scholarly journals Historical perspective and advances in the treatment of multiple myeloma

2011 ◽  
pp. 250-258
Author(s):  
Amir Harandi ◽  
Damian A. Laber
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Historical Perspective ◽  
Liposomal Doxorubicin ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Pegylated Liposomal Doxorubicin ◽  
New Agents ◽  
Overall Survival Rates

Corticosteroids and melphalan were used for decades to treat multiple myeloma. Combination chemotherapy has been extensively studied with similar overall survival rates to melphalan and prednisone. In the last decade, the development of new agents has progressed significantly. Thalidomide and its newer derivatives lenalidomide, bortezomib, and pegylated liposomal doxorubicin have drastically revolutionized treatment approaches. As a result, numerous clinical trials have yielded exciting treatment strategies resulting in therapeutic advances, and improved responses and overall survival of patients. This review summarizes the international uniform response criteria for multiple myeloma and gives a historical perspective on previous therapies with updates on the newest available treatments.

scholarly journals Historical perspective and advances in the treatment of multiple myeloma

2011 ◽  
Vol 2 (4) ◽  
pp. 250
Author(s):  
Amir Harandi ◽  
Damian A. Laber
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Historical Perspective ◽  
Liposomal Doxorubicin ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Pegylated Liposomal Doxorubicin ◽  
New Agents ◽  
Overall Survival Rates

Corticosteroids and melphalan were used for decades to treat multiple myeloma. Combination chemotherapy has been extensively studied with similar overall survival rates to melphalan and prednisone. In the last decade, the development of new agents has progressed significantly. Thalidomide and its newer derivatives lenalidomide, bortezomib, and pegylated liposomal doxorubicin have drastically revolutionized treatment approaches. As a result, numerous clinical trials have yielded exciting treatment strategies resulting in therapeutic advances, and improved responses and overall survival of patients. This review summarizes the international uniform response criteria for multiple myeloma and gives a historical perspective on previous therapies with updates on the newest available treatments.

Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma

2021 ◽  
Vol 1 (2) ◽  
pp. 35-42
Author(s):  
YURIKA NOGUCHI ◽  
NORIYOSHI IRIYAMA ◽  
HIROMICHI TAKAHASHI ◽  
YOSHIHITO UCHINO ◽  
MASARU NAKAGAWA ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Survival Rates ◽  
Patient Characteristics ◽  
Newly Diagnosed ◽  
Estimated Glomerular Filtration Rates ◽  
Overall Survival Rates ◽  
Maintenance Group

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

Clinical Efficacy of Pegylated Liposomal Doxorubicin, Vincristine and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5212-5212
Author(s):  
Wen Wu ◽  
Xiaodong Gao ◽  
Lan Xu ◽  
Hua Yan ◽  
Zhixiang Shen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Median Time ◽  
Liposomal Doxorubicin ◽  
Gastrointestinal Symptoms ◽  
Pegylated Liposomal Doxorubicin ◽  
High Response Rate ◽  
Newly Diagnosed

Abstract Object: To investigate the short-term and long-term efficacy and toxicity of pegylated liposomal doxorubicin, vincristine and dexamethasone (DVD) in patients with newly diagnosed multiple myeloma (MM). Methods: Twenty-five patients (13 males, 12 females, median age 55 years) with newly diagnosed multiple myeloma were treated with pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg intravenously on day 1 plus dexamethasone 40 mg intravenously or orally on days 1–4 (DVD) for median 4.5 (2–8) cycles. Treatment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Criteria for Multiple Myeloma (2006) before initiation of each course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results: After 4.5 (2–8) courses of the median cycles, clinical response was observed in 20 patients (80%), including complete response in 4 (16%), very good partial response in 3 (12%), partial response in 10 (40%), minimal response in 3 (12%) and stable disease in 2 (8%). The median time to initial response was 1.2 months and the median time to best response was 4 months. After 25 (2–50) months of median follow-up, the median progression-free survival was 20 months, while the median overall survival has not yet been reached. The overall survival rate was 72% (18/25). The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 10, constipation in 9 patients), neutropenia (7 patients), anemia (6 patients) and thrombocytopenia (4 patients). DVD was associated with more hand-foot syndrome (4 patients) and mucitis (2 patients). Conclusions: DVD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed multiple myeloma.

Relative Stability Of Plasma Cells Immunophenotype In Multiple Myeloma Over Time

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1885-1885
Author(s):  
Benoit Tessoulin ◽  
Steven Legouill ◽  
Marion Eveillard ◽  
Nelly Robillard ◽  
Soraya Wuilleme ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Survival Rates ◽  
Prospective Trial ◽  
Multiparameter Flow Cytometry ◽  
Single Centre ◽  
Over Time ◽  
Overall Survival Rates

Abstract Emerging evidence indicates that multiple myeloma (MM) can follow a number of evolutionary pathways over a patient’s disease course. Recently, genomic data have shown the coexistence in many patients of several tumour types, which could be either genetically stable, evolving linearly or be constituted of heterogeneous clonal mixtures with predominant clones shifting over time (Keats, Blood 2012;120:1067-1076). Little is known however of immunophenotypic evolution of the myeloma cells (MM cells) during MM progression. In a retrospective single-centre analysis of tumoral immunophenotypes, we examined sequential bone marrow or peripheral blood samples from 51 MM patients. Multiparameter flow cytometry was performed to assess MM phenotype using CD38 and CD138 expression as well as intracytoplasmic light chain usage restriction in most cases. The presence or absence of CD19, CD20, CD27, CD28, CD56 or CD117 on the MM cells’surface was investigated additionally. A median of 4 of the latter antigens was examined per sample. Most MM cells were homogeneous in the expression or absence of expression of the differentiation antigens investigated. Immunophenotype changes were defined as the loss or gain of at least 1 antigen. Whenever partial expression of one or several antigens was observed on MM cells, indicating MM subsets, the presence of subclones was suspected. Samples were obtained at diagnosis and relapse for 33 MM patients, and during consecutive relapses for 18. The total amount of analysed samples was 109, with a median of 2 samples per patient (range: 2-3). A modification of immunophenotype occurred in 22 patients (43%), with one antigen change (68%), two antigens changes (18%) or three antigens changes (14%). Immunophenotypic changes are summarized in table 1. For 20% of the cases or more, this involved CD28 (n=11, balanced gain or loss) or CD27 (n=7, mostly loss). CD56 expression, scarcely negative on the first assessment, was gained at relapse in three cases. Other antigens were expressed in a stable fashion over time. Eighteen (35%) of the patients had at least a subclone on the first immunophenotype, which was lost and/or modified in 14 / 18 patients at time of subsequent relapse. There was no significant impact of immunophenotypic modifications on overall survival rates Similarly, the presence of a subclone at first examination, or the immunophenotypic change of this subclone over time was not associated with differences in overall survival rates. In conclusion, this retrospective single centre study demonstrates that the immunophenotype of MM cells is mostly stable during the course of the disease. When changes occur, they do not seem to affect the clinical course of the patients. These preliminary results need confirmation on a larger and prospective trial. Disclosures: No relevant conflicts of interest to declare.

Bortezomib and Pegylated Liposomal Doxorubicin as Induction Therapy for Adult Patients with Symptomatic Multiple Myeloma: Cancer and Leukemia Group B Study 10301.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 797-797 ◽  
Author(s):  
Robert Z. Orlowski ◽  
Bercedis L. Peterson ◽  
Ben Sanford ◽  
Asher A. Chanan-Khan ◽  
Lee M. Zehngebot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Liposomal Doxorubicin ◽  
Overall Response Rate ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Response Data ◽  
Grade 3 ◽  
Group B ◽  
Leukemia Group

Abstract Introduction: The proteasome inhibitor bortezomib in combination with pegylated, liposomal doxorubicin (PLD) has significant activity against relapsed/refractory multiple myeloma (MM). It was therefore of interest to evaluate this combination in previously untreated MM patients (pts) requiring induction chemotherapy. Methods: Patients enrolled onto Cancer and Leukemia Group B study 10301 received bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 of every 21 day cycle, along with PLD at 30 mg/m2 on day 4, for a maximum of eight cycles. Primary objectives were to determine the complete response (CR) + near-CR rate, and also to define the toxicity of this regimen in the front line setting. Secondary objectives included determining the overall response rate, the ability to collect stem cells, and the time to progression and overall survival. Results: Between June, 2004, and October, 2005, a total of 63 pts were enrolled. Adverse event (AE) data were available for 55 pts, with hematologic AEs reaching grade 3 in 14 pts (25%), and grade 4 in 5 pts (9%). Notable hematologic AEs included neutropenia (grade 3 in 16%, and grade 4 in 2% of pts), thrombocytopenia (9% and 5%, respectively), lymphopenia (11% and 2%), and anemia (7% and 2%), though there was only one episode of febrile neutropenia. Non-hematologic toxicities reaching grade 3 were seen in 32 pts (58%), while 5 pts (9%) had grade 4 non-hematologic toxicities. Fatigue (grade 3 in 16%, grade 4 in 0%), sensory neuropathy (11% and 2%, respectively), hand-foot syndrome (9% and 0%), syncope (9% and 0%), motor neuropathy (7% and 0%), dehydration (7% and 0%), rash (7% and 0%), weight loss (5% and 0%), hypotension (5% and 0%), diarrhea (5% and 0%), nausea (5% and 0%), infection (5% and 0%), and dyspnea (5% and 0%) were notable AEs seen in 5% or more of pts. Preliminary response data were available for 57 pts, of whom 9 (16%) achieved a CR or near-CR, while 58% attained at least a partial response (PR). Final response data were available for 29 pts who completed their study-directed therapy, and among these the CR + near-CR rate was 28%, with an overall response rate (PR or better) of 79% in this small cohort. Progression-free and overall survival can not yet be estimated because of a paucity of events at a median of 10 months of follow-up. Stem cell collection data is available for 6 pts after induction therapy with bortezomib and PLD, in whom a median of 13.6 x 106 CD34+ cells/kilogram were mobilized (range 11.2 – 48.6 x 106). Conclusions: These preliminary data suggest that bortezomib and PLD is well-tolerated by chemotherapy-naïve multiple myeloma patients in this study. Moreover, this steroid-free regimen has promising activity, and does not seem to compromise the ability to collect stem cells for later transplantation.

Non Pegylated Liposomal Doxorubicin in Combination with Dexamethasone and Lenalidomide (RMD) Is Active in Advanced MM

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5742-5742
Author(s):  
Gabriele Buda ◽  
Enrico Orciuolo ◽  
Martina Rousseau ◽  
Sara Galimberti ◽  
Nadia Cecconi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Tumour Cell ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Free Survival ◽  
Myeloma Cells ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated

Abstract The pharmacology of liposomal doxorubicin gives rise to a compound with major advantages that could potentially improve response and decrease toxicity. The lower toxicity, especially less cardiotoxicity, is also related to the encapsulation of doxorubicin into microscopic liposomes, which preferentially penetrate and accumulate in tumour vasculature. In addition, because myeloma cells divide slowly, the increased exposure of these cells to doxorubicin has the potential of overcoming resistance and increasing tumour cell killing capacity, theoretically resulting in improved response rates. In our hospital we treated 40 patients (24M/16F, see Table I) with of a combination regimen of lenalidomide, non pegylated liposomal doxorubicin (NPLD, Myocet®) and dexamethasone (RMD). All the patients had relapsed multiple myeloma and the majority of them were heavily pretreated (23/40 were resistant to ≥ 2 previous therapies). RMD was administered for a median of six 28-day cycles. Lenalidomide (25mg d 1-21), NPLD 40 mg/m2 d4, Dex 40 mg d1-4 and 17-20. The median age of patients was 61 years and the ORR of the combination was 58%, with 10% of patients achieving a complete or very good partial remission. In particular a high ORR (52%) resulted also in very refractory patients in third line of treatment or more. The median progression-free survival was 9.4 months, while the median overall survival was 21 months (see Table II). The most common side effect was haematological toxicity with grade neutropenia (33%), thrombocytopenia (33%) and anaemia (18%). Under thrombosis prophylaxis with aspirin 100 mg per day we observed thrombembolic complications in only in one patients. Other non haematological side effects were pain (8%), diarrhoea (8%). Neither neurotoxicity nor constitutional symptoms of grade 3/4 were found. In our study, lenalidomide in combination with NPLD and dexamethason has shown encouraging activity in heavily pretreated patients with relapsed or refractory multiple myeloma. These schemes can be additional standard of care in the treatment of patients with relapsed or refractory multiple myeloma. The addition of NPLD can play a key role in overcoming anthracycline resistance and improving the quality of response without limiting toxicity. The pharmacology of NPLD gives rise to a compound with major advantages that could potentially improve response and decrease toxicity. Because increased angiogenic activity occurs in the bone marrow of patients with multiple myeloma, this non-pegylated formulation can enhance the delivery of doxorubicin to the tumour site. In addition, because myeloma cells divide slowly, the increased exposure of these cells to doxorubicin has the potential of overcoming resistance and increasing tumour cell killing capacity, theoretically resulting in improved response rates without limiting toxicity, especially in patients who have already received at least one prior therapy. Table Characteristics of MM Patients undergoing RMD therapy Characteristics Cases Age at diagnosis (median and range) 61 (30-73) Number of patients 40 (26 M, 14 F) Stage at diagnosis Durie-Salmon (II/III) 31/40 (78%) Number of previous therapies 1 17 (42,5%) 2 10 (25%) 3 8 (20%) 45 3 (7,5%) 2 (5%) Prognostic Markers b2-microglobulin (m/L.) 2.2 (1.1 – 35)a Creatinin (mg/dl.) 0.9 (0.5 – 4.4) a Albumin (g/dl)) 4.0 (2.1 – 4.9) a Hemoglobin (mg/dl) 11.3 (5.7 – 16.4) a .aMedian (Range) Figure 1 Figure 1. Figure 2 Figure 2. Table II Progression Free Survival and Overall Survival (in months) Disclosures No relevant conflicts of interest to declare.

Gastrointestinal stromal tumor – A review of clinical studies

2019 ◽  
Vol 25 (6) ◽  
pp. 1473-1485 ◽  
Author(s):  
Ardavan Khoshnood
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Gastrointestinal Stromal Tumor ◽  
Survival Rates ◽  
Stromal Tumor ◽  
Tumor Patients ◽  
Third Line ◽  
New Treatments ◽  
Common Mesenchymal Tumor ◽  
Overall Survival Rates

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. With the advent of Imatinib, the treatment of gastrointestinal stromal tumor has been revolutionized as both the progression-free and overall survival rates have increased dramatically. Unfortunately, gastrointestinal stromal tumor patients on Imatinib do eventually fail due to resistance. Even though sunitinib and regorafenib have been shown to be highly effective as second- and third-line treatments, both have limited effects. New treatments are highly warranted for this reason. In this present review, 25 registered pharmacological clinical trials at ClinicalTrials.gov have been reviewed and show promising and encouraging results.

Effect of the combination of pegylated liposomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8002-8002 ◽  
Author(s):  
J. L. Harousseau ◽  
A. Nagler ◽  
P. Sonneveld ◽  
J. Bladé ◽  
R. Hajek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Combination Therapy ◽  
Liposomal Doxorubicin ◽  
Randomized Study ◽  
Pegylated Liposomal Doxorubicin ◽  
Proteasome Inhibition ◽  
Phase Iii ◽  
Combination Group ◽  
Refractory Multiple Myeloma

8002 Background: Proteasome inhibition with bortezomib is a standard of care for patients with relapsed/refractory multiple myeloma (MM). Recently, we reported the results of an interim analysis for the DOXIL-MMY-3001 study, a large multi-national, phase III, randomized study of patients with previously treated MM demonstrating that the combination of pegylated liposomal doxorubicin (PLD) and bortezomib resulted in a 45% risk reduction of experiencing disease progression over bortezomib alone (Orlowski et al, 2006 ASH Meeting, Abstract #404). The improvement in TTP was associated with an overall survival (OS) trend favoring the combination therapy (P=0.113; hazard ratio[HR], 1.48, 95% Confidence Interval [CI], 0.91 to 2.41). We now present an updated survival analysis with a median follow up of 11 months. Methods: 646 patients at 123 centers in 18 countries received either intravenous bortezomib, 1.3 mg/m2, on days 1, 4, 8, and 11 of every 21-day cycle, or the same bortezomib regimen with PLD, 30 mg/m2, on day 4. Results: As previously reported, median TTP was improved from 6.5 months for bortezomib alone to 9.3 months for the PLD+bortezomib combination (P=0.000004; HR, 1.82; 95% CI, 1.41 to 2.35). The complete+partial response rate was 43% for bortezomib and 48% for PLD+bortezomib (P=0.251). Median duration of response was increased from 7.0 months (95% CI, 5.9 to 8.3) to 10.2 months (95% CI, 10.2 to 12.9) with combination therapy (p=0.0008). Updated OS analysis showed PLD+bortezomib significantly improved OS (p<0.05; HR, 1.41, 95% CI, 1.002 to1.97). Both groups received a median of 5 cycles of treatment. The safety profile of the combination was consistent with the known toxicities of the two agents. Grade 3/4 adverse events were more frequent in the combination group primarily due to increase in myelosuppression and GI toxicities. Conclusions: PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed/refractory MM. [Table: see text]

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