Shinshu Med J, 70⑴：29～38, 2022

Therapeutic Outcome of Lenalidomide-dexamethasone
in Patients with Relapsed or Refractory Systemic
Immunoglobulin Light Chain (AL) Amyloidosis :A Single-center Analysis and Review of the Literature
Akihiro Ueno1）, Nagaaki Katoh1）＊, Naoki Ezawa1）
Tsuneaki Yoshinaga1）, Masahide Yazaki2）3） and Yoshiki Sekijima1）
1） Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
2） Institute for Biomedical Sciences, Shinshu University3） Clinical Laboratory Sciences Division, Shinshu University Graduate School of Medicine

Objective : To report the safety and efficacy of the lenalidomide-dexamethasone (Rd) regimen for previously
treated patients with immunoglobulin light chain (AL) amyloidosis patients in a real-world clinical practice setting
at a single amyloidosis center in Japan.
Methods : Clinical data about patient background characteristics and treatment outcomes of patients with previ­
ously treated systemic AL amyloidosis who received Rd as salvage treatment at our department were retro­
spectively collected and analyzed.
Patients : Among the total of 262 AL amyloidosis patients in a single institute, 22 patients who were treated with
the Rd regimen between September 2001 and December 2019 after one or more preceding chemotherapeutic
regimens fulfilled the inclusion criteria.
Results : The median follow-up period was 41 (range 1-68) months. The median number of previous treatment
regimens was 2 (range 1-4). The numbers of patients who achieved complete response, very good partial response,
partial response, and no response were 14 (64 ％), 0 (0 ％), 2 (9 ％), and 6 (27 ％), respectively. Eight patients (36 ％)experienced grade ≥ 3 adverse events. Toxicity-related treatment discontinuation occurred in four patients (18 ％).
No treatment-related mortality occurred. Four patients died during the observation period, three of whom died
due to disease progression. The median overall survival has not yet been reached.
Conclusion : In this study, Rd was shown to be a safe and efficient treatment option for AL amyloidosis patients
who were refractory to first-line therapy. These results provide an important insight for clinicians treating AL
amyloidosis patients in a real-world clinical practice setting. Shinshu Med J 70 : 29―38, 2022
(Received for publication August 19, 2021 ; accepted in revised form September 8, 2021)
Key words : dexamethasone, immunoglobulin light chain (AL) amyloidosis, lenalidomide,
relapsed/refractory patients, treatment

Ⅰ Introduction
Systemic immunoglobulin light chain (AL) amyloi­

dosis is one of the major types of systemic amyloido­
sis caused by pathogenic plasma cell clones in thebone marrow. These clonal cells produce aberrant
light chains in an unregulated manner, which＊

Corresponding author : Nagaaki Katoh
Department of Medicine (Neurology and Rheumatology),
Shinshu University School of Medicine, 3-1-1
Asahi, Matsumoto, Nagano 390-8621, Japan
E-mail : nagaaki@shinshu-u.ac.jp

No. 1, 2022

accumulate and are deposited as amyloid fibrils in
multiple vital organs, such as the kidney, heart, andliver, where they cause serious functional damage1）-3）.
Therefore, the fundamental treatment strategy for29

Ueno・Katoh・Ezawa et al.

AL amyloidosis involves eliminating these culprit

derived amyloid deposition confirmed by immunohis­

plasma cell clones using chemotherapeutic agents. In

tology13） and/or mass spectrometry14）with evidence

1998, high-dose melphalan with stem cell transplan­of an underlying monoclonal plasma cell population,tation (HDM) was first reported to be effective forsuch as positive immunofixation test for M protein

AL amyloidosis4）, and is now considered one of theand/or abnormal elevation of serum free light chain

5）
6）

first-line treatment options. Recently, new chemo­

therapeutic drugs with a novel antineoplastic mecha­(FLC) and/or abnormal plasma cell population in thebone marrow on flow cytometric analysis.

nism of action, the proteasome inhibitors (PI), have

Patients who were treated with Rd after one or

emerged and are now considered as major options inmore preceding chemotherapeutic regimens were5）

the treatment of AL amyloidosis . Bortezomib is a PI

retrospectively enrolled in this study. Those whothat was first reported to provide good treatment

were receiving ongoing Rd treatment without con­7）

firmed best hematological response at the time ofoutcomes in patients with AL amyloidosis in 2007 ,3）

and it has been widely adopted in Japan and aroundregistration were excluded. Patients with low involved

the world5）. In a recent study, we demonstrated its

FLC (iFLC) titer (＜100 mg/L), referred to as patients

favorable efficacy in AL amyloidosis, including 65 ％with hematologically “unmeasurable” disease9）, wereof untreated newly diagnosed patients8）. However,also included in this study because the majority ofa proportion of patients do not respond to thesepreviously treated patients had a decreased FLC level

front-line therapies or subsequently relapse, and it

due to prior chemotherapy.

is therefore very important to investigate salvage

For evaluation of patient backgrounds, the interna­

treatment options for those who have relapsed ortional consensus guidelines from the 10th Interna­

have refractory AL amyloidosis. Lenalidomide is one

tional Symposium on Amyloidosis15） and Mayo Clinicof the immunomodulatory drugs (IMiDs) that was

staging system 201216） were used to determine organ

shown to have efficacy in relapsed/refractory AL

involvement and clinical stage, respectively.

amyloidosis patients combined with dexamethasone

Ｂ

Treatment9）-11）.

The regimen consisted of several cycles of lenalid­

However, the efficacy of Rd has not been describedomide at a dose of 20 mg/day or less for 21 days fol­in detail outside of clinical trials, with only one

lowed by 7 days of rest with dexamethasone at 40

12）

retrospective observational study in the literature ,mg/day or less on days 1-4 and 15-189）. Both wereso it is important to clarify the actual availability ofgiven orally. Drug doses were determined by the at­

the Rd regimen in actual clinical practice. Here, we

tending physician based on tolerance. The standard

report the safety and efficacy of the Rd regimen forstarting dose of lenalidomide at our center was 5

previously treated AL patients in a real-world clinicalmg/day (a lower dose was applied in patients underpractice setting at a single amyloidosis center indialysis) and then increased up to the maximum tol­

Japan. A literature review and comparison between

erable dose ≤ 20 mg/day. Dexamethasone was started

previous reports and this study were also carried out.

at a dose of 40 mg/day (20 mg/day or less in elderly(Rd regimen) in three prospective clinical trials

Ⅱ
Ａ

Patients and Methods

Patients
A total of 262 patients with systemic AL amyloido­

patients (approximately more than 70 years old)) anddecreased down to the tolerable dose. Patients re­ceived prophylaxis with low-dose aspirin (100 mg/day) and proton pump inhibitor.

sis were identified in a series of medical records ofTreatment cycles were continued until confirma­

our department between September 2001 and De­tion of best hematological response. If complete he­cember 2019 at the Shinshu University School of

matological response (CR) was achieved, several

Medicine, Matsumoto, Japan. Diagnosis of systemic

cycles (0-6 cycles) were added for consolidation if

AL amyloidosis was made based on light chain-tolerated. Rd treatment was discontinued upon severe

30

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l. 70

Rd therapy for AL amyloidosis
Table 1

Clinical backgrounds of 22 patients at baseline

Variable
Value
Median age, years (range)
64.5 (48-82)
Number of male/female patients
10 / 12
Clonal subtype of cases, κ/λ, number (％)
6 (27.3) / 16 (72.7)
Number of cases previously treated (％)
22 (100.0)
Median number of previous treatment regimens (range)
2.0 (1-4)
Details of prior regimens, number of cases (％)
Bortezomib and dexamethasone
21 (95.5)
Melphalan and dexamethasone
11 (50.0)
High-dose melphalan with stem cell transplantation
3 (13.6)
Vincristine, doxorubicin and dexamethasone
3 (13.6)
Lenalidomide or pomalidomide based regimen
0 (0.0)Thalidomide
1 (4.5)High dose dexamethasone
1 (4.5)Median NYHA class (range)
1.0 (0-3)
Median ECOG performance status (range)
0.0 (0-3)
Mayo stage 2012, number of cases (％)Ⅰ
8 (36.4)Ⅱ
5 (22.7)Ⅲ
8 (36.4)Ⅳ
1 (4.5)Median dFLC, mg/L (range)
17.8 (2.60-506.92)
Median TnT, ng/mL (range)
0.041 (0.004-0.586)
Median NT-proBNP, pg/mL (range)
1584.0 (59.1-16203.0)
Organ involvement, number of cases (％)
Heart
13 (59.1)
Kidney18 (81.8)
Liver
6 (27.3)
Gastrointestinal tract
4 (18.2)
Peripheral nerve
2 (9.1)
Median of mean left ventricular wall thickness, cm (range)
1.45 (0.76-2.10)
Median left ventricular ejection fraction, ％ (range)
74.1 (44.4-88.9)
Median serum creatinine level, mg/dL (range)
1.01 (0.49-8.72)
The number of patients with advanced renal failure requiring dialysis (％)
2 (9.1)
Median urine protein/creatinine ratio, g/gCr (range)
3.08 (0-18.88)
Median total bilirubin level, mg/dL (range)
0.51 (0.26-2.31)
Median alkaline phosphatase level, IU/L (range)
303.5 (96-1794)
NYHA New York Heart Association, ECOG Eastern Cooperative Oncology Group
dFLC difference between involved and uninvolved free light chain, TnT troponin T
NT-proBNP N-terminal of the prohormone brain natriuretic peptide

adverse events or evidence of failure to response de­

FLC levels (so-called “unmeasurable” patients). For

termined by continuous elevation or sustained nadir

example, those with a decreased dFLC level＜40of iFLC before achieving CR.

mg/L at the Rd treatment baseline are unsuitable toＣdetermine a VGPR response. Therefore, we applied

Outcome evaluation
Hematological response was classified into four

modified criteria as follows. If the baseline iFLC level

levels according to the international consensus guide­was ≥ 50 mg/L and＜100 mg/L, VGPR was not de­lines, i.e., complete response (CR, normal FLC ratio

fined for those patients and only the CR, PR, or NR

with negative serum and urine immunofixation), very

classification was applied. If the baseline iFLC level

good partial response (VGPR, difference between in­

was＜50 mg/L, VGPR and PR were not defined forvolved and uninvolved FLCs (dFLC)＜40 mg/L), par­those patients and only the CR or NR classification

tial response (PR, dFLC decrease＞50 ％), and no re­

was applied.

17）

sponse (NR) . However, these criteria are difficult toSome patients were treated with a second Rd regi­

apply simply to previously treated patients with low

men when they relapsed after completing the first

No. 1, 2022

31

Ueno・Katoh・Ezawa et al.

Fig. 1 Clinical courses of enrolled patients
Each bar represents an individual patient. The bar length indicates follow-up period. The meaningsof symbols and colors of bars are indicated in the inset. A total of 22 patients are shown. Hematologicalresponse of each patient is presented on the bar.

Rd treatment. The results of hematological response

inclusion criteria. The median number of previous

for the second Rd regimen were excluded from cal­treatment regimens was 2 (range 1-4). The mostculating the best hematological response rate.

commonly used regimen before Rd was bortezomib-

Adverse events were determined and graded inbased therapy (bortezomib-dexamethasone)8） (21

accordance with the Common Terminology Criteria

patients, 96 ％). Three patients (14 ％) were treatedfor Adverse Events (CTCAE) version 4.0-JCOG.

with HDM. There were no patients who had been

Treatment-related mortality (TRM) was defined aspreviously exposed to IMiDs with the exception ofearly death within 100 days after initiation of treat­one patient who had been treated with thalidomide

ment. Survival was evaluated by the Kaplan -Meier(Pt21, Fig. 1). The most commonly involved organ

method.

was the kidney (18 patients, 82 ％) and two patients
Ⅲ

Ａ

Results

Patient background

had advanced renal failure requiring dialysis (Pt14
and 16, Fig. 1). Thirteen patients (59 ％) had cardiac
involvement and the median NYHA class was 1

A total of 22 patients fulfilled the inclusion criteria(range 0-3), including three patients with NYHA

and were enrolled in this study. The clinical back­class 3 (Pt04, 08, and 17, Fig. 1). According to thegrounds of these 22 patients at the Rd initiation

Mayo staging system 201216）, 13 patients (59 ％) werebaseline are summarized in Table 1. The median age

classified as less than stage III and there was onlyof the patients was 64.5 (range 48-82) years. All pa­

one patient with stage IV disease (Pt13, Fig. 1). The

tients had a prior treatment history as part of themedian iFLC and dFLC levels were 36.8 (range 12.2-

32

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l. 70

Rd therapy for AL amyloidosis
Table 2Treatment details and outcomes

Parameter
Median follow-up period, months (range)
Lenalidomide dose
Median initiating dose, mg (range)
Median maximum dose, mg (range)
Median ending dose, mg (range)
Dexamethasone dose
Median initiating dose, mg (range)
Median ending dose, mg (range)
Median number of total Rd treatment cycles (range)
Best hematological response, number (％)
CR
VGPR
PR
NR
Median number of cycles needed to achieve ≥ PR (range), n＝16Median number of cycles needed to achieve CR (range), n＝14Median number of consolidation treatment cycles after achieving CR (range), n＝14
Recurrence
Recurrence among those achieving CR, number (recurrence rate, ％), n＝14Median duration from achieving CR to recurrence, months (range), n＝5
Tolerance
The number of patients who discontinued Rd treatment due to toxicity (％)
Treatment-related mortality, number (％)
CR complete response, VGPR very good partial response, PR partial response, NR no response
Rd lenalidomide and dexamethasone
Table 3was notable that most of the patients (19 patients,ease with a decreased level of iFLC＜100 mg/L.
Ｂ

Treatment details
The treatment details are summarized in Table 2

and Fig. 1. The median initial, maximum, and ending
doses of lenalidomide were 5.0 (range 2.5-5.0) mg,
10.0 (range 2.5-20) mg, and 7.5 (range 0.71-20) mg,
respectively. The median initial and ending doses ofdexamethasone were 40 (range 8-40) mg and 20(range 0-40) mg, respectively. The median number ofcycles needed to achieve hematological response (PRor better) and CR were 1 (range 1-7) and 2 (range
1-12), respectively. The median number of consolida­tion treatment cycles after achieving CR (n＝14) was
4 (range 0-6).

5.0 (2.5-5.0)
10.0 (2.5-20)
7.5 (0.71-20)
40 (8-40)
20 (0-40)
6.5 (1-18)
14 (63.6)
0 (0.0)2 (9.1)
6 (27.3)
1 (1-7)
2 (1-12)4 (0-6)5 (35.7)
12 (2-35)
4 (18.2)
0 (0.0)Adverse events

516.0) and 17.8 (range 2.6-506.9) mg/L, respectively. It
86 ％) were classified as having “unmeasurable” dis­Value
41 (1-68)

Adverse event
Thrombocytopenia
Fatigue
Edema
Rash＊
Dysgeusia
Anorexia
Muscle cramp
Peripheral sensory neuropathy
Respiratory infection
Urinary tract infection
Elevated creatinine level
Elevated AST and/or ALT level
Elevated alkaline phosphatase level

Number ofcases (n＝22)
Grade
1 2 3 4
0
0
1
0
2
2
3
0
0
0
1
0
2
1
3
0
0
4
0
0
1
0
0
0
0
3
0
0
3
1
1
0
0
2
0
0
0
1
0
0
1
2
0
0
1
0
1
0
0
1
0
0

AST aspartate aminotransferase,
ALT alanine aminotransferase＊

Including 1 case of Stevens-Johnson syndrome, Grade 3

ＣOutcomesor NR were 14 (64 ％), 0 (0 ％), 2 (9 ％), and 6 (27 ％),１

Hematological response

respectively.

Treatment responses are summarized in Table 2

２

Safetyand Fig. 1. Hematological response (PR or better)

Adverse events possibly related to treatment andwas observed in 16 patients (73 ％ ). In detail, thetheir grades are summarized in Table 3. The num­

numbers of patients who achieved CR, VGPR, PR,bers of patients with grade ≥ 3 adverse events were

No. 1, 2022

33

Ueno・Katoh・Ezawa et al.

Fig. 2 Overall survival
The overall survival curve of 22
enrolled patients is shown (KaplanMeier method). Median overall sur­vival has not yet been reached.

as follows : peripheral sensory neuropathy (n＝1),

All five patients with relapse received re-treatment

edema (n＝1), rash (n＝3), thrombocytopenia (n＝1),

with Rd (Pt 07, 10, 17, 18, and 21, Fig. 1). It is note­fatigue (n＝3), and transaminase elevation (n＝1). Rd

worthy that all except one of these patients achieved

therapy was discontinued due to toxicity in four pa­

CR again ; the patient who did not achieve CR again

tients (18 ％, Pt01, 10, 17, and 22, Fig. 1). The detailed(Pt07) was receiving ongoing Rd treatment without

reasons for discontinuation in these four patients

confirmed hematological response at the time of eval­

were as follows : Stevens-Johnson syndrome (grade

uation (Fig. 1).

3) in Pt01, elevation of AST (grade 3), ALT (grade 3),

５Survivaland ALP (grade 2) in Pt10, deterioration of amyloid

Four patients (Pt02, 08, 17, and 22, Fig. 1) diedneuropathy (grade 3) in Pt17 (first discontinuation),

during the observation period. Three were due tofatigue (grade 3) and neuropathic pain (grade 3) indisease progression (Pt02, 08, and 22) and the other

Pt17 (second discontinuation), and elevation of

was due to amyloidosis-unrelated disease progression

creatinine (grade 2) in Pt22. There were no cases of(Pt22). The overall survival is shown in Fig. 2. The

treatment-related death within 100 days after Rd

median overall survival has not yet been reached.

initiation in this study (0 patients, 0 ％).
３

RecurrenceⅣ

Discussion

Among the patients who achieved CR (n＝14), he­Thalidomide and its analogs, lenalidomide and po­

matological relapse (dropping out from the CR crite­

malidomide, are IMiDs that have been reported torion) occurred in five patients (36 ％ ) during thehave multiple actions with direct and/or indirect an­

follow-up period (Fig. 1, Table 2). The median dura­

titumor effects18）19）. Compared to thalidomide, twotion from achieving CR to relapse was 12 (range

novel IMiDs, lenalidomide and pomalidomide, were2-35) months. The mean number of consolidation

reported to have potent anticancer activities and bet­

treatment cycles in the patients with relapse (2, range

ter tolerability profiles18）19）. Among these IMiDs,

0-3, n＝5) tended to be lower than that in the patientslenalidomide has been studied most extensively andwithout relapse (4.2, range 2-6, n＝9) (P＝0.058).

is approved for treatment of patients with multiple

Therefore, if tolerated, at least four cycles of consoli­

myeloma (MM)19）. The dual actions of lenalidomide,

dation treatment are recommended to prevent futurei.e., direct tumoricidal activity and immunomodulato­

relapse.

ry effects, have been investigated and are now con­４

sidered important underlying mechanisms of the fa­

Re-treatment
34

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l. 70

Rd therapy for AL amyloidosis

vorable effect of this drug. The tumoricidal activities

three previous studies9）-11） are not suitable to assess

include disrupting stromal support of abnormal plas­

the treatment response in detail because the criteria

macytes, upregulating tumor suppressor genes, in­lack a VGPR grade. Therefore, the results of hemato­

ducing cell cycle arrest, and activating direct tumor

logical response in these studies could not be simply

cell apoptosis. The immunomodulatory effects include

compared with current data. This study and a report＋

T cell cytolysis,

from the UK12） are the only two reports to date eval­increasing NK cell expression of death effector mole­uating the performance of the Rd regimen for AL

cules, stimulating T cell proliferation and IFN-γ andamyloidosis using the updated hematological response

IL-2 production, and reducing histone methylation

criteria17）. Taken together, the patient backgrounds

and increasing histone acetylation at the p21 promot­

and manner of hematological response evaluation inenhancing antigen-specific CD8

18）
19）

this study are highly consistent with the current real-

However, the number of previous reports describ­world practice setting compared to previous studies,ing the efficacy of lenalidomide against AL amyloido­

and therefore provide important information for clini­

sis is very limited. There have been only four reports

cians in current clinical practice.

er.

(three clinical trials and one observational study) to

Another notable feature of this study is that we

9）
-12）

.

achieved a better hematological response rate thanThis is therefore only the second report describing

previous reports (Table 4). For example, the CR rate

the results of the Rd regimen in a retrospective study

in this study was 64 ％ compared to 0 ％ -29 ％ in

and is also the first report in an Asian cohort. Table 4other reports, and the NR rate in this study waspresents a summary and comparison of these previ­

27 ％ compared to 33 ％-59 ％ in the other reports.

ous reports and the present study.

The increased levels of iFLC in previous reports

date regarding the Rd regimen in AL amyloidosis

One of the notable features of this study was that

(Table 4) may have been responsible for their limited

the study design was highly consistent with thetreatment outcomes because elevated dFLC (andreal-world clinical practice setting in two respects.

therefore iFLC) is known to be a major correlate ofFirst, patient backgrounds corresponded to thosedisease severity16）. As described above, patients withseen in clinical practice. Second, the treatment out­

“unmeasurable” disease with a decreased level ofcome evaluation criteria were updated. The patient

iFLC9） were excluded from previous studies, and sobackgrounds are often affected by the study design.

only those with higher titer iFLC were included.

Prospective clinical trials generally require some spe­

A better outcome with regard to safety is also an­cial inclusion and/or exclusion criteria and special

other feature of our study (Table 4). In terms of sal­treatment protocols to achieve a certain study pur­vage therapy, rapid response is not as important as

pose. For example, patients with “unmeasurable”

in first-line therapy because the dFLC level would

9）

disease with a decreased level of iFLC were excluded

be already suppressed to some extent in most cases

from previous studies because of the use of hemato­

due to prior chemotherapy. Therefore, it is more im­

logical response criteria, which required a “measurable”

portant to continue the treatment safely until achiev­

15）

iFLC level to determine hematological response .

ing CR without dropping out. Hence, the minimum-

Therefore, only those with higher titer iFLC weredose starting method may be a suitable treatment

included in these previous studies. Therefore, this is

option. In the present study, lenalidomide was started

the first report actively including patients with he­at the minimum dose and then increased if tolerated

matologically “unmeasurable” disease who are com­to avoid the rapid emergence of severe adverse ef­

mon targets of salvage therapy in current clinicalfects. In contrast, all of the previous studies begansettings but have been excluded from studies in thelenalidomide with the maximum dose and then re­past (Table 4). The method of treatment outcome

duced the dose if it was not well tolerated (Table 4).

evaluation is important. The old criteria used in the

Compared to the previous studies, the incidences ofNo. 1, 202235

1 (0-3)Median number of previous treatment regimens (range)

4 (18.2)
4 (18.2)

Number of patients who discontinued treatment due to toxicity

Treatment-related mortality (early deaths), number (％)＜2 (ND)

13 (59.0)

9 (40.9)

0 (0.0)n＝22

Old criteria [15]4 (1-14)

Reduced if untolerated15

18 (75.0)

16 (66.7)

ND

ND

19 (79.2)

7 (29.2)

17 (70.8)

24 (100.0)

3 (2-5)

Excluded from evaluation

Prospective

Semi-clinical trial

Palladini (Pavia),
2012 [11]3 (1-19).

33 (39)51 (61)

17 (20)n＝84

New criteria [17]6.5 (1-52)

Reduced if untolerated25

52 (61.9)

42 (50)1034 (110-79576)

109.5 (19.5-1480)

64 (76.1)

13 (15.5)

ND

58 (69)2 (1-6)ND

Retrospective

Observational study

Mahmood (London),2014 [12]1 (1-7)6 (27.3)

16 (72.7)

14 (63.6)

n＝22

New criteria [17]6.5 (1-18)

Increased if tolerated

5

18 (81.8)

13 (59.1)

876.9 (59.1-13529.0)

54.2 (12.2-516.0)

1 (4.5)

3 (13.6)

11 (50.0)

21 (95.5)

2 (1-4)

Included

Retrospective

Observational study

This study (Shinshu)

ND

ND

1 (2.9)11 (32.4)

14

2 (8.3)ND

not reached

ND

ND

23 (27)

not reached

0 (0.0)4 (18.2)

8 (36.4)l. 70

12 (50.0)

Shinshu Med J

NDMedian survival, months

19 (86.4)

Number of patients who experienced grade ≥ 3 adverse event

6 (3-6)8 (33.3)

6.2 (ND)

13 (59.0)

7 (29.2)
16 (66.7)ND
9 (40.9)n＝24

Old criteria [15]6 (0-23)

Reduced if untolerated25

13 (38.2)

13 (38.2)

ND

ND

7 (20.6)

19 (55.9)

ND

ND

1 (0-5)ND

Prospective

Clinical trial

Sanchorawala (Boston),
2007 [10]n＝22Old criteria [15]ND

Reduced if untolerated

Median number of cycles needed to achieve ≥ PR (range)NR

PR or better (positive “hematologic response” on old criteria [15])CR

Hematological response, number (％)

Applied hematological response criteria

Median number of total treatment cycles (range)

Lenalidomide dose adjusting manner25

16 (72.7)

KidneyStandard starting dose of lenalidomide, mg

14 (63.6)

Heart

Organ involvement, number (％)

196 (22.6-7050)
1324.5 (109-42844)

Median NT-proBNP, pg/mL (range)

ND

Median involved FLC, mg/L (range)

Thalidomide based

6 (27.3)

ND

Melphalan and dexamethasone

High-dose melphalan with stem cell transplantation

ND

Bortezomib and dexamethasone

Type of previous treatment, number (％)

ExcludedPatients with hematologically “unmeasurable” disease

Prospective＊

Clinical trial

Type of study

Dispenzieri (Mayo),2007 [9]Summary and comparison of previous reports and this study

FLC free light chain, NT-proBNP N-terminal of the prohormone brain natriuretic peptide, CR complete response, PR partial response, NR no response, ND not described＊
Patients WITHOUT serum monoclonal protein greater than or equal to 10 g/L (1.0 g/dL) by protein electrophoresis OR more than 200 mg monoclonal protein in the urine on 24-hourelectrophoresis OR serum FLC greater than or equal to 100 mg/L along with an abnormal FLC κ/λ ratio were defined as hematologically “unmeasurable” disease [9].

36

Study design

Table 4

Ueno・Katoh・Ezawa et al.

Rd therapy for AL amyloidosis

severe adverse events, toxicity-related treatment dis­families for their contributions.

continuation, and early death were lower in ourCompliance with Ethical Standards

study (Table 4). Therefore, it is suggested that thesafer profiles in our study may have been attributable

Ethicsto this careful treatment protocol. Starting with the

All procedures in studies involving human partici­

maximum dose of lenalidomide (25 mg) may not be

pants were performed in accordance with the ethicalsafe for some patients. Notably, although lenalidomide

standards of the institutional and/or national research

was initiated from the minimum dose in our study,committee and with the 1964 Declaration of Helsinki

the speed at which hematological response (PR or

and its later amendments or comparable ethical stan­better) was achieved was equivalent to or faster thandards. Written informed consent for receiving Rd

that in previous reports (Table 4).

treatment was obtained from all enrolled patients.

In conclusion, our study provided important insightThis study protocol was approved by the Ethics

for clinicians treating AL patients in the real world

Committee of Shinshu University School of Medicine

because patient backgrounds and updated evaluation(No. 3988).

criteria were highly consistent with current clinical

Conflict of Interest

practice settings. The Rd regimen used in this study
was sufficiently safe and effective for patients withrelapsed and/or refractory AL amyloidosis. The de­

The authors declare that they have no conflicts ofinterest.

creased level of iFLC and safer treatment protocol

Funding

were thought to be responsible for these outcomes.

This study was supported by a grant from the

Acknowledgments

Amyloidosis Research Committee, the Ministry of

The authors are grateful to the patients and theirHealth, Labour and Welfare, Japan

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