Cancer Treatment Today » Lymphoma/Myeloma/Leukemia

VDT-PACE for Myeloma – pro

M Levin, MD — Mon, 10 Sep 2012 19:44:17 +0000

There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research and Therapy (MIRT): Total Therapy I (from 1989 through 1994) and Total Therapy II (from 1996 to 2004). TT II used VDT-PACE for 4 cycles. Results have shown that patients treated on these studies had better outcomes (meaning patients have lived longer and had better responses to treatment) when compared to patients treated with standard chemotherapy. The newest incarnation is Total Therapy III, an ongoing study where Velcade is be incorporated.
As of April 2005, 162 patients were enrolled and these were compared to 314 comparable TTII patients who were enrolled on the Thalomid arm. First and second transplant on TT3 were completed faster, at medians of 3 and 5 months, compared to 5 and 10 months, respectively, in the TTII group. The probability of achieving ≥ near-CR (n-CR: only immunofixation positive) at 12 months was 81% with TT3 and 64% in TT2 (p=.001). Treatment-related mortality at 12 months was 4% with TT3 and 6% with TT2 (p=.3, the incorporation of Velcade upfront therefore appears to be more effective in inducing ≥ n-CR, but was associated with an increase in toxicity, especially in patients > 65 years. It is too early to assess OS and EFS and to determine if this approach impacts the outcome of patients with high risk features. However, the 2012 ASCO Educational Book supports DT and DVT as an induction regimen. It says on p. MS-11 that thalidomide is a Category 2 recommendation and mentions DVT as an acceptable choice, albeit with anti-coagulation.

Paul G Richardson, Constantine Mitsiades, Irene Ghobrial, Kenneth Anderson. (2006) Beyond single-agent bortezomib: combination regimens in relapsed multiple myeloma. Current Opinion in Oncology 18:6, 598-608

Robert Z Orlowski & Erik L Zeger Targeting the proteasome as a therapeutic strategy against haematological malignancies Expert Opinion on Investigational Drugs February 2006, Vol. 15, No. 2, Pages 117-130

http://www.asco.org/ASCOv2/Home/Education%20%26%20Training/Educational%20Book/PDF%20Files/2012/zds00112000508.PDF, 2012

Barlogie B, Anaissie E, van Rhee F, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. British Journal of Haematology. 2007;138:176-185

Primary CNS Lymphoma – pro

M Levin, MD — Mon, 10 Sep 2012 19:41:11 +0000

Primary nervous system lymphomas (PCNSL) are aggressive malignancies, exhibiting one of the worst prognoses among lymphomas. The best treatment modality for PCNSL has not yet been identified. A recent consensus reached an agreement that intrathecal chemotherapy can be left out if a sufficiently high dose of MTX is given intravenously. Moreover, many investigators are joining forces to optimize the collection of patient information and the performance of clinical trials. This will ensure a more rapid accrual in this rare disease and the conduct of several concomitant trials for different patient subgroups based on age and other prognostic factors. Strictly speaking a high dose methotrexate regimen, is recommended by NCCN or the Consensus Meeting (Summary, stated below). While all experts agree that ideally more trials are needed, the consensus meeting was held precisely because they are not expected to be performed due to rarity of this disease. Treatments that comply with the NCCN and Consensus guidelines should be considered favorably. Long term results of sequential high-dose MTX containing chemotherapy followed by high-dose carmustine/thiotepa plus ASCT (±whole brain irradiation) is safe and leads to high survival rates after first line in eligible patients with newly diagnosed PCNSL(Kasenda et al). However, NCCN(2011, PCNS-3) recommends it only for relapsing disease: “Consider high-dose chemotherapy with stem cell rescue(level 2B recommendation). In addition to the high dose therapy with stem cell rescue, NCCN lists retreatment with high dose methotrexate, systemic chemotherapy and re-irradiation, as well as supportive care.

Gauthier J et al, Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bull Cancer. 2017 Dec;104(12S):S131-S135.

B. Kasenda et al, Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma—a long-term follow-up study Ann Oncol (2012)

NNC, PCSN Lymphoma 2019

Combined Rituxan and Campath for CLL – pro

M Levin, MD — Mon, 10 Sep 2012 19:31:55 +0000

Lay Summary: Combining two antibodies against CLL is being explored

Rituximab, an anti-CD20 monoclonal antibody, has only recently provoked interest for the treatment of CLL. It is now widely used, both as a single agent and in combination with chemotehrapy. Alemtuzumab is a recombinant, fully humanized, monoclonal antibody against the CD52 antigen. Monotherapy with alemtuzumab has produced response rates of 33% to 53%, with a median duration of response ranging from 8.7 to 15.4 months, in patients with advanced CLL who were previously treated with alkylating agents and had failed or relapsed after second-line fludarabine therapy.25–27 In addition, alemtuzumab has proven effective even in patients with poor prognostic factors, including high-risk genetic markers such as deletions of chromosome 11 or 17 and p53 mutations. It is a toxic drug and is currently used mostly in other than first line settings.

There is only one published phase II trial of the combination of the two drugs. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.

Michael Hallek, Chronic Lymphocytic Leukemia (CLL): First-Line Treatment Hematology 2005
© 2005 The American Society of Hematology

Rai KR, Freter CE, Mercier RJ, et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002;20:3891–3897.

Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554–356

William G. Wierda, Thomas J. Kipps, Michael J. Keating Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia Journal of Clinical Oncology, Vol 23, No 26 (September 10), 2005: pp. 6325-6332

Faderl S, Thomas DA, O’Brien S et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood 2003;101:3413–3415

Second transplant for myeloma -autologous and allogeneic – pro

M Levin, MD — Mon, 10 Sep 2012 19:30:15 +0000

A single or tandem autologous transplant is considered medically necessary for multiple myeloma. Autologous followed by allogeneic transplants are being explored because autologous transplants are not curative while allogeneic salvage transplants might be curative. Autologous stem cell transplantation has emerged as standard therapy for patients with multiple myeloma, primarily as a result of randomized trials performed in France over the past decade. Recent guidelines agree on several recommendations. An autologous stem cell transplant is recommended for patients with stage II or III multiple myeloma who have a good performance status. They state that evidence of benefit is strongest for patients who are younger than 55 years of age and have a serum creatinine level less than 1.7 mg/dL. They recommend using clinical judgement for patients who do not fit these criteria. Importantly, they advise early and integrated treatment with collection of stem cells before exposure to alkylating agents. They also support the use of peripheral blood stem cells over bone marrow. They suggest that early transplant produces the best results. They recommend a single transplant with high-dose Alkeran®, with or without total-body irradiation unless patients are on a clinical trial. Tandem is a prospectively planned double transplant whereas a second transplant is done only if the response to the first one is suboptimal. Tandem autologous transplants or second transplant are no longer investigational as per NCCN at this time. A second autologous stem cell transplant is sometimes performed in patients who have relapsed after an initial stem cell transplant. A second transplant is usually prospectively planned to take place within 6 months if there is not a complete response. Some myeloma centers automatically collect enough stem cells for two transplants and reserve them for a possible second transplant.

Analysis of data on 96 myeloma patients who received a second transplant following relapse, which was presented at the IXth International Workshop on Myeloma, showed that a second (salvage) transplant is a feasible option for refractory/relapsed disease. (Powles et al. Hematology J. 2003;4(suppl 1):S62. Abstract P10.3.1.) The median survival in patients receiving the salvage transplant (6.4 years) was equivalent to that typically seen with a planned tandem transplant. However, these patients represent a select subgroup of patients with relatively good prognosis. In a Czech study reported in 2004, toxicity of the first and second transplantation was similar and usually did not exceed grade II (SWOG). Transplant-related mortality was 3% (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7 have achieved prolongation of EFS II versus EFS I. In the whole group median EFS I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS) was 79.1 months; 20/32 patients were alive at the time of analysis. In a 2006 USA study, fourteen patients (median age, 52 yrs) received a second autograft for salvage, whereas 26 patients (median age, 51 yrs) underwent a reduced-intensity allogeneic transplantation (related in 18 patients and unrelated in 8 patients). The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The two groups were evenly matched with regard to other disease characteristics. After a median follow-up of 18 months for the autologous group and 30 months for the allogeneic group, the median progression-free survival (PFS) and overall survival (OS) in the 2 groups were 6.8 months versus 7.3 months and 29 months versus 13 months, respectively. Acute and chronic graft versus host disease (15%) was the most common cause of non-recurrence mortality in the allogeneic group and infections (14%) in the autologous group. Researchers from Italy have reported that an autologous stem cell transplant followed by a reduced intensity allogeneic stem cell transplant may be superior to tandem autologous transplants for newly diagnosed patients with multiple myeloma. Researchers from Spain have also reported a higher complete remission rate following auto–allo grafts versus tandem auto grafts. These two studies were presented at the 47th annual meeting of the American Society of Hematology in December 2005. The Italian study suggests benefit of a reduced intensity allogeneic stem cell transplant compared to a second autologous transplant, while the second study is equivocal with a high treatment-related mortality. A recent New England Journal of Medicine article reported superior results for an autologous, followed by allogeneic transplant. This was a prospectively planned, not a salvage transplant.

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 Trial (Abstract 41) in 2010, reported disappointing results at the American Society of Hematology Annual Meeting. The trial compared tandem autologous haematopoietic stem cell transplant with or without maintenance therapy (auto-auto) versus single autologous transplant followed by HLA matched sibling non-myeloablative allogeneic hematopoietic stem cell transplant (auto-allo) for patients with standard-risk multiple myeloma.

Results showed that the auto-allo approach at three years added no benefit to progression-free or overall survival compared with use of auto-auto. NCCN MYEL-6, 2015 recommends a second autologous transplant as Category 1 recommendation: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Conclusion:

Allogeneic transplants appeared to be a curative alternative for myeloma several years ago, but recent evidence has changed this perception and raised many questions. Autologous followed by allogeneic transplants were being explored because autologous transplants are not curative while allogeneic salvage transplants was thought to be curative. Recent studies are reversing this perception.

NCCN 2017 on p. MYEL-5 recommends additional allogeneic transplant on a clinical trial, or off trial but in relapse, not consolidation.. The International Myeloma Working Group recently published a consensus statement regarding the use of allogeneic hematopoietic stem-cell transplantation (HSCT) in myeloma. They conclude that new strategies are needed to make allogeneic HSCT safer and recommend reduced intensity conditioning in the context of clinical trials only.

Second ASCT is a feasible and safe option for salvage therapy in MM. The best outcome was observed in patients whose time to progression was >24 months after first ASCT, as these patients had a subsequent PFS lasting over 1 year and an OS of almost 6 years. NCCN recommends a second transplant, either autologous or allogeneic for progressive disease.

Gonsalves WI, Gertz MA, Lacy MQ, et al. Second auto-SCT for treatment of relapsed multiple myeloma. Bone Marrow Transplant. 2013; 48:568-573.

Ursina Gössi Barbara Jeker Behrouz Mansouri Taleghani Ulrike Bacher Urban Novak Daniel Betticher Thomas Egger Thilo Zander Thomas Pabst, Prolonged survival after second autologous transplantation and lenalidomide maintenance for salvage treatment of myeloma patients at first relapse after prior autograft. Hematologic ONCOLOGY Volume36, Issue April 2018
Pages 436-444t

NCCN myeloma 2022

Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S, Chen C, Kukreti V, Reece DE. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant. 2012 May;18(5):773-9.
NCCN MYEL-6 recommends a second transplant, either autologous or allogeneic for progressive disease.

Cook G, Liakopoulou E, Pearce R, et al. Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant. 2011;17:1638-1645.
Gonsalves WI, Gertz MA, Lacy MQ, et al. Second auto-SCT for treatment of relapsed multiple myeloma. Bone Marrow Transplant. 2013;48:568-573.
Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152.
Attal M, Lauwers-Cances V, Hulin C, et al. Autologous transplantation for multiple myeloma in the era of new drugs: a phase III study of the Intergroupe Francophone du Myeloma (IFM/DFCI 2009 Trial). Blood. 2015;731:391.

Bexxar – pro

M Levin, MD — Mon, 10 Sep 2012 19:27:26 +0000

Bexxar consists of a monoclonal antibody, tositumomab, linked to the radioactive isotope iodine iodine-131. The monoclonal antibody targets the CD20 antigen, which is found on the surface of mature B cells and B cell tumors.

The Bexxar therapeutic regimen is administered in two steps: the dosimetric and therapeutic steps. Each step consists of a sequential infusion of tositumomab followed by iodine-131 (I 131) tositumomab. The therapeutic step is administered 7 – 14 days after the dosimetric step.

The purpose of the dosimetric step is to provide a consistent radiation dose by adjusting for the individual patient’s rate of clearance of the drug. Clinical studies found that patients with high tumor burden, splenomegaly, or bone marrow involvement have a faster clearance, shorter terminal half-life, and larger volume of distribution. Patient-specific dosing, based on total body clearance, has been found to provide a consistent radiation dose, despite variable pharmacokinetics, by allowing each patient’s administered activity to be adjusted for individual patient variables.

The efficacy of the Bexxar therapeutic regimen was evaluated in a multi-center, single-arm study in forty patients with low grade or transformed low-grade or follicular large-cell lymphoma whose disease had not responded to or had progressed after rituximab therapy. Determination of clinical benefit of the Bexxar therapeutic regimen was based on evidence of durable responses. All patients in the study were required to have received prior treatment with at least four doses of rituximab without an objective response, or to have progressed following treatment.

Overall response rate was 68 percent, with a median duration of response of 16 months. One third of patients demonstrated a complete response. Among a subset of patients who were refractory to rituximab, overall response rate was 63 percent, with a median duration of response of 25 months. Twenty-nine percent of patients who were refractory to rituximab exhibited a complete response to the Bexxar therapeutic regimen.

The results of this study were supported by demonstration of durable objective responses in four single arm studies enrolling 190 patients evaluable for efficacy with Rituximab-naïve, follicular non-Hodgkin’s lymphoma with or without transformation, who had relapsed following or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47% to 64% and the median durations of response ranged from 12 to 18 months.

It is not known whether the Bexxar therapeutic regimen improves overall survival.

References:
Kaminski MS, Zelenetz AD, Press OW, et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol. 2001;19(19):3918-3128.
Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: Updated results and long-term follow-up of the University of Michigan experience. Blood. 2000;96(4):1259-1266.
Vose JM, Wahl RL, Saleh M, et al. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol. 2000;18(6):1316-1323.

PET is the same as PET/CT for restaging lymphoma – pro

M Levin, MD — Mon, 10 Sep 2012 19:24:32 +0000

PET scanning has well recognized utility in staging and restaging lymphoma. It is now covered by CMS and recommended by recent literature. In regard to PET/CT, in a recent study, the addition of PET/CT to CT changed the management decisions in approximately a quarter of NHL and a third of HD patients, mostly in early disease stages. Thus, PET/CT performed as the initial staging procedure may well obviate the need for additional diagnostic CT in the majority of patients. Based on this, I consider PET/CT to be the same as PET for the purposes of this review. NCCN recommends PET for restaging of several lymphoma subtypes, such as Peripehral T-cell and large cell lymphoma.

Cancer Care Ontario (CCO). Diagnostic imaging in lymphoma. Toronto (ON): Cancer Care Ontario (CCO); 2006 Mar 8. 17 p. [18 references]Zinzani PL, Stefoni V, Tani M, et al. Role of [18F]fluorodeoxyglucose positron emission tomography scan in the follow-up of lymphoma. J Clin Oncol 2009;27:1781–1787.
Raanani P, Shasha Y, Perry C, Metser U, Naparstek E, Apter S, Nagler A, Polliack A, Ben-Bassat I, Even-Sapir E. Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in the PET/CT era?Ann Oncol. 2006 Jan;17(1):117-22

Shankar LK, Hoffman JM, Bacharach S, et al. Guidelines for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute trials. J Nucl Med. 2006;47:1059–1066.

http://www.petscaninfo.com/zportal/portals/phys/reimbursement/clinical_indications

DLI after relapse of AML – pro

M Levin, MD — Mon, 10 Sep 2012 19:23:19 +0000

Because of the large number of acute leukemia patients who relapse after alloBMT, there has been a substantial experience in the treatment of these patients with DLI. Using median doses of >/=108 T cells/kg, DLI alone induces complete remissions in 8% of patients with ALL and 22% of patients with acute myeloid leukemia (AML). When patients who receive chemotherapy prior to DLI are included, complete response rates are significantly higher, ranging from 33% to 37%. However, follow- up of ALL patients reveals few, if any, long-term survivors, although 1 has been reported. Relapse occurs in approximately one quarter to one half of patients with AML in remission after DLI, leaving a long-term survival rate of approximately 10% to 15%.

DLI has been researched as a treatment for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia, but also acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin’s disease, and non-Hodgkin’s lymphoma. Studies are limited due to small numbers but they have provided evidence that DLI can establish a graft-versus-leukemia/lymphoma effect.

Fewer patients with relapsed myelodysplasia have been treated with DLI. However, because myelodysplasia progresses more slowly than AML, the rate of complete remissions may be higher. The natural history of myelodysplasia patients who enter into a remission following DLI has not been described.

It is not clear whether administration of induction chemotherapy at the time of relapse improves long-term survival following DLI. It is usually thought that it does but without a strong conifrmation in the literature. A randomized trial with analysis performed on an intent-to-treat basis is needed to answer this question.

Litzow, Mark R Progress and strategies for patients with relapsed and refractory acute myeloid leukemia. Current Opinion in Hematology. 14(2):130-137, March 2007.

Luznik L, Fuchs EJ. Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation.Cancer Control. 2002 Mar-Apr;9(2):123-37.

Ishikawa J, Maeda T, Kashiwagi H, et al. Successful second allogeneic peripheral blood stem cell transplantation and donor leukocyte infusion in patients with relapsed acute leukemia using the same donor as for the initial allogeneic bone marrow transplantation. Bone Marrow Transplantation. 2003; 31:1057-1059.

Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol. 2002; 20(2):405-412.

Angioimmunoblastic lymphoma- stem cell transplant – pro

M Levin, MD — Mon, 10 Sep 2012 19:11:15 +0000

Angioimmunoblastic T-cell lymphoma (AILD) is considered a variety of T-cell lymphoma, which usually occurs in adults. Symptoms include generalized lymphadenopathy (enlarged lymph nodes) and increased antibody proteins in the blood (hypergammaglobinemia). Other symptoms are fever, skin rash and weight loss. It is classified under periphreal T-cell lymphomas.

Characterized by clonal T-cell receptor gene rearrangement, this entity is managed like diffuse large cell lymphoma. Myeloablative chemotherapy and radiation therapy with autologous peripheral stem cell support has been described in anecdotal reports or as a part of populations of T-cell lymphoma patients treated with transplantation. NCCN lists both autologous and allogeneic(p. T-CELL 5) as an option. The British Standards for Hematology 2008 guideline says: “Consolidation with auto-HSCT should be considered for chemosensitive disease in first remission or after relapse LEVEL IV GRADE C”.

http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf

Tetsuo Yamazaki, Umihiko Sawada, Yoshimasa Kura, Takeyoshi Ito, Jin Takeuchi, Yoshihiro Hatta, Shingo Aikawa, Kazuhiro Takei, Hikaru Ishizuka, Minoru Saiki, Kumi Uenogawa
Lymphoma with a Dose-Intensified CHOP Regimen Followed by High-Dose Chemotherapy
A Single Institution Study Acta Haematologica 2006;116:90-95

Alizadeh AA1, Advani RH. Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies. Clin Adv Hematol Oncol. 2008 Dec;6(12):899-909

Reimer P, Schertlin T, Rüdiger T, et al.: Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J 5 (4): 304-11, 2004.

Biphosphonates for early myeloma – pro

M Levin, MD — Mon, 10 Sep 2012 19:09:02 +0000

There is increasing evidence that early treatment of smoldering myeloma with biphosphonates may e beneficial; however, the level of proof has nto yet reached the quality sufficient to change the guidelines or to modify existing coverage policies.

The recently published American Society of Clinical Oncology clinical practice guidelines for the use of bisphosphonates (BPs) in multiple myeloma do not recommend use of these drugs in patients with monoclonal gammopathies not requiring specific treatments, such as smoldering/indolent myeloma or monoclonal gammopathies of undetermined significance. The guidelines were updated in 2007 and continue to recommend that bisphosphonates not be given to myeloma patients with solitary plasmacytoma, smoldering or indolent disease, and monoclonal gammopathy of undetermined significance. The 2006 Mayo Clinic Consensus reached the same conclusion.

The most recent guideline is a European one from 2012. The panel recommends the use of biphoopshanates(BP)s in Multiple Myeloma patients suffering from lytic bone disease or severe osteoporosis. Intravenous administration may be preferable; however, oral administration can be considered for patients unable to make hospital visits. The panel agrees that BPs should be given for 2 years, but this may be extended if there is evidence of active myeloma bone disease. A recent article in 2013 New England of Medicine ( Mateos et al) suggested that high risk smoldering myeloma should be aggressively treated. This is remains controversial.

Smith A, Wisloff F, Samson D, UK Myeloma Forum, Nordic Myeloma Study Group, British Committee for Standards in Haematology. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2006 Feb;132(4):410-51. [292 references]

NCCN.ORG, Myeloma, 2012

Lacy MQ, Dispenzieri A, Gertz MA, et al. Mayo Clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc. 2006;81:1047-1053.

Terpos E, Sezer O, Croucher PI, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol 2009; 20:1303.
María-Victoria Mateos, M.D., Ph.D., Miguel-Teodoro Hernández, M.D., Pilar Giraldo, M.D., Javier de la Rubia, M.D., Felipe de Arriba, M.D., Ph.D., Lucía López Corral, M.D., Ph.D., Laura Rosiñol, M.D., Ph.D., Bruno Paiva, Ph.D., Luis Palomera, M.D., Ph.D., Joan Bargay, M.D., Albert Oriol, M.D., Felipe Prosper, M.D., Ph.D., Javier López, M.D., Ph.D., Eduardo Olavarría, M.D., Ph.D., Nuria Quintana, M.D., José-Luis García, M.D., Joan Bladé, M.D., Ph.D., Juan-José Lahuerta, M.D., Ph.D., and Jesús-F. San Miguel, M.D., Ph.D.
N Engl J Med 2013; 369:438-447August 1, 2013

Revlimid for amyloidosis – pro

M Levin, MD — Mon, 10 Sep 2012 19:06:58 +0000

Treatment for systemic amyloidosis targets the aberrant plasma cell clone to prevent further synthesis and deposition of the amyloid protein. Conventional therapy usually combines oral melphalan with prednisone (MP), shown to yield higher response rates and longer survival than colchicine or prior therapies.

A recent Phase II trial in 23 patients whose primary objective was hematologic response rate of single-agent lenalidomide in patients with primary systemic amyloidosis was reported this year. Secondary objectives were the hematologic response rate of the lenalidomide-dexamethasone combination as well as toxicity and rate of organ response for single-agent lenalidomide or the 2-drug combination. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. Another Phase II trial is referenced below.

NCCN 2011 guideline lists lenalidomide and dexamethasone.

Guidelines on the diagnosis and management of AL amyloidosis.
British Journal of Haematology 125 (6), 681-70, 2004

Hans P. Sviggum, BA; Mark D. P. Davis, MD; S. Vincent Rajkumar, MD; Angela Dispenzieri, MD Dermatologic Adverse Effects of Lenalidomide Therapy for Amyloidosis and Multiple Myeloma Arch Dermatol. 2006;142:1298-1302

Dispenzieri et al.The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis Blood 2007;109:465-470.

G. Merlini Refining therapy for AL amyloidosis
Blood, December 1, 2006; 108(12): 3632 – 3633

Vaishali Sanchorawala et al,Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial Blood, 15 January 2007, Vol. 109, No. 2, pp. 492-496.