Background: In multiple myeloma (MM), relapse is a problem after autologous hematopoietic stem cell transplantation (ASCT). In the nontransplant setting, thalidomide/dexamethasone/clarithromycin (BLT-D) and lenalidomide/dexamethasone/clarithromycin (BiRd) achieve responses with acceptable toxicity. Both regimens are reasonable objects of study in the post-ASCT setting. Patients and Methods: We report on BLT-D and BiRd given post-ASCT. Studies were conducted consecutively. After recovery from ASCT, therapy was started. All 3 drugs were given for 1 year, and then immunomodulatory drugs alone were given as long as tolerated or until disease progression. Results: For BLT-D, the most common toxicity was peripheral neuropathy (PN). For BiRd, infection, PN, and neutropenia were the most common adverse events. BiRd was associated with a higher frequency of secondary cancers. The median follow-up for BLT-D was 10.2 years (range 8.6-10.7) and for BiRd it was 7.5 years (range 6.4-8.4). After BLT-D, 18 patients (67%) were alive and 10 (37%) were alive without disease progression, and after BiRd, 18 patients (58%) were alive and 10 (32%) were alive without disease progression. Conclusions: BLT-D and BiRd can be given post-ASCT with different toxicity profiles and comparable disease-free and overall survival rates. A randomized study comparing these regimens to single-agent lenalidomide is needed to determine which approach is superior. Key Message: Relapse of MM is a major problem after ASCT. Strategies are needed post-ASCT to improve outcomes. In the nontransplant setting, thalidomide or lenalidomide/dexamethasone/clarithromycin treat MM with acceptable toxicity. We, thus, studied both regimens post- ASCT. They can be given with different toxicity profiles and result in good disease control.

1.
Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, Francois S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL: Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 2002;99:731-735.
2.
Vesole D, Crowley JJ, Catchatourian R, Stiff PJ, Johnson DB, Cromer J, Salmon SE, Barlogie B: High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial. J Clin Oncol 1999;17:2173-2179.
3.
Kapoor P, Kumar SK, Dispenzieri A, Lacy MQ, Buadi F, Dingli D, Russell SJ, Hayman SR, Witzig TE, Lust JA, Leung N, Lin Y, Zeldenrust SR, McCurdy A, Greipp PR, Kyle RA, Rajkumar SV, Gertz MA: Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. J Clin Oncol 2013;31:4529-4535.
4.
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C: Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1770-1781.
5.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL: Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1782-1791.
6.
Bjorkstrand B, Svensson H, Goldschmidt H, Ljungman P, Apperley J, Mandelli F, Marcus R, Boogaerts M, Alegre A, Remes K, Cornelissen JJ, Blade J, Lenhoff S, Iriondo A, Carlson K, Volin L, Littlewood T, Goldstone AH, San Miguel J, Schattenberg A, Gahrton G: Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2001;27:511-515.
7.
Cunningham D, Powles R, Malpas J, Raje N, Milan S, Viner C, Montes A, Hickish T, Nicolson M, Johnson P, Treleaven J, Raymond J, Gore M: A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol 1998;102:495-502.
8.
Geitz H, Handt S, Zwingenberger K: Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996;31:213-221.
9.
D'Amato RJ, Loughnan MS, Flynn E, Folkman J: Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994;91:4082-4085.
10.
Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G: Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991;173:699-703.
11.
Rowland TL, McHugh SM, Deighton J, Dearman RJ, Ewan PW, Kimber I: Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology 1998;40:11-20.
12.
D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS: Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma (review). Semin Oncol 2001;28:597-601.
13.
Haslett PA, Corral LG, Albert M, Kaplan G: Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998;187:1885-1892.
14.
McHugh SM, Rifkin IR, Deighton J, Wilson AB, Lachmann PJ, Lockwood CM, Ewan PW: The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 1995;99:160-167.
15.
Coleman M, Leonard J, Lyons L, Pekle K, Nahum K, Pearse R, Niesvizky R, Michaeli J: BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenstrom's macroglobulinemia. Leuk Lymphoma 2002;43:1777-1782.
16.
Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R: Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol 2010;85:664-669.
17.
Rossi A, Mark T, Jayabalan D, Christos P, Zafar F, Pekle K, Pearse R, Chen-Kiang S, Coleman M, Niesvizky R: BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma. Blood 2013;121:1982-1985.
18.
Crippa F, Holmberg L, Carter RA, Hooper H, Marr KA, Bensinger W, Chauncey T, Corey L, Boeckh M: Infectious complications after autologous CD34-selected peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2002;8:281-289.
19.
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481.
20.
Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J: Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006;354:1021-1030.
21.
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub AI, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T: Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006;108:3289-3294.
22.
Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N: Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009;27:1788-1793.
23.
Morgan GJ, Jackson GH, Davies FE, Drayson MT, Owen RG, Gregory WM, Cohen DC, Szubert AJ, Bell SE, Ross F, Child JA: Maintenance thalidomide may improve progression free but not overall survival: results from the myeloma IX maintenance randomisation. Blood 2008;112:656.
24.
Lokhorst HM, van der HB, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem BP, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P: A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood 2010;115:1113-1120.
25.
Barlogie B, Pineda-Roman M, van Rhee F, Haessler J, Anaissie E, Hollmig K, Alsayed Y, Waheed S, Petty N, Epstein J, Shaughnessy JD, Jr, Tricot G, Zangari M, Zeldis J, Barer S, Crowley J: Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 2008;112:3115-3121.
26.
Krishnan A, Pasquini MC, Ewell M, Stadtmauer EA, Alyea EP 3rd, Antin JH, Comenzo RL, Goodman S, Hari P, Negrin R, Qazilbash MH, Rowley SD, Sahebi F, Somlo G, Vesole DH, Vogl DT, Weisdorf DJ, Geller N, Horowitz MM, Giralt S, Maloney DG: Tandem autologous hematopoietic stem cell transplants (AuHCT) with or without maintenance therapy (auto-auto) versus single AuHCT followed by HLA matched sibling non-myeloablative allogeneic HCT (auto-allo) for patients with standard risk (SR) multiple myeloma (MM): results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 trial. Blood 2010;116:24-25.
27.
Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA: The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 2012;119:7-15.
28.
Ludwig H, Durie BG, McCarthy P, Palumbo A, San Miguel J, Barlogie B, Morgan G, Sonneveld P, Spencer A, Andersen KC, Facon T, Stewart KA, Einsele H, Mateos MV, Wijermans P, Waage A, Beksac M, Richardson PG, Hulin C, Niesvizky R, Lokhorst H, Landgren O, Bergsagel PL, Orlowski R, Hinke A, Cavo M, Attal M: IMWG consensus on maintenance therapy in multiple myeloma (review). Blood 2012;119:3003-3015.
29.
Hahn-Ast C, von Lilienfeld-Toal M, van Heteren P, Mückter S, Brossart P, Glasmacher A: Improved progression-free and overall survival with thalidomide maintenance therapy after autologous stem cell transplantation in multiple myeloma: a meta-analysis of five randomized trials. Haematologica 2011;96:367.
30.
Stewart AK, Trudel S, Bahlis NJ, White DJ, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Sussman J, Meyer RM, Harnett EL, Oana D, Chapman JA, Shepherd L: A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): the NCIC CTG MT.10 trial. Blood 2010;116:39.
31.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Facon T, Hulin C, Moreau P, Mathiot C, Roussel M, Payen C, Olivier P, Avet-Loiseau H: Lenalidomide maintenance after stem-cell transplantation for multiple myeloma: follow-up analysis of the IFM 2005-02 trial. Blood 2013;122:406.
32.
Gay F, Cavallo F, Caravita T, Cavalli M, Nagler A, Montefusco V, Pogliani EM, Buttignol S, Zamagni E, Palladino C, Marcatti M, Musto P, Catalano L, Baraldi A, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Vallone LM, Ciccone G, Ben Yehuda D, Di Raimondo F, Hardan I, Boccadoro M, Palumbo A: Maintenance therapy with lenalidomide significantly improved survival of young newly diagnosed multiple myeloma patients. Blood 2013;122:2089.
33.
Palumbo A, Bringhen S, Kumar SK, Lupparelli G, Usmani S, Waage A, Larocca A, van der Holt B, Musto P, Offidani M, Petrucci MT, Evangelista A, Zweegman S, Nooka AK, Spencer A, Dimopoulos MA, Hajek R, Cavo M, Richardson P, Lonial S, Ciccone G, Boccadoro M, Anderson K, Barlogie B, Sonneveld P, McCarthy PL: Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncol 2014;15:333-342.
34.
Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, Rajkumar SV: Melphalan, prednisone, and thalidomide vs. melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood 2015;126:1294-1301.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.