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Waldenström Macroglobulinemia
Abstracts clinical trials for patients with pPCL. We recommend to treat these patients in the setting of a clinical trial, so that they can be treated with next generation novel agents which will hopefully contribute to improved survival of pPCL patients. During the presentation, an overview will be given of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients.
PS-068 AL Amyloidosis G. Merlini Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
Immunoglobulin light chain amyloidosis (AL) is characterized by a usually small, indolent plasma cell clone synthesizing a light chain (LC) with unique structural features causing systemic proteotoxicity and vital organ failure. The biology of the clone is being elucidated and available data indicate that it may represent an early stage of monoclonal gammopathy, possibly more susceptible to chemotherapy. Longer duration of response after high dose chemotherapy compared to MM may reflect less minimal residual disease. This is being investigated using next generation flow cytometry and mass spectrometry. The keys to effective treatment are early diagnosis and risk-adapted therapy. Early diagnosis may be facilitated by systematic use of sensitive biomarkers of cardiac and renal involvement in patients with MGUS and abnormal FLC ratio, who are at increased risk of developing amyloidosis. Advanced cardiac involvement and systemic disease reduce treatment options and efficacy. Cardiac biomarkers direct the choice of therapy. Close monitoring of clonal and cardiac response guides regimen changes and therapy duration, aiming at attaining VGPR. New data on kinetics of organ response following hematologic response indicate that achieving at least VGPR at 2 months is linked to recovery of cardiac and renal function, particularly in younger patients. Two-thirds of patients can benefit from treatment with improved quality of life and extended survival. Risk-adapted stem cell transplant can be followed by consolidation with novel agents in patients not achieving VGPR. In patients ineligible for stem cell transplantation melphalandexamethasone (MDex) is effective and well tolerated. Combinations of proteasome inhibitors with dexamethasone and alkylators show promising results and the outcome of an international phase III trial comparing MDex vs BortMDex will be presented. Treatment of relapsed/refractory AL should depend on prior therapies (seeking different mechanisms of action) and clinical presentation (neuropathy, renal failure). Doxycycline, has potential cardioprotective effect, and should be prophylactic antibiotic of choice. Trials are ongoing to test its efficacy, together with chemotherapy, in patients with advanced cardiac involvement. Three antibodies targeting amyloid deposits are being tested in clinical trials and may change the face of treatment of AL amyloidosis. This unprecedented interest in AL amyloidosis is resulting in improved patients’ outcome.
PS-069 Waldenström Macroglobulinemia S.P. Treon Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
Waldenström’s macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal IgM secreting lymphoplasmacytic cells. MYD88 and CXCR4 WHIM-like somatic mutations are present in >90%, and 30-35% of WM patients, respectively, and impact disease presentation, treatment outcome, and/or overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease related hemoglobin <10g/L, platelets <100x109/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity, and pre-rituximab for those with high serum IgM levels to pre-empt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone, or combined with alkylators (bendamustine, cyclophosphamide), proteasome-inhibitors (bortezomib, carfilzomib), nucleoside-analogues (fludarabine, cladribine) and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor modified T-cell therapy.
Debate
PS-070 Biomarker to change Therapy MRD/Imaging vs FISH/Age - in Favor of MRD/Imaging C.O. Landgren Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
Fluorescent in situ hybridization (FISH) was developed in the early 1980s to detect and localize the presence or absence of specific DNA sequences on chromosomes. Based on FISH technology, two types of multiple myeloma subtypes have been described: hyperdiploid and nonhyperdiploid subtypes. Hyperdiploid multiple myeloma is characterized by trisomies of certain odd numbered chromosomes (3, 5, 7, 9, 11, 15, 19, and 21) whereas non-hyperdiploid multiple myeloma is characterized by translocations of the immunoglobulin heavy chain gene (on chromosome 14, locus q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11). Although FISH is widely used, there is no randomized phase 3 trial data to support intensifying the treatment for high-risk FISH multiple myeloma or reducing the treatment for low-risk FISH multiple myeloma. Using modern molecular profiling assays, recent translational investigations have generated insights that significantly challenge the
15th International Myeloma Workshop, September 23-26, 2015
- e35
PS-068 AL Amyloidosis G. Merlini Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
Immunoglobulin light chain amyloidosis (AL) is characterized by a usually small, indolent plasma cell clone synthesizing a light chain (LC) with unique structural features causing systemic proteotoxicity and vital organ failure. The biology of the clone is being elucidated and available data indicate that it may represent an early stage of monoclonal gammopathy, possibly more susceptible to chemotherapy. Longer duration of response after high dose chemotherapy compared to MM may reflect less minimal residual disease. This is being investigated using next generation flow cytometry and mass spectrometry. The keys to effective treatment are early diagnosis and risk-adapted therapy. Early diagnosis may be facilitated by systematic use of sensitive biomarkers of cardiac and renal involvement in patients with MGUS and abnormal FLC ratio, who are at increased risk of developing amyloidosis. Advanced cardiac involvement and systemic disease reduce treatment options and efficacy. Cardiac biomarkers direct the choice of therapy. Close monitoring of clonal and cardiac response guides regimen changes and therapy duration, aiming at attaining VGPR. New data on kinetics of organ response following hematologic response indicate that achieving at least VGPR at 2 months is linked to recovery of cardiac and renal function, particularly in younger patients. Two-thirds of patients can benefit from treatment with improved quality of life and extended survival. Risk-adapted stem cell transplant can be followed by consolidation with novel agents in patients not achieving VGPR. In patients ineligible for stem cell transplantation melphalandexamethasone (MDex) is effective and well tolerated. Combinations of proteasome inhibitors with dexamethasone and alkylators show promising results and the outcome of an international phase III trial comparing MDex vs BortMDex will be presented. Treatment of relapsed/refractory AL should depend on prior therapies (seeking different mechanisms of action) and clinical presentation (neuropathy, renal failure). Doxycycline, has potential cardioprotective effect, and should be prophylactic antibiotic of choice. Trials are ongoing to test its efficacy, together with chemotherapy, in patients with advanced cardiac involvement. Three antibodies targeting amyloid deposits are being tested in clinical trials and may change the face of treatment of AL amyloidosis. This unprecedented interest in AL amyloidosis is resulting in improved patients’ outcome.
PS-069 Waldenström Macroglobulinemia S.P. Treon Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
Waldenström’s macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal IgM secreting lymphoplasmacytic cells. MYD88 and CXCR4 WHIM-like somatic mutations are present in >90%, and 30-35% of WM patients, respectively, and impact disease presentation, treatment outcome, and/or overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease related hemoglobin <10g/L, platelets <100x109/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity, and pre-rituximab for those with high serum IgM levels to pre-empt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone, or combined with alkylators (bendamustine, cyclophosphamide), proteasome-inhibitors (bortezomib, carfilzomib), nucleoside-analogues (fludarabine, cladribine) and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor modified T-cell therapy.
Debate
PS-070 Biomarker to change Therapy MRD/Imaging vs FISH/Age - in Favor of MRD/Imaging C.O. Landgren Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
Fluorescent in situ hybridization (FISH) was developed in the early 1980s to detect and localize the presence or absence of specific DNA sequences on chromosomes. Based on FISH technology, two types of multiple myeloma subtypes have been described: hyperdiploid and nonhyperdiploid subtypes. Hyperdiploid multiple myeloma is characterized by trisomies of certain odd numbered chromosomes (3, 5, 7, 9, 11, 15, 19, and 21) whereas non-hyperdiploid multiple myeloma is characterized by translocations of the immunoglobulin heavy chain gene (on chromosome 14, locus q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11). Although FISH is widely used, there is no randomized phase 3 trial data to support intensifying the treatment for high-risk FISH multiple myeloma or reducing the treatment for low-risk FISH multiple myeloma. Using modern molecular profiling assays, recent translational investigations have generated insights that significantly challenge the
15th International Myeloma Workshop, September 23-26, 2015
- e35