Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China

ABSTRACT

Objectives

The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice.

Methods

This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months.

Results

CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively.

Conclusions

The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

KEYWORDS:

• Multiple myeloma
• extreme survivals
• chemotherapy
• prognostic biomarker

Introduction

Multiple myeloma (MM) is a hematological malignancy of plasma cells, which is featured by abnormal clonal proliferation of plasma cells in the bone marrow. The clinical manifestations of MM include hypercalcemia, renal impairment, anemia, and bone destruction [1]. As estimated, 16500 new MM cases and about 10300 disease-related deaths occurred in China in 2016 [2]. The prognosis of MM patients has witnessed significant advancements, primarily due to the introduction of novel therapeutic agents, such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies, along with the extensive utilization of autologous stem cell transplantation (ASCT) over the past decades [3–5]. However, the majority of MM patients would relapse and become drug-resistant, eventually become untreatable and die [6,7].

MM is a disease of notable heterogeneity, manifesting in both clinical and pathological aspects of the disease [8,9]. The heterogeneity is further amplified in the survival outcomes of MM patients. The survival of MM patients varies even when uniformly treated in random clinical trials [10–13]. Survival disparities are more distinct in real-world practice. A real-world study of data from the Swedish Myeloma Registry found that 19% of MM patients died within 1 year from diagnosis, and 5-year overall survival (OS) in MM patients was 38.3% [14]. A single center in Greece reported that 9% of MM patients had progression-free survival (PFS) longer than 7 years. There were also a bunch of exceptional responders to ASCT who had a median PFS of 13.8 years without maintenance therapy [15]. At the same time, a subset of MM patients, which account for 15–20%, have a predicted OS of less than 3 years [16]. Some patients may have more dismal outcomes with early death in 2 years [17]. These data further illustrate the substantial variability in survival outcomes among MM patients in the real-world setting.

What factors contribute to the notable disparities observed in the survival rates of MM patients, particularly when taking into account the presence of comprehensive clinical guidelines that serve as a valuable reference for making treatment decisions. Numerous unanswered questions persist within the realm of real-world clinical practice, necessitating further elucidation. In this study, we sought to comprehensively review information of MM patients derived from a prominent National Medical Center in China. Subsequently, we categorized the patients into two distinct groups characterized by extreme survival outcomes. Our investigation primarily focused on delineating the characteristics of these two MM patient cohorts, with a particular emphasis on highlighting unexpected findings that diverged from prevailing expectations.

Patients and methods

Patients

This retrospective study reviewed demographic, clinical and laboratory data of patients with MM seen in Zhongshan Hospital, Fudan University, from July 1995 to December 2021. The definition of MM using the International Myeloma Working Group (IMWG) criteria [18]. Among these 1409 MM patients, 391 were excluded due to the comorbidity of amyloidosis (AL) or pre-treated. There were 77 patients excluded for follow-up time less than 30 days. Eventually, the data of 941 newly diagnosed multiple myeloma (NDMM) patients met the eligibility criteria for inclusion in this study (Figure 1). The study was approved by the Institutional Review Board of the Zhongshan Hospital, Fudan University.

Figure 1. Flowchart of the study.

Variables

Baseline characteristics of MM patients before the initiation of treatment were collected, including sex, age, M-protein subtype, creatinine (Cr), lactate dehydrogenase (LDH), albumin (ALB), β2-microglobulin (β2-MG), Hemoglobin (Hb), calcium (Ca), Bone lesion, Extramedullary disease (EMD), Eastern Cooperative Oncology Group Performance Status (ECOG PS), and International Staging System (ISS). Cytogenetic abnormalities were determined by fluorescent in situ hybridization (FISH) of the bone marrow of the presence of t(4;14), t(14;16), t(11;14), del(13q), del(17p) and 1q gain/amplification. MM patients with t(4;14), and/or t(14;16), and/or del(17) were considered at high risk. The delineations for double-hit and triple-hit myeloma adhered to the criteria established by the Mayo Clinic's mSMART3 classification system. The response to therapy and progression was determined based on the criteria defined by the IMWG [19]. Frontline therapy was classified by the main drug and into four categories: (1) PI only, (2) IMiDs only, (3) PI/IMiDs combination, and (4) Other. The stringent complete response (sCR) category was integrated into the complete response (CR) part. PFS and OS were used to describe the survival outcomes of MM patients. PFS was measured from the time of diagnosis until disease progression or death from any cause. OS was defined from the date of diagnosis to the date of death or last follow-up. We identified a subset of MM patients into two categories, MM patients in the rapid progression (RP) group have PFS ≤ 6 months, the other is the long-term remission (LR) group incorporating MM patients with PFS ≥ 60 months.

Statistical analysis

The statistical analyses were performed using SPSS 25.0 (IBM Inc., San Francisco, CA, USA). We compared variables between two groups using appropriate statistical tests (chi-square test or Fisher’s exact test for categorical variables; t-test or the Mann–Whitney U-test for continuous variables). Survival plots of PFS and OS were estimated by the Kaplan–Meier method and compared by log-rank tests. All P-values were two-sided and less than 0.05 were considered to be statistically significant.

Results

The baseline characteristics of MM patients

A total of 941 NDMM patients were included in the analysis. The median follow-up time was 35.0 months (range, 1.0–170.5 months). 341 progression events and 261 deaths were recorded. The median PFS and OS were 33.9, 70.7 months respectively (Figure S1). The clinical data and biological characteristics of 941 NDMM patients are shown in Table 1. The median age was 64 years (range, 31–89) and 63.1% of patients were male. The M-protein subtypes found were mostly IgG in 486 (51.6%), IgA in 248 (26.4%) and light chain in 128 (13.6%). Of all the patients, 170 (18.2%) patients had renal insufficiency, 15.5% with increased LDH levels, 501 patients (53.4%) had anemia, and 79 patients (8.5%) had hypercalcemia. Among all patients, 83.9% presented with bone lesions and 8.1% had an ECOG PS of >2. A total of 42.6% of patients presented with ISS stage III, 137 patients in the Revised International Staging System (R-ISS) stage III. Among all patients, 489 (52%) received a PI-based regimen and 276 (29.3%) took PI/IMiDs combination therapy as the frontline treatment. The use of ASCT was in 133 patients (14.1%).

Table 1. Baseline characteristics of 941 NDMM patients.

Variable	n(%)
Median age, years(range)	64(31–89)
≤65	533(56.6)
66–80	361(38.4)
>80	47(5)
Male	594(63.1)
M-protein type
IgG	486(51.6)
IgA	248(26.4)
Light chain	128(13.6)
Other	79(8.4)
Cr > 2 mg/dl	170(18.2)
LDH increased(250)	143(15.5)
ALB ≥ 3.5 g/dl	523(55.8)
β2-MG ≥ 5.5 mg/L	392(42.5)
Hb < 100 g/L	501(53.4)
Ca > 11 mg/dl	79(8.5)
EMD	240(30)
Bone lesion	781(83.9)
ECOG PS > 2	76(8.1)
t(4;14)	107(18.8)
t(14;16)	15(2.6)
del(17p)	67(10.5)
ISS stage
I	245(26.6)
II	284(30.8)
III	392(42.6)
R-ISS stage
I	129(22.1)
II	318(54.5)
III	137(23.5)
Double-hit	104
Triple-hit	14
Frontline therapy
PI only	489(52)
IMiDs only	105(11.2)
PI/IMiDs combination	276(29.3)
Other	71(7.5)
No. of lines of therapy-median(range)	1(1–9)
ASCT	133(14.1)

Abbreviations: Cr, creatinine; LDH, lactate dehydrogenase; ALB, albumin; β2-MG,β2-microglobulin; Hb, Hemoglobin; Ca, calcium; EMD, Extramedullary disease; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ISS, International Staging System; R-ISS, Revised International Staging System; PI, proteasome inhibitor; IMiDs, immunomodulatory drugs; ASCT, autologous stem cell transplantation.

Characteristics of patients with extreme survivals

According to the criteria mentioned above, 56 patients were assigned to the LR group and 82 patients in the RP group. Baseline demographic and laboratory values, separated by survival groups, are presented in Table 2. The median age in the RP group was higher than MM patients in the LR group (63 vs. 57.5, P < 0.01). There were more male patients in the RP group (64.6 vs. 46.4%, P < 0.05). Patients in the RP group had a higher percentage of renal insufficiency 34.2 vs. 17.9% (P < 0.05). Consistent differences were shown in anemia and hypercalcemia 68.3 vs. 48.2% and 23.5 vs. 7.4%, respectively (P < 0.05, P < 0.01). The discrepancy in patients with EMD between the two groups also reached statistical significance with 37.8% of patients in the RP group compared to 22.7% of patients in the LR group (P < 0.001). The occurrence of bone lesions at diagnosis was similar between the two groups (88.8 vs 85.7%, P = 0.52). There was a phenomenon showing more poor performance status patients in the RP group compared to the LR group with ECOG PS > 2 (13.4 vs 1.8%, P < 0.05).

Table 2. Demographics and clinical data of NDMM patients in two groups.

Variable	RP	LR	P value
	n/N (%)	n/N (%)
Median age, years(range)	63 (38–85)	57.5 (34–81)	<0.01
≤65	47 (57.3)	42 (75)	<0.05
66–80	32 (39)	13 (23.2)
>80	3 (3.7)	1 (1.8)
Male	53 (64.6)	26 (46.4)	<0.05
M-protein type			0.22
IgG	36 (43.9)	32 (57.1)
IgA	26 (31.7)	10 (17.9)
Light chain	13 (15.9)	7 (12.5)
Other	7 (8.5)	7 (12.5)
Cr > 2 mg/dl	28/82 (34.2)	10/56 (17.9)	<0.05
LDH increased	28/81 (34.6)	6/50 (12)	<0.001
ALB ≥ 3.5 g/dl	38/82 (46.3)	29/54 (53.7)	0.19
β2-MG ≥ 5.5 mg/L	46/80 (57.5)	19/55 (34.5)	<0.05
Hb < 100 g/L	56/82 (68.3)	27/56 (48.2)	<0.05
Ca > 11 mg/dl	19/81 (23.5)	4/54 (7.4)	<0.01
EMD	31/82 (37.8)	10/44 (22.7)	<0.001
Bone lesion	71/80 (88.8)	48/56 (85.7)	0.52
ECOG PS > 2	11/82(13.4)	1/56 (1.8)	<0.05

Abbreviations: Cr, creatinine; LDH, lactate dehydrogenase; ALB, albumin; β2-MG,β2-microglobulin; Hb, Hemoglobin; Ca, calcium; EMD, Extramedullary disease; ECOG PS, Eastern Cooperative Oncology Group Performance Status.

The cytogenetic abnormality between groups

Cytogenetic abnormalities of the study group assessed by FISH are outlined in Table 3. Among patients who tested for listed items were available, they were detected at a similar frequency in the del(17p) (22.4 vs 14.3%, P = 0.37) and del(13q) (59.6 vs. 48.1%, P = 0.37). However, patients in the RP group were less likely to harbor t(11;14) compared with those in the LR group (17.8 vs. 20%, P < 0.001). In the RP group, 21/46(45.7%) patients had high-risk cytogenetics.

Table 3. FISH results of cytogenetics.

Variable	RP	LR	P value
	n/N (%)	n/N (%)
IgH translocations
t(4;14)	14/46 (30.4)	0/9	<0.001
t(14;16)	1/46 (2.2)	0/9	<0.001
t(11;14)	8/45 (17.8)	2/10 (20)	<0.001
Secondary abnormalities
1q gain/amplification	33/46 (71.7)	4/12 (33.3)	<0.001
del(17p)	11/49 (22.4)	4/28 (14.3)	0.37
del(13q)	28/47 (59.6)	13/27 (48.1)	0.37
High-risk cytogenetics^a	21/46 (45.7)	4/9 (44.4)	<0.001

^a Patients with t(4;14), and/or t(14;16), and/or del(17) were considered at high risk.

Risk stratification based on the ISS

Two versions of ISS were adopted to predict prognosis in MM patients. These details are all illustrated in Figure 2. In the RP group, among patients who were evaluated for ISS(80/82), based on the definition, 12 (15%), 22 (28%), and 46 (58%) patients had stage I, II, and III disease, respectively. Regarding the R-ISS stage which was available for 69 patients, 42% of patients were stratified as poor prognosis patients (R-ISS > II; n = 29). We can tell that 6 patients stayed in stage I all along between different revisions of ISS. In another way, 29 patients were distributed in an advanced stage of the disease (ISS/R-ISS = III) all the time. Next, we focus on patients in the LR group. Surprisingly, relatively most patients were found in ISS stage III (19/53, 36%), and 19% of patients were stratified in R-ISS III. It was noteworthy that 6 patients were always in stage III between different risk-scoring systems (ISS/R-ISS III = 6).

Figure 2. The migration and distribution of MM patients between ISS and R-ISS in the RP (A) and LR (B) groups. ISS, International Staging System and R-ISS, Revised International Staging System.

Treatment variability in selected patients

Table 4 depicts the choice of therapy and responses induced in MM patients. The use of novel agents was similar between the two groups (89 vs. 83.9%, P = 0.39). The use of triplet drug combinations that act as first-line therapy was at a similar frequency in the RP (69.5%) and the LR group (69.6%) (P = 0.63). The most frequent first-line regimen administered was PI-based therapy in two groups, 61% in the RP, and 39.3% in the LR group. Patients in the LR group were more likely to receive therapy with PI and IMiD combinations than those in the RP group (33.9 vs 17.1%, P = 0.06). A significantly higher proportion of patients in the LR group versus the RP group were on maintenance therapy (69.6 vs. 7.3%, P < 0.001). The best response to first-line therapy was available for 63 patients in the RP group, and 51 patients in the LR group. Overall response rates (ORR) for patients in the LR group (100%) were superior to those in the RP group patients (58.7%), (P < 0.001). Deep responses were also different, with CR rates of 6.3% versus 68.6%, and very good partial response (VGPR) rates of 11.1% versus 15.7%, in the RP versus LR groups, respectively. This translated into a significantly different rate of ≥ VGPR in the two groups (17.5 vs. 84.3%, P < 0.001). The median time to best response (TBR) was 1.4 months (range 0.7–4.5) in the RP group, while the counterpart in the LR group was 4.6 months (range 1.1–22) (P < 0.001). Duration of best response (DBR) also differed significantly between the two groups (2.3 vs. 64.4 months, P < 0.001). We also depicted the specific TBR and DBR among different responses in 2 groups (Figure 3). There was a trend showing that patients in the LR group needed more time to reach the best response in all different response depths compared to the RP group (CR, 4 vs. 3 months, P = 0.17; VGPR, 6 vs. 1 month, P = 0 < 0.01; PR, 5 vs. 1 month, P < 0.001). An overwhelmingly extended DBR in the LR group than in the RP group shown was in CR, 64 vs. 1 month; VGPR, 63 vs. 4 months; PR, 83 vs. 2 months, P < 0.001. MM patients in the RP group needed similar time to reach the best response (TBR, 3 vs. 1 vs. 1 month, P = 0.225), survival plots showed that CR patients had inferior OS than patients who got PR or VGPR (P = 0.0013, Figure S2).

Figure 3. The median TBR, DBR, and OS in the two groups classified by responses. Patients in two groups classified by depth of response, and then the median TBR, DBR, an OS was depicted of patients in each response group.

Table 4. Treatment variability of patients in two groups.

Variable	RP	LR	P value
	n(%)	n(%)
Use of novel agents			0.39
Yes	73(89)	47(83.9)
No	9(11)	9(16.1)
Treatment			0.63
Doublet	17(20.7)	14(25)
Triplet	57(69.5)	39(69.6)
quadruplet or other	8(9.8)	3(5.4)
First-line therapy			0.06
PI only	50(61)	22(39.3)
IMiDs only	8(9.8)	6(10.7)
PI/IMiDs combination	14(17.1)	19(33.9)
Other	10(12.2)	9(16.1)
Maintenance therapy	6(7.3)	39(69.6)	<0.001
No. of lines of therapy-median (range)	1(1–8)	1(1–5)	<0.001
ASCT	6(7.3)	21(37.5)	<0.001
Response
ORR rate	58.7%	100%	<0.001
≥VGPR rate	17.5%	84.3%	<0.001
Best response to first-line therapy			<0.001
CR	4(6.3)	35(68.6)
VGPR	7(11.1)	8(15.7)
PR	26(41.3)	8(15.7)
SD + PD	26(41.3)	0
Time to best response, months	1.4(0.7–4.5)	4.6(1.1–22)	<0.001
Duration of best response, months	2.3(0.5–4.9)	64.4(43–157)	<0.001

Abbreviations: PI, proteasome inhibitor; IMiDs, immunomodulatory drugs; ASCT, autologous stem cell transplantation; ORR, overall response rate; VGPR, very good partial response; CR, complete response; PR, partial response; SD, stable disease; PD, progression disease.

Discussion

Our study conducted a retrospective analysis of real-world treatment patterns and outcomes in newly diagnosed MM patients in China. Two distinct groups of MM patients with extreme survivals were comprehensively depicted in clinical characteristics, treatment profiles and outcomes. Notably, this study is the first to specifically investigate MM patients with survival rates that deviate from the median range. As a result, several unexpected observations, which were inconsistent with established guidelines, were discovered. These findings further emphasize the necessity to modify the current management approach for MM and advocate for the implementation of more precise individual treatment paradigms in clinical practice.

This study retrospectively reviewed NDMM patients in a single center across nearly three decades. Then we identified two unique groups of patients. One was named the LR group which had PFS ≥ 60 months including 56 patients, another RP group incorporated 82 patients with PFS ≤ 6 months. The PFS of NDMM patients has prolonged quite a lot over the past years. In patients treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy, a long-term follow-up study showed that the median PFS was 65 months [11]. A meta-analysis showed that NDMM patients received ASCT followed by lenalidomide maintenance with a median PFS of 52.8 months [20]. This excellent PFS was derived from standard clinical interventions and selected populations, so it cannot represent the actual status in real-world settings. Population-based HAematological Registry for Observational Studies (PHAROS), a real-world data research, indicated that NDMM patients had a median PFS of 18 months [21]. In Czech, 16.3 months of median PFS was shown in the analysis of data from the Registry of Monoclonal Gammopathies (RMG) [22]. Analyses of real-world patients in multicenter China demonstrated a median PFS of 26 months [23]. Another study focused on MM patients who were not eligible for transplantation found that median PFS was 15.3 months [24]. As in our cohort, with the diversity of patients and multiple treatment patterns, the median PFS was 33.9 months, so PFS ≥ 60 months seems to be the rationale for identifying some long-term remission patients. As for patients in the RP group, in which PFS ≤ 6 months, 55 deaths and 27 progression events were recorded. The majority of patients in this group underwent early death [25,26]. Across studies, the incidences of MM patients who died within 6 months range from 13 to 22% [25,27,28]. In our cohort, early death was noted in 6.1%. The rest patients in this group had a DBR of less than 6 months, transient remission to first-line therapy predicted inferior survival of MM patients [29,30]. Therefore, these two groups of patients represent special samples in real-world practice.

The presentation and distribution of several demographic and clinical features between the two groups were far more different, which is consistent with current knowledge of MM (Table 2). Such high-risk factors including elderly patients, anemia, hypercalcemia, and renal insufficiency were more common in the RP part. However, we found some similar patients had bone lesions at diagnosis in two special groups (88.8 vs. 85.7%, P = 0.52). Nearly 70% to 80% of NDMM patients have bone lesions at the time of diagnosis [31,32]. Patients with bone lesions may be diagnosed as MM earlier than other subtypes and get early intervention, thus obtaining a positive effect on their outcomes [33]. In our cohort, the presence of bone lesions at baseline could not predict the outcomes of MM patients. However, multiple studies indicated more than 3 focal lesions identified by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT have an adverse impact on the prognosis of MM patients [34,35]. A risk-stratification model incorporating the number of focal lesions was developed to predict the survival of NDMM patients, which exhibited nice performance [36]. At present time, we should evaluate the degree of bone lesions in patients using a variety of equipment at diagnosis, this might offer more information for deciding on clinical practice.

Compared to the RP group, we found more patients harbor t(11;14) in the LR group (17.8 vs. 20%, P < 0.001). t(11;14) has an estimated prevalence of 15% to 24% in NDMM patients [37–39]. MM patients carrying t(11;14) are considered at standard risk in the current international guidelines [40,41]. Nevertheless, with the evolving treatment paradigm, especially adding novel agents, more studies reclassify patients with t(11;14) into intermediate risk [42–45]. The treatment regimens of 2 patients in the LR group with t(11,14) included PIs or IMiDs, so the impact of t(11,14) on the prognosis of MM patients in the era of novel agents still needs to be clarified. Risk reclassification also occurred in del(13q) when novel agents were given, which had comparable distribution between the two groups, those patients were considered as intermediate risk during old times [46,47]. However, this improvement does not apply to MM patients with del(17p) [46]. As a well-known high-risk factor in the present time, MM patients with del(17p) had a median OS of 3 years [41]. High-risk cytogenetics confer poor survival outcomes in MM patients [48]. We noticed 14.3% patients detected of del(17p) in the LR group; meanwhile, less than half of patients in the RP group had high-risk cytogenetics abnormalities. New therapy might alter the roles of each of the cytogenetics abnormalities, further indicating the limitations of current molecular cytogenetic classification. The definition of high-risk MM patients should be determined on the specific subclones harboring molecular abnormalities instead of imperious risk-stratification groups.

ISS is most widely used in the clinical to stratify MM patients for guiding treatment decision-making [49]. A revision of ISS combined disease biology (cytogenetic abnormalities and elevated lactate dehydrogenase) was introduced in 2015 [50]. Regardless of versions of ISS, 6 patients in the RP group were assigned to the standard risk part. On the other hand, 6 patients were classified as high risk consistently in the LR group, which accounted for 11%. These patients behaved out of predictions. It reminds us that besides counting on the baseline risk stratification, it is urgent to establish dynamic prognostic evaluation according to responses to therapy or the course of disease.

8(15.7%) patients in the LR group achieved PR with frontline therapy. This indicates that the residual diseases were might less malignant or the changed tumor microenvironment hinders the proliferation of myeloma cells [51]. TBR was slower in LR group patients. With the same depth of response, patients in the LR group needed more time to reach the best response. TBR might play a more critical role in predicting the survival outcomes in MM patients than the depth of response. A study showed that TBR with first-line therapy had a significant impact on survival [51]. We also found patients in the RP group, with PFS ≤ 6 months, patients who got PR had better OS than those with CR. This phenomenon further underscores the limited impact of the depth of remission on the prognosis of MM patients.

This is a retrospective study based on data from a National Medical Center in China. Our study has certain limitations, including some missed data such as LDH, due to the extensive data collection period. Additionally, we did not consider ASCT. The utilization of ASCT significantly impacts patients’ outcomes. However, due to the low percentage of ASCT utilization in our cohort and the highly uneven distribution between the two groups, we were unable to assess the role of ASCT on clinical outcomes in both groups. Lastly, as a university-affiliated hospital, the survival outcomes of patients visiting our institute may not fully reflect the survival rates of MM patients in China, and there may be a presence of selection bias. Nevertheless, our study provides valuable insights into the real-world extreme survival of MM patients, serving as a reflection of their condition.

We identified two distinct groups of NDMM patients who experienced extreme survival outcomes in real-world settings. The presence of bone lesions did not have a significant impact on the survival of MM patients. Surprisingly, MM patients initially classified as high-risk or low-risk displayed unexpected clinical outcomes. Those who achieved only a partial response (PR) exhibited prolonged disease control and extended overall survival (OS). Our findings provide unique insights into the management of MM patients in real-world scenarios, challenging conventional expectations. These findings are worthy of careful consideration and could potentially contribute to novel approaches in MM patient care.

Data availability statemant

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Ethics approval statment

The study was approved by the Institutional Review Board of the Zhongshan Hospital, Fudan University. Written consent was obtained from all patients.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the Shanghai Natural Science Foundation [grant number 22ZR1411400].