg/ml) of effect) Side-effects

    1 M/66 IgG k (BJP+) 47 100/300 300 54 0Æ81 PR (1 year)* Constipation


    300 55 0Æ85
    2 M/71 IgG j (BJP+) 14 100/200 100 13 0Æ81 CR (5 months) Sedation
    100 9 1Æ2
    100 HD 1Æ48
    3 M/77 IgG k AL 16 100/100 100 17 0Æ39 CR maintained Dizziness
    amyloidosis (8 months)
    4 F/65 IgA k (BJP+) 15 100/300 200 <10 0Æ89 MR (2 months)* Sedation
    5 M/64 IgG k (BJP+) 19 200/200 100 HD 1Æ19 MR (4 months) –
    6 F/59 IgG j (BJP+) 25 200/400 100 10 1Æ21 MR (5 months) Peripheral
    neuropathy
    7 F/57 Light chain j HD 200/400 200 HD 1Æ2/0Æ4 CR Severe
    400 HD 2Æ1 Regression hyperkalaemia
    100 HD 0Æ5 of plasmocytosis Sedation
    100 HD 0Æ5 (5 months)* Myalgia
    Peripheral
    neuropathy

    BJP, Bence–Jones protein; TH, thalidomide; CrCl, creatinine clearance; MM, multiple myeloma; HD, haemodialysis; CR, complete remission; PR,
    partial response; MR, minor response.
    *Died.
    Complete haematological response was defined by the disappearance or a decrease >90% in the serum and/or urine monoclonal component.
    Partial and minor response were defined by a decrease of 50–90% and 25–49% in the serum and/or urine monoclonal component respectively.

    may be related to the lysis of MM cells or an extracellular chromatography: avoiding hydrolytic degradation. Journal of Chro-
    shift of potassium. matography, 582, 211–216.
    In conclusion, thalidomide is, in general, a safe treatment for Harris, E., Behrens, J., Samson, D., Rahemtulla, A., Russell, N.H. &
    relapsing or refractory myeloma in patients with renal failure. Byrne, J.L. (2003) Use of thalidomide in patients with myeloma and
    renal failure may be associated with unexplained hyperkalaemia.
    However, clinicians must be aware of the risk of severe
    British Journal of Haematology, 122, 160–161.
    thalidomide-associated hyperkalaemia, especially in haemo-
    Kumar, S., Gertz, M.A., Dispenzieri, A., Lacy, M.Q., Geyer, S.M.,
    dialysed patients. Iturria, N.L., Fonseca, R., Hayman, S.R., Lust, J.A., Kyle, R.A.,
    Fadi Fakhouri1 Greipp, P.R., Witzig, T.E. & Rajkumar, S.V. (2003) Response rate,
    Houda Guerraoui1 durability of response, and survival after thalidomide therapy for
    relapsed multiple myeloma. Mayo Clinic Proceedings, 78, 34–39.
    Claire Presne2
    Kyle, R.A., Gertz, M.A., Witzig, T.E., Lust, J.A., Lacy, M.Q., Dispen-
    Julie Peltier1
    zieri, A., Fonseca, R., Rajkumar, S.V., Offord, J.R., Larson, D.R.,
    Richard Delarue3 Plevak, M.E., Therneau, T.M. & Greipp, P.R. (2003) Review of 1027
    Patrice Muret4 patients with newly diagnosed multiple myeloma. Mayo Clinic
    Bertrand Knebelmann1 Proceedings, 78, 21–33.
    1 Singhal, S., Mehta, J., Desikan, R., Ayers, D., Roberson, P.,
    Service de néphrologie, AP-HP, Hôpital Necker, Paris, 2Service de
    Eddlemon, P., Munshi, N., Anaissie, E., Wilson, C., Dhodapkar, M.,
    néphrologie, Hôpital Sud, Amiens, 3Service d’hématologie, Hôpital
    Zeddis, J. & Barlogie, B. (1999) Antitumor activity of thalidomide in
    Necker, Paris, and 4Service de pharmacologie, Hôpital Jean Minjoz,
    refractory multiple myeloma. The New England Journal of Medicine,
    Besançon, France. E-mail: fadi.fakhouri@nck.ap-hop-paris.fr 341, 1565–1571.

    References Keywords: thalidomide, multiple myeloma, pharmacokinetics,


    renal failure.
    Eriksson, T., Bjorkman, S., Fyge, A. & Ekberg, H. (1992) Determina-
    tion of thalidomide in plasma and blood by high-performance liquid doi:10.1111/j.1365-2141.2004.04875.x

    ª 2004 Blackwell Publishing Ltd, British Journal of Haematology, 125, 90–102 97

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