scholarly journals Multiple myeloma: Looking beyond standards

2016 ◽  
Vol 02 (01) ◽  
pp. 023-028
Author(s):  
Esha Kaul ◽  
Sanjeev Sharma
Keyword(s):  
Multiple Myeloma ◽  
Diagnostic Criteria ◽  
Plasma Cells ◽  
Residual Disease ◽  
Early Stage ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Frequent Relapses

AbstractMultiple myeloma has been regarded as an incurable disease with frequent relapses. The diagnostic criteria have been revised multiple times to include early stage of the disease where treatment can be effective and can prolong the survival. Newer diagnostic criteria for myeloma have incorporated ≥60% plasma cells in the bone marrow and serum free light chain ratio (involved to uninvolved free light chains) of ≥100. The role of positron emission tomography-computed tomography scans has been recognized, and it has been increasingly utilized upfront in the management of multiple myeloma. Role of minimal residual disease monitoring has been studied in multiple trials and will in near future guide the treatment. Autologous stem cell transplant is still the preferred consolidation therapy after initial three or four drug induction. With the use of novel drugs combinations and with emerging treatment options the standard of care of myeloma patients will change.

scholarly journals Newly Diagnosed Multiple Myeloma: How Many Drugs Are Enough?

2021 ◽  
Vol 19 (11.5) ◽  
pp. 1347-1350
Author(s):  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell Transplant ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Future Research ◽  
Cell Transplant ◽  
Disease Response ◽  
The Past ◽  
Drug Induction

The treatment of multiple myeloma (MM) has evolved over the past decade, yet it remains a chronic disease. Several trials of 4-drug induction regimens have resulted in deepening of disease response. With the emergence of multidrug regimens, questions have arisen regarding the role of autologous stem cell transplant (ASCT) in MM therapy and available treatment options after ASCT. Clinicians have also continued to improve the efficacy of maintenance therapies. In transplant-ineligible patients, the phases of treatment are less distinct; however, several regimens have demonstrated efficacy in this clinical setting. Future research should focus on individualizing treatment approaches.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1170-1170
Author(s):  
Rebecca L. Olin ◽  
David L. Porter ◽  
Selina M. Luger ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Response To Therapy ◽  
Cell Transplant ◽  
Significant Difference

Abstract Introduction: Autologous stem cell transplant (ASCT) as part of initial therapy has been shown to prolong survival of patients with multiple myeloma, with some achieving durable complete remission. However, the majority of patients ultimately relapse after ASCT and require salvage treatment. Options for the treatment of such patients have increased significantly over recent years, including not only novel chemotherapeutic and biological agents but also additional ASCTs. We performed a retrospective analysis of our experience with salvage ASCT for multiple myeloma to determine which clinical variables influence outcome. Methods: Between October 1992 and February 2005, we performed 342 ASCTs for multiple myeloma. Twenty-six of these were salvage transplants for relapsed disease after prior ASCT, and all were included in the analysis. Patients who received two planned (tandem) ASCTs were not included. Results: The median age at diagnosis was 47 (range 25–66), and median ISS and DS stages at diagnosis were 1 and 2, respectively. The initial ASCT was melphalan-based in 21/26; six (23%) achieved a complete response (CR) to the initial transplant, and fifteen (58%) achieved a partial response (PR). The median event-free survival (EFS) after the initial transplant was 19.5 months (range 2–60). The median time between initial and salvage ASCT was 2.6 years (range 0.3–7.6). Twenty-two patients (85%) received non-transplant therapy between ASCTs, and the median number of lines of therapy prior to salvage ASCT was 3. At the time of salvage ASCT, the median age was 52.5 (range 28–69). Fourteen patients received melphalan alone, eight received melphalan/TBI, and four received other regimens. Eleven patients (42%) achieved a response to therapy (1 CR, 10 PR). One patient (4%) died of transplant-related toxicity. The median follow-up after salvage ASCT is 12 months (range 0.2–58). Median EFS is 9 months, and median overall survival (OS) is 36 months. The 2-year EFS is 14%, and 2-year OS is 52%. On univariate analysis, both response to and EFS after initial transplant significantly predict improved EFS after salvage transplant (p=0.0008 and p=0.0065 respectively). Both also predict improved OS (p=0.03 and 0.0005 respectively). A greater than 12 month interval between first and second transplant also correlated with OS (p=0.04). There was no significant difference in EFS or OS by preparative regimen. Interestingly, type of response to the salvage transplant (CR/PR or less than PR) did not predict improved EFS or OS. Conclusion: This study suggests that salvage ASCT after relapse from initial ASCT is a feasible therapy for patients with heavily treated multiple myeloma, particularly those with a prolonged response to the first transplant.

Chromosome 1p21 Deletion Defines a Subgroup of Multiple Myeloma with Poor Clinical Outcomes Independent of del (13q), del(p53), t(4;14) or 1q21 Amplification.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2475-2475
Author(s):  
Hong Chang ◽  
Connie Qi ◽  
Allan Jiang ◽  
Wei Xu ◽  
Trieu Young ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Factor ◽  
Genetic Risk ◽  
Plasma Cells ◽  
Prognostic Significance ◽  
Suppressor Gene ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Median Percentage ◽  
Chromosome 1Q

Abstract Amplifications involving chromosome 1q and deletions involving 1p are frequent events in multiple myeloma (MM). The pathogenesis and clinical significance of these anomalies is largely unknown but CKS1B amplification at 1q21 detected in 30–40% of MM patients is associated with disease progression. As karyotyping and SNP based mapping analysis identify a minimal common deletion region involving the 1p21 locus, we used FISH combined with cytoplasmic light chain detection (cIg-FISH) to investigate the prevalence and prognostic significance of del(1p21) in a cohort of 186 MM patients undergoing autologous stem cell transplant. CIg-FISH detected hemizygous 1p21 deletions in 18% of the cases. The median percentage of clonal plasma cells harboring del(1p21) was 55% (range 20–95%). The presence of 1p21 deletions was strongly correlated with CKS1B amplification (p=0.004), t(4;14) (p= 0.027), and del(p53) (p=0.04), but not with del(13q) or t(11;14). There was no association between del (1p21) and other biological factors including age, gender, Hb, albumin, C-reactive protein, beta-2 microglobulin level, isotype or bone marrow plasmacytosis. Patients with 1p21 deletions had significantly shorter progression-free (median 10.5 vs. 25.4 months, p=0.0001) and overall survivals (median 33.9 months vs. not reached, p=0.001) than those without such deletions. On multivariate analysis, del(1p21) was an independent risk factor for progression free (p< 0.0001) and overall survivals (p=0.0005) after adjusting for other genetic risk factors including del(13q), del(p53), t(4;14) and CKS1B amplification. Our results indicate that del(1p21) is a novel genetic risk factor and warrant inclusion of this genetic aberration in the risk-stratification of MM. Further studies are required to identify candidate tumor suppressor gene(s) at the 1p21 locus and explore their role in the molecular pathogenesis of MM.

Outcomes and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

Role of PET/CT As a Measure of Minimal Residual Disease (MRD) Negativity Among Patients with Myeloma Post Autologous Stem Cell Transplant (ASCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4202-4202
Author(s):  
Ajay K. Nooka ◽  
Jonathan L. Kaufman ◽  
A. Tuba Karagulle Kendi ◽  
Yan Li ◽  
Chikaodili O Obidike ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Residual Disease ◽  
Standardized Uptake Value ◽  
Response Assessment ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Pet Ct ◽  
Lytic Lesions

Abstract Background: In the context of improved novel therapeutic anti-myeloma regimens using combinations of antibodies and other small molecules, measuring the efficacy of therapy is an ongoing challenge. Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC), polymerase chain reaction (ASO-PCR), next-generation sequencing are sensitive tests that are becoming more significant as improved therapies result in deeper responses, however challenges remain, such as standardizing these testing methods. 18F Fluorodeoxglucose Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that can provide essential information in diagnosis and management of MM. PET/CT has high sensitivity (80-90%) and specificity (80-100%) to detect MM lesions. PET/CT also has a recently acknowledged role in prognostic information. Standardized uptake value maximum (SUVmax) is a widely used PET/CT parameter for assessment of therapy response in a variety of cancers. Recent publication by Zamagni et al showed that in addition to the presence of three or more focal lesions, a maximum standardized uptake value (SUVmax) of over 4.2 and presence of extramedullary disease were negative prognostic factors. Our aim in this study was to evaluate the prognostic role of PET/CT in MM patients post ASCT at day 100 restaging. Methods: We have identified 130 myeloma patients that underwent autologous stem cell transplant (ASCT) from 09/2014 until 04/2015. Along with their hematologic restaging post-ASCT for response assessment per International Myeloma Working Group (IMWG) criteria, patients also underwent PET/CT for MRD assessment. After excluding 3 patients that underwent tandem transplants, and one patient that received stem cell boost, 102 patients were evaluable for the current analysis (24 patients did not undergo PET/CTs). We have done an exploratory analysis with previously described SUVmax cut off of <2.0 (Waheed S) and <4.2 (Zamagni E). Results: The median age of the patients that underwent ASCT was 64 years (range: 38-76 years). 77 pts (75%) received melphalan 200 mg/m2, 22 pts (22%) received melphalan 140 mg/m2, 2 pts received melphalan+bortezomib and 1 pt received BEAM regimen as conditioning regimen. Median time from day 0 to response assessment is 98 days (range: 55-189 days). Hematological restaging shows that 89% of patients achieved ≥VGPR (SCR: 46% and CR: 11%). 13 pts did not have prior lytic lesions while 89% had lytic lesions (one lesion: 4%, two lesions: 2% and multiple (≥3): 82%). PET/CT negativity was achieved among 63% of the patients. At SUV cut off of <2.0 and <4.2, PET/CT negativity was achieved among 64% of the patients and 83% of the patients respectively. Taking the patients that have achieved SCR, for the same cut offs, PET/CT negativity rates were 59% and 76% respectively (Table 1). Conclusions: Negative PET/CT rates post-ASCT are in accordance with previously published studies. With taking SUVmax as sole criteria for assessing MRD negativity, false positive PET/CT results will continue to remain a challenge. Although SUVmax is the most widely used PET/CT parameter, it has limitations. There are other PET/CT parameters mean or peak standardized uptake values (SUVmean, SUVpeak); metabolic tumor volume (MTV); total lesion glycolysis (TLG); standardized added metabolic activity (SAM); and, normalized standardized added metabolic activity (NSAM) used in clinical practice and research. These PET/CT parameters may have role as prognostic imaging probes in MM patients post ASCT. With longer follow up to assess PFS and OS, we can evaluate the prognostic impact of using PET/CT as MRD measure. Table 1. PET parameters and hematological responses Response Response rates PET positive PET negative PET positive (≥SUV 2.0) PET negative (<SUV 2.0) PET positive (≥SUV 4.2) PET negative (<SUV 4.2) SCR 46 19 27 19 27 11 35 CR 11 7 4 6 5 3 8 VGPR 34 9 25 9 25 3 31 PR 10 2 8 2 8 0 10 PD 1 1 0 1 0 1 0 ≥CR 57 26 31 25 32 14 43 ≥VGPR 91 35 56 34 57 17 74 Disclosures Nooka: Onyx Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Gleason:Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Lonial:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

scholarly journals Phase II Study of the Combination of Interleukin-2 with Zoledronic Acid As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5697-5697 ◽  
Author(s):  
Gabriele Buda ◽  
Rita Fazzi ◽  
Giovanni Carulli ◽  
Sara Galimberti ◽  
Paola Sammuri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Zoledronic Acid ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Gamma Delta

Abstract Background: Multiple myeloma is still today an incurable disease. The many therapeutic techniques and new therapies proposed in recent years have extended survival but did not allow for healing. Further study allowed to demonstrate that a maintenance could be useful to control the progression of disease. However, there is no clear indication for which maintenance has to be used after a first line of induction therapy. The technique of allograft, used in patients at highest risk, demonstrates that the immune response to the residual disease plays a key role in the success of this technique. Among the major players in response to myeloma, in allogeneic stem cell transplantation, gamma delta lymphocytes play a significant action: complete response after allogeneic few months later (also the molecular level) happen in parallel with the presence in the bone marrow of a significant proportion of lymphocytes with gamma delta oligoclonal expression of TCR rearrangements. Zoledronic acid induces proliferation of these cells by the production of several cytokines, in particular interleukin-2 (IL-2). Furthermore, T lymphocytes Vdelta2 are proved to be crucial antineoplastic mediators and, after expansion in vitro, capable of controlling tumor growth in animal models. These data confirm the hypothesis that gammadelta lymphocytes have a role in controlling the growth of myeloma plasma cells and can be active on the residual disease after autologous stem cell transplant. We planned to evaluate the role of the association of Zoledronate and IL-2 in vivo as post ASCT maintenance therapy in patients with newly diagnosed multiple myeloma (NDMM). Methods: This is a single arm phase II multicenter ongoing study of the combination of IL-2 with zoledronic acid as maintenance therapy for NDMM patients post ASCT. The primary objective was to establish safety and efficacy of IL-2 as maintenance therapy. The secondary objective was to evaluate the immunological expansion of gamma delta lymphocytes. Eligible patients had undergone ASCT, with melphalan as a preparative regimen. At July 2016, forty two patients in very good partial remission (VGPR) have been enrolled in the study (total planned enrollment: 43 pts) and started maintenance therapy 90-180 days post ASCT. Maintenance schedule included IL2 and zoledronic acid. IL2 was administered at a fixed dose of 2 x 106UI from day 1 to day 7 for the first cycle and with the maximum tolerated dose (up to a max of 8 x 106UI) from day 1 to day 7 for subsequent cycles (dose escalation of 25% in each cycle in the absence of toxicity). Zoledronic acid was infused 4 mg iv on day 2. This dosing regimen is repeated every 28 days until disease progression. Adverse events were graded by NCI-CTCAE v4. Response was assessed by the modified International Uniform Response Criteria. Results and toxicity: 42 patients (pts) have been enrolled with a median age of 59 (range 42-72); 50% were male and 50% female. All the 42 pts have received a median of 11 cycles (range 1-23). Of the 42 pts 21 remain on therapy (data at July 2016), 21 pts are off study: 9 due to progressive disease (PD) and 12 due to consent withdrawal. Among the 9 pts with PD, the median PFS post ASCT was 12 months (2-18 months). Of the 42 pts, 33 (79%) not progressed after a median of 13 months (range 1-33) and the median PFS has not been reached. 7/42 patients (17%) reached complete remission. Peripheral and bone marrow analysis of gamma delta lymphocytes expansion to evaluate the level of immune response is still under examination. Grade 1/2 hematologic adverse events (AEs) included: grade 1 (G1) anemia (3 pts), G1 neutropenia (3). Grade 1/2 drug-related non-hematologic AEs included: G1 fever (25) G2 fever (8); G2 constitutional symptoms (joint pains) (20); G2 constipation (4); G1/2 nausea (10); G1 fatigue (15), G1/2 cutaneous rash (2). Conclusions: Long term administration of combination of IL-2/zoledronate as maintenance therapy post ASCT is feasible. The incidence of non hematologic adverse events (in particular fever) were manageable with no dose escalation of IL-2 over 5 x 106UI. This immunological approach, without any chemotherapeutic drug, seems to be able to control the disease and to obtain the complete remission in a subgroup of myeloma patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Multiple Myeloma

Hematology ◽  
2001 ◽  
Vol 2001 (1) ◽  
pp. 157-177 ◽  
Author(s):  
William S. Dalton ◽  
P. Leif Bergsagel ◽  
W. Michael Kuehl ◽  
Kenneth C. Anderson ◽  
J. L. Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
Cell Transplant ◽  
Disease Evolution ◽  
Activating Mutations ◽  
Conditioning Regimens ◽  
Preclinical And Clinical Studies ◽  
The Impact

Abstract Multiple myeloma (MM) is a malignancy of the plasma cell characterized by migration and localization to the bone marrow where cells then disseminate and facilitate the formation of bone lesions. Unfortunately, while treatment of this disease is effective in palliating the disease, and even prolonging survival, this disease is generally regarded as incurable. Understanding the basic biology of myeloma cells will ultimately lead to more effective treatments by developing target based therapy. In Section I, Dr. Bergsagel discusses the molecular pathogenesis of MM and shares insights regarding specific chromosomal translocations and their role in the genesis and progression of MM. New information regarding FGFR3 as an oncogene as well as how activating mutations may contribute to disease evolution and may be an important target for novel therapeutics of MM is presented. In Section II, Dr. Anderson elaborates on novel therapeutic approaches to MM also targeting fundamental genetic abnormalities in MM cells. Both preclinical and clinical studies of novel agents including PS-341 and IMiDs are highlighted. In Section III, Dr. Harousseau discusses the role of autologous stem cell transplant in MM. He highlights clinical trials addressing the question of conditioning regimens and the impact of tandem transplants. He also addresses the role of allogeneic BMT and the use of attenuated dose conditioning regimens (so called mini-allogeneic transplants) in the treatment of MM. In Section IV, Dr. Dalton provides an overview of the current state of myeloma therapy and summarizes the different and exciting approaches being undertaken to cure this disease.

Sign in / Sign up

Export Citation Format

Share Document