FEIST- WEILLER CANCER CENTER MULTIPLE MYELOMA GUIDELINES. Updated December, Authors: Nebu Koshy, MD. Binu Nair, MD. Gerhard Hildebrandt, MD

Transcription

1 FEIST- WEILLER CANCER CENTER MULTIPLE MYELOMA GUIDELINES Updated December, 2011 Authors: Nebu Koshy, MD Binu Nair, MD Gerhard Hildebrandt, MD Reinhold Munker, MD Glenn Mills, MD

2 Mandatory initial tests for multiple myeloma 1. Serum protein electrophoresis, immunofixation 2. Quantitative immunoglobulins 3. Routine urinalysis, 24 hour urine collection for electrophoresis and immunofixation 4. Unilateral Bone marrow aspirate and/or biopsy* 5. Bone marrow cytogenetics (metaphase karyotype and FISH)** 6. Radiologic skeletal survey, including spine, pelvis, skull, humeri and femurs; magnetic resonance imaging in certain circumstances 7. Serum β2 microglobulin and LDH 8. Measurement of serum free light chains * CD 138 used to accurately determine percentage of plasma cells in bone marrow biopsies. Clonality of plasma cells established by identification of immunoglobulin in the cytoplasm of plasma cells by immunoperoxidase staining or by immunofluorescence * Bone marrow biopsy also performed as 1) it may provide a more reliable assessment of plasma cell infiltration, and 2) may obviate the need for a repeat procedure should the bone marrow aspirate prove to be inadequate. The highest number of plasma cells obtained by either procedure is recorded for the purpose of diagnosis ** Standard metaphase cytogenetics can separate hyperdiploid from nonhyperdiploid patients and can capture uncommon additions, deletions and translocations. ** FISH preferably after sorting of plasma cells with probes that look for del 17p13, t(4,14), t(14;16), del 13, t(11;14), 1q21 amplification Follow up treatment 1. Serum protein electrophoresis preferred to assess response 2. For light chain myeloma 24 hour urine collection with total protein and urine electrophoresis to quantify Bence Jones proteinuria recommended 3. For non- secretory or oligosecretory myeloma free light chains serially assessed 4. Bone marrow examination not needed to assess response if myeloma can be monitored by serum and urine studies 5. Bone marrow aspiration and/or biopsy only indicated to establish complete response. Complete response has prognostic implications as it may predict for longer duration of response and survival

3 6. No indication to repeat metaphase karyotype, FISH studies or flow cytometric studies as routine follow up 7. No indication to repeat skeletal survey if responding to treatment unless he develops bone symptoms Tests to be performed at relapse 1. Serum β2 microglobulin and LDH 2. Bone marrow aspirate and/or biopsy if clinically indicated i.e suspicion of hyposecretory myeloma progression or when myelodysplastic syndrome is considered i.e presence of cytopenia 3. Cytogenetics (metaphase karyotype and FISH) repeated only if normal or not done at baseline If already had high risk feature on cytogenetic or FISH analyses, no need to look for it again at relapse 4. Skeletal survey to detect possible lesions at risk for fracture Other imaging studies (CT, MRI, PET- CT) to detect soft tissue masses arising from bone lesions, or extramedullary disease indicated according to clinical circumstances High risk disease - - High serum β2 microglobulin level and International Staging system stages II and III, incorporating high β2 microglobulin and low albumin are considered to predict higher risk disease Detection of any cytogenetic abnormality is considered to suggest higher- risk disease, specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by FISH of t(4;14), t(14;16) and del17p. Detection of 13q deletion by FISH only, in absence of other abnormalities is not considered a high risk feature. Transplant eligible patients 1. Induction regimen of choice Bortezomib- Lenalidomide- Dexamethasone Dosing and schedule: Bortezomib 1.3 mg/m2 iv days 1, 8 and 15 Lenalidomide 25 mg oral days 1-14 Dexamethasone 40 mg days 1,8, 15 and 22 Repeated every 3 weeks Once weekly bortezomib and dexamethasone preferred unless urgent need for rapid disease control.

4 2. Plan for stem cell collection after 4 cycles, adequate for 2 transplants 3. Autologous stem cell transplant once best response is achieved following above induction 4. Second Autologous stem cell transplant if fail to achieve a VGPR with the first SCT 5. Lenalidomide maintainenance for maximum of 2 years or until progression of disease which ever is earlier. Discuss benefits vs risks of mainatenance therapy with lenalidomide following transplant especially risk of secondary cancers with patients Transplant ineligible patients Induction regimen of choice Bortezomib- Melphalan- Prednisone Dosing and schedule: Bortezomib 1.3mg/m2 iv days 1,8,15 and 22 Melphalan 9mg/m2 oral days 1-4 Prednisone 60mg/m2 oral days 1-4 Repeated every 35 days x 9 cycles Adjunctive Treatment Bisphosphonates 1. All patients receiving primary myeloma therapy should be given bisphosphonates (pamidronate or zoledronic acid) 2. All patients should receive a comprehensive dental examination and appropriate preventive dentistry before bisphosphonate therapy. 3. It is generally recommended to continue bisphosphonate therapy for 2 years; however 1 year is sufficient for patients in CR/nCR. Bisphosphonates should be resumed if the patient experiences a relapse with new onset of skeletal- related events. 4. Monitor for renal dysfunction with use of bisphosphonates 5. Monitor for osteonecrosis of the jaw

5 Others 1. Low- dose radiation therapy (10-30Gy) can be used as palliative treatmenrt for uncontrolled pain, for impending pathologic fracture or impending cord compression 2. Limited involved fields should be used to limit the impact of irradiation on stem cell harvest or impact on potential future treatments 3. Orthopedic consultation should be sought for impending or actual long- bone fractures or bony compression of spinal cord or vertebral column instability 4. Consider vertebroplasty or kyphoplasty for symptomatic vertebral compression fractures 5. Consider erythropoietin for anemic patients 6. Intravenous immunoglobulin therapy should be considered in the setting of recurrent life- threatening infection 7. Consider pneumovax and influenza vaccine 8. PCP, herpes, and antifungal prophylaxis if high- dose dexamethasone regimen 9. Herpes zoster prophylaxis for patients treated with bortezomib 10. Prophylactic anticoagulation recommended for patients receiving thalidomide- based, or lenalidomide with dexamethasone therapy 11. The choice of thromboprophylaxis depends on risk of venous TE associated with a given regimen. Aspirin is only recommended for patients with no risk factors or one individual/myeloma related risk factor. Low- molecular weight heparin or full dose warfarin is recommended for patients with at least two individual /myeloma- related risk factors. Relapsed multiple myeloma 1. If relapse or progressive disease per International Myeloma Working Group Response Criteria more than 6 months after stopping therapy, the initial treatment regimen that successfully controlled the myeloma initially can be reinstituted when possible 2. Other options: - Bortezomib with pegylated doxorubicin in patients who have not previously received bortezomib and have received at least 1 prior therapy - Lenalidomide or thalidomide monotherapy for steroid intolerant individuals - Bendamustine - High dose cyclophosphamide

6 References: 1. Consensus recommendations for standard investigative work up: a report of the International Myeloma Workshop Consnensus Panel 3.Blood. 2011;117: Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011;117: International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood.2011;117: International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for high- dose chemothetapy wit autologous stem cell transplantation. Leukemia. 2009;13: Kumar S, Flinn IW, Hari PN, et al. Novel three- and four drug combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for newly diagnosed multiple myeloma: Encouraging resultsfrom the Multi- Center, Randomized, Phase 2 Evolution Study. ASH Annual Meet Abstr 2009;114: Richardosn PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010:116: Attal M, Cristini C, Marit G, et al. Lenalidomide maintainance after transplantation for myeloma. J Clin Oncol 2010;28 ( suppl):15 s (abstr 8018) 8. McCarthy PL, Owzar K, Anderson KC, et al. Phase III intergroup study of lenalidomide versus placebo maintainence therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB J Clin Oncol 2010;28(suppl):15s abstr San Miguel JF, Schlag R, Kuageva NK, et al. Bortezomib plus melphalanand prednisone for initial treatment of multiple myeloma. N Eng J Med 2008;359: Mateos, M.V. et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomized trial. Lancet Oncol. 11, (2010) 11. Palumbo A, Bringhen S, Rossi D et al. A prospective, randomized, phase III study of bortezomib, melphalan, prednisone and thalidomide (VMPT) versus bortezomib, melphalan

7 and prednisone (VMP) in elderly newly diagnosed myeloma patients. [abstract 652]. Blood (ASH Annual Meeting Abstracts). 2008;112: Rajkumar SV.Multiple myeloma: 2011 update on diagnosis, risk stratification, and management. Am. J. Hematol. 86:57-65, Orlowski RZ, Nagler A, Sonnevald P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with brtezomib alone in relapsed or refractory multiple myeloma: Combination therapy improves time to progression. J Clin Oncol 2007;25: Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: