Cancer Treatment Today » Waldenstrom’s

PET for Waldenstrom – pro

M Levin, MD — Mon, 10 Sep 2012 20:59:21 +0000

Waldenstrom’s (WM)is an uncommon lymphoproliferative disorder characterized primarily by bone marrow infiltration and IgM monoclonal gammopathy. It should be considered a distinct clinicopathological entity rather than a clinical syndrome secondary to IgM secretion. Waldenström macroglobulinemia is a clonal disorder of B lymphocytes. This condition is considered to be lymphoplasmacytic lymphoma as defined by the Revised European American Lymphoma Classification (REAL) and World Health Organization (WHO) classification.

There is no literature on the usefullness of PET
for this disease, except a recent abstract, that concluded: “Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans, with the majority showing negative disease after therapy. This correlates with the 67.9% response rate. Positive PET images were inversely correlated to IgM level and directly related to elevated Beta-2 microglobulin and age. Significantly PET positive individuals may demonstrate a poorer prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM.”

Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, Morra E, Pangalis GA, San Miguel JF, Branagan AR, Dimopoulos MA.
Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia.Semin Oncol. 2003 Apr;30(2):110-5.

Dimopoulos MA, Panayiotidis P, Moulopoulos LA, et al: Waldenstrom’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol 2000 Jan; 18(1): 214-26

Dimopoulos MA, Galani E, Matsouka C: Waldenstrom’s macroglobulinemia. Hematol Oncol Clin North Am 1999 Dec; 13(6): 1351-66

B. Harris, X. Leleu, R. Leduc, D. Yarar, A. Sam, M. Rourke, S. Chuma, A. Roccaro, I. J Clin Oncol 27, 2009 (suppl; abstr e19518)
Diagnostic and prognostic use of FDG-PET scans in Waldenstrom’s macroglobulinemia. Print this page

Is Waldenstrom’s a “cancer”? – pro

M Levin, MD — Wed, 05 Sep 2012 23:15:28 +0000

Waldenstrom’s (WM) should be considered cancer since it is a presentation of a lymphoma. WM is an uncommon lymphoproliferative disorder characterized primarily by bone marrow infiltration and IgM monoclonal gammopathy. It should be considered a distinct clinicopathological entity rather than a clinical syndrome secondary to IgM secretion. Waldenström macroglobulinemia is a clonal disorder of B lymphocytes. This condition is considered to be lymphoplasmacytic lymphoma as defined by the Revised European American Lymphoma Classification (REAL) and World Health Organization (WHO) classification. The concentration of monoclonal IgM can vary widely in WM and it is not possible to define a concentration that reliably distinguishes WM from monoclonal gammopathy of undetermined significance (MGUS) and other lymphoproliferative disorders. A diagnosis of WM can therefore be made irrespective of IgM concentration if there is evidence on a bone marrow trephine biopsy of bone marrow infiltration by lymphoplasmacytic lymphoma with predominantly an intertrabecular pattern, supported by appropriate immunophenotypic studies.

Dimopoulos MA, Panayiotidis P, Moulopoulos LA, et al: Waldenstrom’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol 2000 Jan; 18(1): 214-26

Dimopoulos MA, Galani E, Matsouka C: Waldenstrom’s macroglobulinemia. Hematol Oncol Clin North Am 1999 Dec; 13(6): 1351-66

Rituxan for Waldenstrom’s macroglobulinemia – pro

M Levin, MD — Sat, 01 Sep 2012 20:45:21 +0000

Waldenström’s macroglobulinemia (WM) is a CD20 expressing B-cell malignancy represented by the pathological diagnosis of IgM secreting lymphoplasmacytic lymphoma. Since 1999, there have been many reprts and several phase II studies of Rituxan in this disease. Major response rates of 30% have been reported in most studies with standard dose rituximab, i.e. 4 weekly infusions at 375 mg/m2/week. A recent guideline states: “Rituximab is active in the treatment of WM but associated with the risk of transient exacerbation of clinical effects of the disease and should only be used with caution especially in patients with symptoms of hyperviscosity and/or IgM levels > 40g/L. Level of evidence IIb, Grade of recommendation B.” In light of this guidelien, Rituxan should not be considered experiemntal since it is recognized by exp[ert opinon to be useful in the form of the guideline.

A. Vijay and M. A. Gertz
Waldenstrom macroglobulinemia
Blood, June 15, 2007; 109(12): 5096 - 5103.

S. P. Treon, C. Emmanouilides, E. Kimby, A. Kelliher, F. Preffer, A. R. Branagan, K. C. Anderson, S. R. Frankel, and On behalf the Waldenstrom's Macroglobulinemia Clin
Extended rituximab therapy in Waldenstrom's macroglobulinemia
Ann. Onc., January 1, 2005; 16(1): 132 - 138.

J. Boye, T. Elter, and A. Engert
An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab
Ann. Onc., April 1, 2003; 14(4): 520 - 535.

Johnson SA, Birchall J, Luckie C, Oscier DG, Owen RG, Haemato-Oncology Task Force of the British Committee for Standards in Haematology. Guidelines on the management of Waldenstrom macroglobulinaemia. Br J Haematol 2006 Mar;132(6):683-97. [108 references]

Velcade for Waldenstrom’s – pro

M Levin, MD — Sat, 01 Sep 2012 20:12:22 +0000

Waldenström’s macroglobulinemia (WM) is a CD20 expressing B-cell malignancy represented by the pathological diagnosis of IgM secreting lymphoplasmacytic lymphoma.

Chen, et al. (2007) found bortezomib to be an active agent in Waldenstrom’s macroglobulinemia but it was an uncontrolled phase II clinical trial in which untreated or previously treateds ymptomatic patients with Waldenstrom’s macroglobulnemia (n = 27) received bortezomib on a 21-day cycle until two cycles .

Treon, et al. (2007) reported on an uncontrolled clinical study which found bortezomib to be an active agent in relapsed and refractory Waldenstrom’s macroglobulinemia. The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. The investigators observed that sensory neuropathies resolved or improved in nearly all patients following cessation of therapy.

Guidelines from the National Comprehensive Cancer Network (p. WLMPL-B, 2011) indicates bortezomib with rituximab ”particularly” for primary treatment of symptomatic hyperviscosity in Waldenstrom’s macroglobulinemia. However, NCCN appears to accept the combination with Rituxan without hyperviscosity also.

Velcade is currenlty under a French study for this diagnosis: Efficacy of Bortezomib (Velcade(R)) in Patients With Advanced Waldenström Macroglobulinemia (WM2), NCT00777738. This trial is designed to evaluate the efficacy and toxicity in patients with advanced Waldenström’s Macroglobulinemia disease. A Belgian study, NCT00142129, was completed in 2007 and not yet published.

A. Vijay and M. A. Gertz
Waldenstrom macroglobulinemia
Blood, June 15, 2007; 109(12): 5096 – 5103.

Chen CI, Kouroukis CT, White D, et al; National Cancer Institute of Canada Clinical Trials Group. Bortezomib is active in patients with untreated or relapsed Waldenstrom’s macroglobulinemia: A phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(12):1570-1575.

Treon SP, Hunter ZR, Matous J, et al. Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom’s macroglobulinemia: Results of WMCTG Trial 03-248. Clin Cancer Res. 2007;13(11):3320-3325.

Allogeneic transplantation for Waldenstrom – pro

M Levin, MD — Thu, 30 Aug 2012 02:03:45 +0000

Lymphoplasmacytic lymphomas are low grade Non-Hodgkin’s lymphomas and contain small lymphocytes, plasmacytoid lymphocytes, variable numbers of transformed cells, and plasma cells. It is the nodal; equivalent of Waldenstrom’s (WM) macroglobulinemia. The question that needs to be addressed in the medical appropriateness of allogeneic transplantation and the proposed conditioning regimens for a low grade lymphoma as well as the disease specific question. In general, the literature does not confirm effectiveness of allogeneic transpalntation for indolent lymphomas. Encouraging evidence is accumulating for the efficacy of reduced intensity transplantation in indolent lymphoproliferative disorders. Allogeneic graft-versus-malignancy effects can be demonstrated and durable responses to donor lymphocytes are being reported. More follow-up is required, however, before the curative potential of allogeneic transplantation can be confirmed or generally accepted.

Only restrospective sereis are available for waldenstrom’s; they establish that Stem Cell Transplants is feasible in WM and long-term disease control can be achieved in selected patients with autologous or allogeneic SCT, even in those with refractory disease. A 2006 review, however, concluded: “Allogeneic SCT carries a much higher (40%) risk of Non Relapse Motality and should not be considered outside the context of a clinical trial.”

A . Anagnostopoulos , A . Aleman , S . Giralt Autologous and allogeneic stem cell transplantation in Waldenstrom’s macroglobulinemia: Review of the literature and future directions . Seminars in Oncology , Volume 30 , Issue 2 , Pages 286 – 290

Athanasios Anagnostopoulos, Parameswaran N Hari, Waleska S Pérez, Karen Ballen, Asad Bashey, Christopher N Bredeson, César O Freytes, Robert Peter Gale, Morie A Gertz, John Gibson, Hartmut Goldschmidt, Hillard M Lazarus, Philip L McCarthy, Donna E Reece, David H Vesole, Sergio A Giralt Autologous or Allogeneic Stem Cell Transplantation in Patients with Waldenstrom’s Macroglobulinemia.Biol Blood Marrow Transplant. 2006 Aug ;12 (8):845-54

Thomson KJ, Mackinnon S. Role of allogeneic transplantation in low-grade lymphoma and chronic lymphocytic leukemia. Curr Opin Hematol. 2006 Jul;13(4):273-9.

IVIG in Waldenstrom’s – pro

M Levin, MD — Sat, 30 Jun 2012 13:34:52 +0000

The hypogammaglobinemia and impaired T-cell function associated with Waldesntrom’s macroglobulinemia predispose patients to potentially serious infections. CLL is a similar condition to Wandenstrom’s and is much more common. IVIG is well established for CLL. UNfortunately, it is not similarly establisehd for Waldesntrom’s. IgA and IgG hypogammaglobulinemia is common in Waldenström’s macroglobulinemia and persists despite therapeutic intervention and response. A recent review found that IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström’s macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström’s macroglobulinemia patients being managed with a ‘watch and wait’ strategy.

NCCN does not mention IVIG as an adjunctive or primary treatment. More recenlty, IVIG was reported to prevent Rituxan induced flair.

Silvia Sánchez-Ramón,et al, Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy. Front Immunol. 2016; 7: 317.

Stephen M. Ansell, MD, PhD, Robert A. Kyle, MD, Craig B. Reeder, MD, Rafael Fonseca, MD, Joseph R. Mikhael, MD, William G. Morice, MD, PhD, P. Leif Bergsagel, MD, Francis K. Buadi, MD, Joseph P. Colgan, MD, David Dingli, MD, PhD, Angela Dispenzieri, MD, Philip R. Greipp, MD, Thomas M. Habermann, MD, Suzanne R. Hayman, MD, David J. Inwards, MD, Patrick B. Johnston, MD, Shaji K. Kumar, MD, Martha Q. Lacy, MD, John A. Lust, MD, PhD, Svetomir N. Markovic, MD, PhD, Ivana N. M. Micallef, MD, Grzegorz S. Nowakowski, MD, Luis F. Porrata, MD, Vivek Roy, MD, Stephen J. Russell, MD, PhD, Kristen E. Detweiler Short, RN, CNP, A. Keith Stewart, MD, Carrie A. Thompson, MD, Thomas E. Witzig, MD, Steven R. Zeldenrust, MD, PhD, Robert J. Dalton, MD, S. Vincent Rajkumar, MD, and Morie A. Gertz, MD
Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines ayo Clin Proc. 2010 September; 85(9): 824–833.

Zachary R. Hunter1 et al, IgA and IgG hypogammaglobulinemia in Waldenström’s macroglobulinemia haematol March 1, 2010 vol. 95 no. 3 470-475

Bendamustine and Ofatumumab for Waldenström’s – pro

M Levin, MD — Wed, 20 Jun 2012 15:50:24 +0000

NCCN recommends a number of regimens, amongst them bendamustine and Rituxan and ofatumumab as a single agent. However, combination of ofatumumab and bendamustine is still investigational. There are several phase 2 clinical trials in different conditions but not currently in Waldenström’s.

A. Vijay and M. A. Gertz
Waldenstrom macroglobulinemia
Blood, June 15, 2007; 109(12): 5096 – 5103.

Treon SP, Hanzis C, Tripsas C, Ioakimidis L, Patterson CJ, Manning RJ, Sheehy P. Bendamustine therapy in patients with relapsed or refractory Waldenström’s macroglobulinemia.Clin Lymphoma Myeloma Leuk. 2011 Feb;11(1):133-5.

Victorian, Brande. Managing Waldenström’s Macroglobulinemia in the Face of Limited Data and Experience
Oncology Times: 10 November 2010 – Volume 32 – Issue 21 – pp 47-49

NCCN, Waldenstrom’s MPLP-B

Read the Layperson version here.