Current Treatment Approaches to Newly Diagnosed Multiple Myeloma

2021 ◽  
Vol 44 (12) ◽  
pp. 690-699
Author(s):  
Susanne Ghandili ◽  
Katja C. Weisel ◽  
Carsten Bokemeyer ◽  
Lisa Beatrice Leypoldt
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Plasma Cell ◽  
Cell Clone ◽  
Unmet Need ◽  
Continuous Treatment ◽  
High Dose ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

<b><i>Background:</i></b> Multiple myeloma is a so far incurable malignant plasma cell disorder. During the past 2 decades, treatment paradigms substantially changed when novel drugs were introduced initially in treatment of relapsed disease and subsequently also in first-line treatment. <b><i>Summary:</i></b> Up to now, first-line treatment differs between patients initially classified as transplant eligible and those who are considered as nontransplant eligible. Transplant-eligible patients receive a primary proteasome inhibitor (PI)-based induction which is being combined with an immunomodulating agent and a CD38-directed monoclonal antibody followed by high-dose melphalan therapy and autologous stem cell transplantation with subsequent maintenance treatment with lenalidomide. Patients who are considered as nontransplant eligible receive upfront treatment preferentially with a continuous combination treatment either with a CD38-directed monoclonal antibody in combination with the immunomodulating agent lenalidomide or a lenalidomide-PI combination followed by lenalidomide maintenance. <b><i>Key Messages:</i></b> Primary goal of the initiated treatment is to induce a rapid and deep remission which ideally leads to an eradication of the residual plasma cell clone in sense of a minimal residual disease negativity. Achievement of long-term remission with limited toxicity despite continuous treatment strategies and maintenance or improvement of life-quality is key. Despite successful treatment options, specific difficult-to-treat subgroups, especially patients with high-risk myeloma remain with inferior prognosis and a clear unmet need for novel therapeutic strategies. Future concepts will evaluate cellular treatments and other innovative immunotherapies in first-line treatment in curative intention.

scholarly journals Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in Czech Republic

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4894-4894
Author(s):  
Tereza Popkova ◽  
Ludek Pour ◽  
Ivan Spicka ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Survival Analysis ◽  
Czech Republic ◽  
Partial Response ◽  
Complete Response ◽  
High Dose ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment

Abstract Introduction: Although highly effective agents and novel therapeutic strategies are being developed, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has not been overcome in the first-line treatment for fit patients (pts) with multiple myeloma. The objective of this work is to retrospectively analyze the use of this procedure in newly diagnosed Czech patients. Methods: Data were derived using the Czech Myeloma Group Registry of Monoclonal Gammopathies. By February 2 nd 2021, a total of 2154 newly diagnosed multiple myeloma patients who underwent HDT/ASCT were identified. Results: At the time of multiple myeloma diagnosis, the median age was 59 years; 24%/56%/14%/5%/1% pts were ECOG 0/1/2/3/4; 44%/32%/24% pts were ISS stage I/II/III; 14.5%/17.5%/68% and 84%/16% pts were Durie-Salmon stage I/II/III and subclassification A/B, respectively. The combinations of agents used in the induction regimen were proteasome inhibitor (PI), immunomodulatory drug (IMiD) and glucocorticoid (GC) in 28.5% (613/2154) pts; PI, GC and chemotherapy (CHT) in 24.8% (534/2154) pts; GC and CHT in 22,5% and IMiD, GC and CHT in 16.1% (346/2154). Other combination of drugs was used in 8.2% (177/2154) pts. It was registered that 3.7% (79/2154) induction regimens were switched to a different combination because of toxicity, patient's choice, poor peripheral venous access or other reasons. Single HDT/ASCT was performed in 77.3% (1665/2154) cases whereas tandem HDT/ASCT was given to 11.8% (254/2154) patients. In 10% (215/2154) cases, the transplantation technique was not specified. Nine percent (193/2154) patients were treated within a clinical study. The median progression free survival (mPFS) and the median overall survival (mOS) of the whole cohort was 28.9 and 92.1 months, respectively. Information about response to treatment before and after the high-dose therapy were available for 75.7% (1627/2154) and 92.2% (1987/2154) patients, respectively. Disease status at the time of HDT/ASCT was defined as stringent complete response (sCR) at 2.2% (36/1627), complete response (CR) at 11.9% (194/1627), very good partial response (VGPR) at 38.2% (621/1627), partial response (PR) at 40.9% (666/1627), minimal response (MR) at 3.6%, (58/1627), stable disease (SD) at 2.2% (36/1627), progressive disease (PD) at 1% (16/1627) patients. The overall response rate (ORR) on day 100 was 92.8% (sCR: 10.5% [209/1987], CR: 22.4% [446/1987], VGPR: 35% [696/1987], PR: 24.8% [493/1987], MR: 2.7% [54/1987], SD: 1.4% [27/1987], PD: 3.1% [62/1987]). We also performed a survival analysis of patients progressing up to 18 months after HDT/ASCT (n=1219) versus patients progressing in more than 18 months (n=935). The median OS was 41.5 versus 124.9 months, respectively. An analysis of the role of tandem HDT/ASCT in this real-world cohort will be presented at the conference. Conclusion: Globally as well as in the Czech Republic, HDT/ASCT is an important therapeutic approach in the first-line treatment of multiple myeloma. Our analysis of 2154 newly diagnosed transplant-eligible patients confirms high effectiveness - ORR of 92.8%, mPFS of 28.9 months, and long-term survival reaching mOS of 92.1 months. Disclosures Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

RAD (Lenalidomide, Adriamycin and Dexamethasone) Is a Novel and Very Effective Induction Regimen in Newly Diagnosed Multiple Myeloma Preceding a Risk-Adjusted Transplant Strategy,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3967-3967
Author(s):  
Stefan Knop ◽  
Christian Langer ◽  
Monika Engelhardt ◽  
Lars O Muegge ◽  
Christoph Röllig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Interim Analysis ◽  
Research Funding ◽  
Current Phase ◽  
Induction Treatment ◽  
High Dose ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 3967 Background Triple combinations utilizing dexamethasone, at least one of the “novel drugs” and either an alkylating agent or an anthracycline are currently considered standard induction regimens in newly diagnosed multiple myeloma (MM). In patients (pts) deemed medically fit, subsequent autologous (auto) stem cell transplantation (SCT) yet is a mainstay of care. Whether allogeneic (allo) SCT in first line treatment of MM further improves prognosis remains, however, a matter of debate. We have shown the RAD regimen to be highly effective and well tolerated in relapsed and refractory MM. Therefore, we decided to integrate this combination as a means of induction into the up-front management. Patients and methods The current phase-II trial (DSMM XII) was designed to include pts up to the age of 65 years with newly diagnosed, symptomatic MM. We chose four cycles of RAD induction (lenalidomide 25 mg/day d 1–21; infusional adriamycin 9 mg/m2 and day d1-4; dex 40 mg d1-4 and 17–20; pegfilgrastim 6 mg d 6) every 4 weeks followed by chemomobilization (cyclophosphamide, etoposide) of peripheral blood stem cells. Thromboprophylaxis by low molecular weight heparin is mandatory. All pts are scheduled to receive two transplants, the first of which being an auto SCT following standard high-dose melphalan (200 mg/m2). A subsequent allo SCT after preparation with treosulfan/fludarabin is scheduled for pts featuring at least one cytogenetic or serologic risk factor (RF). Those without any RF (“very favourable risk”) are to proceed to a second auto SCT. All patients will receive 12 months of lenalidomide maintenance. The primary end point of this trial is response to risk-adapted transplant as assessed after second SCT. This is the first planned efficacy interim analysis after 50 pts having terminated induction treatment. Results 148 pts with a median age of 55.5 (range, 30–66) years have been enrolled by 16 German centers between 9/2009 and 7/2011. In addition to the intended sample size, 2 pts had progressive disease for a total of 52 pts being evaluable for post-induction response according to the IMWG criteria. 32 pts (62%) had ISS stage II and III disease and all except three were evaluable for cytogenetic analysis based on fluorescence in situ hybridization (FISH). Incidences of chromosomal abnormalities were as follows: deletion of 13q, 31%; translocation (4;14), 15%; and deletion of 17p, 12%. Overall response rate was 79% including a 52% rate of at least very good partial response (VGPR). Seven pts (13%) achieved confirmed complete response (CR) and stringent CR. 18/52 pts (35%) experienced severe treatment-emergent adverse events (t-SAEs) with an incidence of hematologic events of 4%. Incidences of infections and venous thromboembolism were 8% and 6%, respectively. Conclusions Results from this interim analysis indicate RAD to be a very effective and well tolerated induction protocol in newly diagnosed MM. High-quality response (VGPR or better) to induction is known to be a major prognosticator for long-term prognosis in a given patient. Thus, combination of RAD with risk-adjusted SCT may contribute to enhanced disease control in a substantial proportion of pts. Disclosures: Knop: Celgene Germany GmbH: Consultancy. Off Label Use: Lenalidomide in combination with dexamethasone and adriamycine in first line treatment of multiple myeloma. Langer:Celgene Germany GmbH: Consultancy. Gramatzki:Novartis, Celgene: Consultancy, Research Funding. Einsele:Celgene Germany GmbH: Consultancy, Honoraria. Bargou:Celgene Germany GmbH: Consultancy, Honoraria, Research Funding.

scholarly journals Haematopoietic Score for the Prognostic Evaluation of Multiple Myeloma Patients Undergoing First-line Treatment With a Bortezomib-based Regimen

2020 ◽  
Author(s):  
JingSong He ◽  
XiaoYan Yue ◽  
XiaoYan Han ◽  
DongHua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Multivariable Analysis ◽  
New Drugs ◽  
Line Treatment ◽  
First Line ◽  
Prognostic Predictors ◽  
Cell Percentage ◽  
Treatment Centre ◽  
First Line Treatment

Abstract Backgroud: It is very important to evaluate the prognosis of multiple myeloma (MM) patients before starting treatment. Although haematopoietic status may have a significant impact on patient survival, it has not received sufficient attention in current clinical practice.Methods:This was a retrospective study of 150 newly diagnosed MM patients treated in one hematonosis treatment centre from May 2013 to June 2016, all of whom received first-line treatment with a bortezomib-based regimen.The effects of haematopoietic factors, including haemoglobin levels (Hgb <100 g/L), mean corpuscular volume (MCV>99.1 fL), and platelet count (<150 × 10E9/L), on the prognosis of the patients were analysed. Each of the above factors was assigned a value of 1 to generate a haematopoietic score.Results: According to the results, 59 (39.3%) patients had a score of 0, 43 (28.7%) had a score of 1, 29 (19.3%) had a score of 2, and 19 (12.7%) had a score of 3. The median PFS times were 43.1, 24.5, 32.6 and 14.2 months, respectively (P<0.001), and the median OS times were NR, 47.1 months, NR and 31.4 months, respectively (P<0.001). Multivariable analysis showed that the R-ISS stage (3 vs 1-2, HR, 1.4), haematopoietic score (3 vs 0-2, HR, 1.91) and plasma cell percentage (>30%, HR, 1.96) are independent prognostic predictors for PFS; age (≤65 years, HR, 0.54), the Durie-Salmon stage (3B vs 1-3a, HR, 2.96), haematopoietic score (3 vs 0-2, HR, 2.53) and the bone marrow plasma cell percentage (>30%, HR, 2.35) are independent prognostic predictors of OS. Conclusion: This study suggests that the haematopoietic score can be used to evaluate the prognosis of newly treated MM patients in the era of new drugs. However, there is still a need to enlarge the number of cases and carry out prospective research to validate this conclusion.

scholarly journals Hematopoietic Score for the Prognostic Evaluation of Multiple Myeloma Patients Undergoing First-Line Treatment With A Bortezomib-Based Regimen

2021 ◽  
Author(s):  
JingSong He ◽  
XiaoYan Yue ◽  
XiaoYan Han ◽  
DongHua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Multivariable Analysis ◽  
Line Treatment ◽  
First Line ◽  
Prognostic Predictors ◽  
Cell Percentage ◽  
Bone Marrow Plasma ◽  
First Line Treatment

Abstract Background: It is very important to evaluate the prognosis of multiple myeloma (MM) patients before starting treatment. Although hematopoietic status may have a significant impact on patient survival, it has not received sufficient attention in current clinical practice. Methods: This was a retrospective study of 328 newly diagnosed MM patients received first-line treatment with a bortezomib-based regimen. The effects of hematopoietic factors, including hemoglobin (Hgb) levels, mean corpuscular volume (MCV), and platelet count (Plt) on the prognosis of the patients were analysed. Results: Hgb<100 g/L, MCV>99.1fL and Plt<150×109/L significantly affect the progression-free survival (PFS) and overall survival (OS) of MM patients, each of the above factors was assigned a value of 1 to generate a hematopoietic score. According to the results, 93 (28.4%), 103 (31.4%), 90 (27.4%) and 42 (12.8%) patients had a score of 0, 1, 2, 3, respectively. The median PFS were 38.7, 55.9, 23.9 and 16.7 months, respectively (P<0.001), and the median OS were not reached (NR), 68.4months, 53.6 and 33.2 months, respectively (P<0.001). Multivariable analysis showed that hematopoietic score (2-3 vs 0-1, HR, 1.64) and bone marrow plasma cell percentage (>30%, HR, 1.54) are independent prognostic predictors for PFS; age (≥70 years, HR, 1.67), hematopoietic score (2-3 vs 0-1, HR, 1.60), serum creatinine level (>177umol/L, HR, 2.15) and bone marrow plasma cell percentage (>30%, HR, 1.81) are independent prognostic predictors of OS. Conclusions: This study suggests that the hematopoietic score can be used to evaluate the prognosis of newly treated MM patients in the era of new drugs. However, there is still a need to enlarge the number of cases and carry out prospective research to validate this conclusion.

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