How should we treat newly diagnosed multiple myeloma patients?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 488-495 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús F. San Miguel

AbstractMultiple myeloma (MM) is the second most frequent hematological disease. Two-thirds of newly diagnosed MM patients are more than 65 years of age. Elsewhere in this issue, McCarthy et al discuss the treatment of transplantation candidates; this chapter focuses on the data available concerning therapy for non-transplantation-eligible MM patients. Treatment goals for these non-transplantation-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life. Until recently, treatment options were limited to alkylators, but new up-front treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) plus alkylating agents have significantly improved outcomes. Other nonalkylator induction regimens are also available and provide a novel backbone that may be combined with novel second- and third-generation drugs. Phase 3 data indicate that maintenance therapy or prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. The potential for novel treatment regimens to improve the adverse prognosis associated with high-risk cytogenetic profiles also requires further research. In summary, although we have probably doubled the survival of elderly patients, this group requires close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy while maintaining their quality of life.

2015 ◽  
Vol 11 (1) ◽  
pp. 50
Author(s):  
María-Victoria Mateos ◽  

Multiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring quality of life. Melphalan plus prednisone has been the classic backbone to which proteasome inhibitors and immunomodulatory drugs were added and, recently, lenalidomide plus low-dose dexamethasone emerged as a new standard of care, free of alkylator, and also as a backbone to which second-generation proteasome inhibitors are being added. Monoclonal antibodies will take part of these treatments regimens in the future. Prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. Finally, elderly patients under treatment require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining their quality of life.


2015 ◽  
Vol 11 (01) ◽  
pp. 43
Author(s):  
María-Victoria Mateos ◽  

Multiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring quality of life. Melphalan plus prednisone has been the classic backbone to which proteasome inhibitors and immunomodulatory drugs were added and, recently, lenalidomide plus low-dose dexamethasone emerged as a new standard of care, free of alkylator, and also as a backbone to which secondgeneration proteasome inhibitors are being added. Monoclonal antibodies will take part of these treatments regimens in the future. Prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. Finally, elderly patients under treatment require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining their quality of life.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2972-2972 ◽  
Author(s):  
S. Verelst ◽  
F. Termorshuizen ◽  
C. Uyl-de Groot ◽  
M. R Schaafsma ◽  
R. Ammerlaan ◽  
...  

Abstract Abstract 2972 Thalidomide (T) with melphalan/prednisone (MPT) was defined as a standard treatment in elderly patients with multiple myeloma (MM) based on 5 randomized trials. Treatment with MPT not only showed improved response rate, significantly better time to response as well as quality of response but also a significant improvement of event free survival (EFS), progression free survival (PFS) and overall survival (OS). In one of these trials, HOVON 49, a prospective Health related – Quality of life (HRQoL) was initiated in order to asses the impact of T on QoL. (Wijermans et al, J Clin Oncol 28:3160-6). Patients aged >65 years with newly diagnosed symptomatic MM were randomized to receive 8 cycles of MP or MPT, followed by T maintenance in MPT arm. 284 patients were included in this HRQoL side study (MP: n=149, MPT: n=135). HRQoL was assessed with the EORTC core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at pre-determined intervals during treatment. Treatment-related toxicity WHO grade 2–4 occurred in 60% of MP and 87% of MP-T treated patients. Most frequently found were neutropenia-related infections, neurotoxicity (mostly T induced peripheral neuropathy) and myelotoxicity. The QLQ-C30 subscales Physical Function (p=0.044) and Constipation (p<.001) showed a treatment related improvement during induction in favour of the MP arm. During T maintenance, the scores for the QLQ-MY24- Paraesthesia became significantly higher in the MPT arm (p<.001). The QLQ-C30 subscales Pain (p=0.12), Insomnia (p=0.068), Appetite loss (p=0.074) and the QLQ-MY24- item Sick (p=0.086) scored marginally better during T maintenance. The overall QoL scale QLQ-C30-HR-QOL showed a significant time trend towards more favourable mean values during protocol treatment but did not reveal differences between MP and MPT. For the QLQ-C30 subscales Emotional function and Future perspectives, difference in favour of the MPT arm from the start of treatment was observed (p=0.018and p=0.045 respectively) with no significant ‘time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. Since the first questionnaire was filled out prior to treatment but after randomization we hypothesise that the awareness of being treated with a medication that holds out a prospect of better treatment outcome may in itself be associated with improved feeling of well-being and hope for the future. This prospective study shows that the higher frequency of adverse effects associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective. Disclosures: No relevant conflicts of interest to declare.


Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 498-507 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús F. San Miguel

AbstractMultiple myeloma is the second most frequent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want definitively to cure the disease. Treatment goals for transplant-eligible and non–transplant-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life. For young patients, HDT-ASCT is a standard of care for treatment, and its efficacy has been enhanced and challenged by the new drugs. For elderly patients, treatment options were once limited to alkylators, but new upfront treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) combined or not with alkylators have significantly improved outcomes. Extended treatment of young and elderly patients improves the quality and duration of clinical responses; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. This review summarizes progress in the treatment of patients with newly diagnosed multiple myeloma, addressing critical questions such as the optimal induction, early vs late ASCT, consolidation and/or maintenance for young patients, and how we can choose the best treatment option for non–transplant-eligible patients.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3461-3461 ◽  
Author(s):  
Hendrik Brockhoff ◽  
Christian Meyer zum Büschenfelde ◽  
Murwan Ayoub ◽  
Hartmut Goldschmidt ◽  
Hans-Juergen Salwender

Abstract Background: During the last 15 years there has been a substantial improvement in treatment options for patients with multiple myeloma. For patients younger than 65 years high dose chemotherapy with melphalan and autologous stem cell transplantation is still regarded as the standard therapy. This very effective treatment regimen is now widely used for more than 20 years. However, the therapy of elderly patients (> 70 years) with HDT-ASCT has only been a reserved option for a selected group of patients with a lower biological age. Therefore, for these patients only few studies have analyzed the role of HDT-ASCT regarding overall survival (OS), progression free survival (PFS) and risk assessment-which is our study subject. In addition we want to compare HDT-ASCT with the current standard of treatment for older patients like the continuous lenalidomide and dexamethasone regime (Rd) or bortezomib based regimes. Method: We retrospectively analyzed 62 elderly patients with a median age at ASCT of 71.3 years with multiple myeloma who underwent HDT-ASCT treatment at the Asklepios Hospital Altona in Hamburg, Germany between 2004 and 2013 (3 previously treated with HDT-ASCT and 59 previously untreated). Overall these patients received 86 ASCT. Primary scopes of interest were OS, PFS and treatment related mortality (TRM). Secondary outcome variables were melphalan-dosage, chronic renal failure (Durie Salmon stage A/B), tandem-therapy, ISS-Score, as well as best response after therapy. OS was calculated from beginning of therapy until death of any cause. PFS was calculated from beginning of therapy until progression. Results: The median OS was 60.8 months. TRM was 0%. Median PFS was 33.3 months (n=40). The following factors were significant regarding OS: 1. Chronic renal failure (39 vs. 65.6 months; p=0.03). 2. Higher ISS-Score (ISS III: 33.7 vs. ISS I/II: 76.7 months; p= 0.013). The following factors showed a non statistically significant trend regarding OS: 1. High melphalan dosage, at least once 200mg/m² melphalan, during HDCT-ASCT (70.3 vs. 53 months; p=0.1). 2. Response after therapy (complete remission (CR) / very good partial remission (VGPR): 74.6 vs. partial remission / minimal remission / stable disease: 59.4 months; p= 0.088). 3. Tandem therapy (single transplantation: 60.6 vs. tandem transplantation: 96.3 months; p= 0.127). Conclusion: With a median OS of more than 5 years and a TRM of 0% high dose chemotherapy with melphalan is a valid treatment option for selected elderly patients with multiple myeloma aged > 70 years. The median OS and PFS (60.8 months; 33.3 months) in our patient group was higher than published data with lenalidomide or bortezomib based treatments (e.g. Rd), which has a median OS of 58.9 months and a of PFS 26 month (Facon et al. 2015, Clinical Lymphoma Myeloma and Leukemia, Vol: 15, p: e134). At relapse fewer patients are eligible for HDT-ASCT than de novo patients, therefore HDT-ASCT should be used as first line therapy for suitable patients. Adverse effects of long time glucocorticoid, bortezomib and lenalidomide treatment also have a negative impact on the quality of life for myeloma patients and can lead to irreversible medical consequences. Of note, the treatment duration with high dose melphalan is shorter and has a lower cost than other treatment options for multiple myeloma, which can lead to long treatment free intervals and therefore improve the quality of life for patients. Disclosures: No relevant conflicts of interest to declare. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5493-5493
Author(s):  
Yuan Yao ◽  
Dehui Zou ◽  
Aijun Liao ◽  
Xiaoxia Chu ◽  
Wei Wang ◽  
...  

Background: Multiple Myeloma (MM) is a disease of the elderly, whose prognoses are highly heterogeneous. Hence International Myeloma Working Group (IMWG) proposed geriatric assessment (GA) in 2015, including daily activity and comorbidity status, to better discriminate between fit and frail patients (Palumbo et al, 2015). However, IMWG recruited patients from clinical trials instead of real world practices. Therefore we studied GA in elderly MM patients consecutively in China, along with other perspectives which are known to be problematic in elderly population that were previously left unnoticed, such as nutrition status, risk of cognitive impairment, risk of depression, and quality of life. Aim: Our study centers on the feasibility to perform a more comprehensive geriatric assessment (cGA) in elderly MM patients, current cGA status in elderly MM patients in China, and the cGA difference between Chinese patients and patients in the IMWG study. Method: From August 2017 to April 2019, we continuously recruited 336 newly diagnosed elderly (age ≥ 65) MM patients from 21 centers in China. cGA was performed at diagnosis, after treatment cycle 1, after cycle 4, and 1 year after treatment. cGA includes physical conditions (ECOG), activities of daily living (ADL), instrumental ADL (IADL), mini-nutritional assessment (MNA-SF), geriatric depression scale (GDS), mini-mental state examination (MMSE), quality of life (SF-36) and Charlson comorbidity index (CCI). Staging was assessed at baseline (International Staging System (ISS) & Revised ISS) and hematological responses were evaluated along with each cGA timepoint. Results: We pool-analyzed data of 336 newly-diagnosed elderly MM patients. The median age was 70 (range 65-88) and 25.5% of patients were older than 75 years. 336 (100%) patients were able to complete cGA, and median assessment time was 40 minutes (range 20-70). Upon diagnosis, only 34% and 37.5% of patients had full ADL and IADL respectively. 38.5% of patients had moderate to high risk of depression (GDS ≥ 6). 13.2% of patients were malnourished (MNA-SF ≤ 7), while 46.3% of patients were at risk of malnutrition (8 ≤ MNA-SF ≤ 11). 41% of patients had at least one comorbidity (CCI ≥ 1). 45.7% of patients had moderate to intermediate risk of cognitive impairment (MMSE ≤ 26). Grouping by IMWG-GA index, our study identified 59.9% patients in frail group (vs 39% in IMWG study), 15.8% in intermediate (vs 31% in IMWG) and 24.3% in fit (vs 30% in IMWG). 69% of patients received proteasome inhibitor-containing regimens and 20.7% of patients received lenalidomide-containing regimens. Best hematological responses in fit and intermediate groups were better than responses in frail group (≥ PR rate: 88.5% in fit, 94.4% in intermediate vs 77.5% in frail). Median follow up time was 10 months. To date, 215 (64%) patients have finished the cGA after cycle 1; 164 (48.8%) patients have finished the cGA after cycle 4; 91 (27.1%) patients has finished all 4 planned cGA and improvements in cGA were observed in the majority of these patients. Conclusion: Our study showed significant CGA heterogeneity in elderly MM patients. Even in the IMWG-GA "fit" group, nutrition, depression and cognitive impairment remain problems. Frail patients took up a larger proportion in Chinese elderly MM patients compared to IMWG study. Our study strongly justifies the necessity for cGA in elderly patients with MM, more so in the real world MM patients than in the clinical trials. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5574-5574
Author(s):  
Abdul Aziz Siddiqui ◽  
Kazi Najamus-saqib Khan ◽  
Arafat Ali Farooqui ◽  
Muhammad Saad Farooqi ◽  
Muhammad Junaid Tariq ◽  
...  

Introduction: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) tend to have comorbidities and/or advanced age that make this subset of patients difficult to manage with current drug regimens. Methods: A comprehensive literature search of PubMed, Embase, Clinicaltrials.gov and Web of Science was performed from inception and completed on 07/17/2019. Studies focusing on efficacy and tolerability of 3-drug regimens in patients with NDMM were included for the review. Results: Out of 3579 studies, a total of 10 (08 phase II and 03 phase III) clinical trials in last ten years (2010-2019) using 3-drug regimens in NDMM elderly pts (893M/807F) ineligible for ASCT (determined by investigators) were selected. A total of 1703/1740 NDMM pts were evaluated. Proteasome inhibitors (PIs) such as carfilzomib (C), bortezomib (V) and ixazomib (I) showed promising results in elderly transplant-ineligible NDMM pts. CLARION trial (phase III, n=955) compared two PIs (C and V) with melphalan (M) and prednisone. There was no statistically significant difference in progression-free survival (PFS) between two groups (median: 22.3 vs 22.1 months; HR: 0.91; 95% CI, 0.75-1.10, p = 0.159) as well as overall survival (OS) (HR: 1.08; 95% CI: 0.82-1.43). Difference in the least square means of the HR-QoL (Health related- quality of life) was 4.99 (p<.0001) favoring C-group. M may not be an ideal drug to combine with carfilzomib in this setting given more AEs.(Facon et al 2019). V as 3-drug regimen in combination with lenalidomide (L) in 242 pts achieved statistically significant prolonged PFS (median 43 mo) and OS (median 75 mo) with great efficacy and acceptable risk-benefit profile. (Durie et al 2017; phase III). Multinational phase II trial (n=70) by Dimopoulos et al (2019) evaluated I, with different fixed doses of cyclophosphamide (Cy). Median duration was 19 cycles, indicating the long-term tolerability of regimen. With favorable toxicity profile and maintained QoL scores, trial concluded that this therapy is tolerable in elderly transplant-ineligible NDMM pts. Tuchman et al (2017) in phase II trial (n=14) investigated (V-Cy-d) and achieved ORR of 64%, with ≥VGPR of 57%. Low dose V showed great efficacy with M yielding ORR of 86% and VGPR or better of 49% in phase II trial (n=101) that also evaluated Cy as 3-drug combination but results were more productive with M with longer PFS and OS which reduced when impact of frailty was examined on outcomes. Since toxicity was higher with M, trial suggested that 2-drug combination should be preferred in elderly frail patients. (Larocca et al 2015). Efficacy was quite promising when Bringhen et al (2014) trialed C with Cy-d; 87% OS and 76% PFS at 1 y in phase II trial (n=58) with much favorable safety profile. Monoclonal antibodies (mAb) such as elotuzumab (E) and pembrolizumab (Pe) are also tested in elderly. First study conducted on NDMM pts using humanized mAb; E, in phase II trial (n=40) by Takezako et al (2017) attained primary endpoint of the study (ORR) of (88%) and VGPR or better of 45% in Japanese pts with tolerable toxicities in elderly. No subjects on this study experienced severe peripheral neuropathy. KEYNOTE-185; a phase III multinational trial by Usmani et al (2019) evaluated Pe with Ld in 151 pts. FDA halted this study due to unfavorable benefit-risk profile; 19 deaths, 6 due to disease progression (PD), and 13 due to treatment-related AEs. Median PFS and median OS were not reached in either group. Immunomodulators such as L achieved one of the longest PFS reported in a trial of transplant ineligible patients (35 mo) by using LVd regimen in phase II multicenter trial (n=50). (O'Donnell et al 2018) Alkylating agents like bendamustine (ben) and M have been tested in different novel regimens. Decreasing intensity and increasing duration of ben resulted in better outcomes in phase II trial (n=59) by Berdeja et al (2016) and can be given as first line treatment. Ben yielded great results with low dose dexa as compared to high dose achieving 92% ORR. Original regimen was effective but relatively more toxic. Incidence of herpes and neuropathy decreased dramatically with the treatment modifications. Conclusion: Three-drug regimens having PIs, mABs, immunomodulators and alkylating agents have shown desirable results in NDMM transplant (ASCT)-ineligible elderly patients and are likely the emerging standard of care for NDMM. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.


2020 ◽  
pp. JCO.20.01370
Author(s):  
Aurore Perrot ◽  
Thierry Facon ◽  
Torben Plesner ◽  
Saad Z. Usmani ◽  
Shaji Kumar ◽  
...  

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.


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