New Vision of Myeloma The treatment model and outcome of patients with newly diagnosed multiple myeloma that are not suitable for transplantation in the real world

A retrospective analysis published in Annals of Hematology in July 2021 evaluated the clinical and demographic characteristics of patients with newly diagnosed multiple myeloma (MM) and conventional treatment in the real world, from Spain, who are not suitable for transplantation, The treatment mode and outcome, the editor will take you to learn more about the research results
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Research background MM is the second most common hematological malignant tumor.
It is estimated that the global 5-year prevalence rate is close to 230,000 cases
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MM occurs at any age, and it is extremely rare to be diagnosed before the age of 30, and only one-third of newly diagnosed patients are younger than 65 years old
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The median age at diagnosis of MM patients in Europe and the United States is approximately 69 years, that is, nearly half of newly diagnosed patients in high-income countries are ≥70 years old
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In addition to chemotherapy toxicity and disease progression, elderly patients with MM are usually frail, with multiple comorbidities, including renal failure, which may lead to premature death
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In the past ten years, the emergence of new drugs such as proteasome inhibitors and immunomodulators has significantly improved the 5-year and 10-year survival rates of ordinary MM patients, but the improvement in elderly patients is small, and the survival time is similar to that reported in previous decades, and shorter than younger patients.

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In addition to the low proportion of autologous stem cell transplantation, other factors may lead to a poor prognosis for elderly patients with MM
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Clinical guidelines provide limited recommendations for the management of elderly and complex MM patients
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In the real world, due to various limitations (definition of elderly patients, etc.
) and the inability of clinical trials to answer the treatment questions of complex patients, clinicians have limited tools to formulate appropriate treatment plans for each patient, leading to heterogeneous prospects for MM treatment sex
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This retrospective analysis assesses the profile, treatment pattern, and outcome of newly diagnosed MM patients undergoing routine treatment in Spain
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Research methods: A retrospective, non-interventional, multi-center, observational study that included patients from 20 Spanish hospitals who initiated first-line treatment between 2012 and 2016 and were not suitable for transplantation of newly diagnosed MM patients.
The randomized controlled trial (RCT) was excluded.
) In the patient
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The clinical and demographic characteristics of patients were collected, including gender, age, ECOG PS, glomerular filtration rate (GFR), and serum lactate dehydrogenase (LDH) levels
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According to the International Staging System (ISS) for staging, bone marrow fluorescence in situ hybridization (FISH) detects the risk of cytogenetic abnormalities, and high-risk patients are defined as t (4; 14), t (14; 16) and deletion (17p) ( p53)
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Treatment options include: (1) Bortezomib-based VMP (bortezomib+melphalan+prednisone in the VISTA trial); (2) Bortezomib-based VMP lite (Mateos et al.
study); ( 3) Non-VMP based on bortezomib: including bortezomib + cyclophosphamide + dexamethasone (VCD), bortezomib + thalidomide + dexamethasone (VTD), bortezomib + dexamethasone ( VD), bortezomib + adriamycin + dexamethasone (PAD), bortezomib + cyclophosphamide, bortezomib monotherapy; (4) melphalan-based regimen: melphalan + prednisone (MP); (5) Based on lenalidomide program: including lenalidomide + low-dose dexamethasone (Rd), lenalidomide + bortezomib + dexamethasone (RVd) and so on
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Treatment outcomes are described by overall survival (OS), progression-free survival (PFS), and overall response rate (ORR, defined as partial response or better)
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Study results Study the characteristics of patients During 2012-2016, a total of 688 newly diagnosed MM patients received treatment
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Among them, 22 patients lacked treatment plan data, 4 patients participated in RCT during the survey period, and finally 675 patients were enrolled, with a median age of 75.
6 (6.
7) years old.
The main demographic and clinical characteristics are shown in Table 1
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348 cases (52.
6%) were elderly patients (>75 years old), 441 cases (65.
3%) had cytogenetic risk stratification data, and 114 cases (25.
9%) were high-risk patients
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Table 1 The treatment characteristics are based on the fact that the bortezomib regimen is the most prescribed treatment regimen in the first-line (Table 2)
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The median (IQR) duration of treatment for each treatment plan is as follows: BORT VMP 9.
43 months (3.
55, 11.
96), BORT VMPa 9.
74 months (5.
75, 11.
20), BORT n-VMP 3.
78 months (1.
69, 6.
19), The lenalidomide-based regimen is 12.
45 months (1.
51, 29.
63), the melphalan-based regimen is 7.
39 months (3.
12, 11.
07) and the other regimens are 2.
84 months (0.
95, 14.
19)
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According to the clinical and demographic characteristics of patients, the probability of using each program has different trends (Figure 1)
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Less frail patients (such as ECOG PS 0/1) and low-risk patients (such as ISS stage I, normal or mildly impaired GFR, and standard-risk cytogenetic abnormalities) are more likely to receive VMP-based regimens, while high-risk patients ( For example, patients with ECOG PS ≥ 2, ISS stage III, severely impaired GFR, high LDH levels, and high-risk cytogenetic abnormalities) are more often treated with bortezomib-based non-VMP regimens
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Patients over 80 years old have a lower probability of using VMP-based schemes (especially VISTA schemes)
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In addition to the bortezomib-based VMP regimen, 25% of patients over the age of 80 receive melphalan+prednisone regimen and other first-line recommended treatment regimens
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The median (range) ages used in each regimen are as follows: Bort VMP 74 years (62-87), BORT VMP 76 years (57-88), Bort n-VMP 75 years (41-88), based on lenalidomide Plan 76 years old (62-86), based on Melphalan plan 82 years old (67-91) and other plans 82 years old (60-90)
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Among the 669 patients with data, 293 (43.
8%) patients required dose adjustment, the most common bortezomib VMP regimen based on weakening (eg, lite) [n = 116/185 (63.
7%)], followed by Lenalidomide regimen [(n = 11/24(45.
8%)], based on melphalan regimen [n = 27/66(41.
5%)], based on bortezomib VMP regimen [(n = 65/158(41.
1) %)]
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Table 2 Figure 1 Treatment Outcomes The median PFS of MM patients in this study was 15.
3 months (95% CI 14.
0-16.
9) (Figure 2a), which was affected by baseline ECOG PS, high serum LDH levels, and high-risk cytogenetics Abnormalities and the significant impact of first-line treatment regimens
.
Of the
518 evaluable patients, 405 (78.
2%) patients achieved partial remission or better, 161 (31.
1%) achieved very good partial remission, and 86 (16.
6%) achieved complete remission.
Remission
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The overall remission rates for patients ≤ 75, 76-80, and> 80 years old were 80.
8%, 82.
9%, and 66.
4%, respectively
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The median OS of MM patients in this study was 33.
5 months (95% CI 29.
1-37.
2) (Figure 2b), which was significantly affected by ECOG PS, ISS staging, GFR, LDH levels, cytogenetic risk, first-line treatment, and age ( Figure 3)
.

Depending on the regimen, the median OS ranged from 10.
5 months (95% CI 2.
8-40.
3) with the “other” regimen to 52.
2 months (95% CI 41.
8-62.
0) with the bortezomib-based regimen
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Figure 2 Figure 3 Research conclusions The results of this retrospective analysis of real-world MM patients in Spain show that there is a high degree of heterogeneity in first-line treatment, especially in elderly and high-risk patients, who usually receive poorer combination therapy
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These results indicate that clinicians have limited objective criteria for making treatment decisions for elderly patients and patients who are not suitable for transplantation of MM, and that treatment options for elderly patients should be selected based on specific pre-treatment assessments of risks and benefits
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References: 1.
Cejalvo MJ, Bustamante G, González E, et al.
Treatment patterns and outcomes in real-world transplant-ineligible patients newly diagnosed with multiple myeloma.
Annals of Hematology.
2021 Jul;100(7):1769-1778 .
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